Publications

2020

  • Ostafe, R., Fontaine, N., Frank, D., Ng Fuk Chong, M., Prodanovic, R., Pandjaitan, R., Offman, B., Cadet, F., & Fischer, R.. (2020). One-shot optimization of multiple enzyme parameters: tailoring glucose oxidase for ph and electron mediators. Biotechnol bioeng, 117(1), 17-29. doi:10.1002/bit.27169
    [BibTeX] [Abstract]

    Enzymes are biological catalysts with many industrial applications, but natural enzymes are usually unsuitable for industrial processes because they are not optimized for the process conditions. The properties of enzymes can be improved by directed evolution, which involves multiple rounds of mutagenesis and screening. By using mathematical models to predict the structure-activity relationship of an enzyme, and by defining the optimal combination of mutations in silico, we can significantly reduce the number of bench experiments needed, and hence the time and investment required to develop an optimized product. Here, we applied our innovative sequence-activity relationship methodology (innov’sAR) to improve glucose oxidase activity in the presence of different mediators across a range of pH values. Using this machine learning approach, a predictive model was developed and the optimal combination of mutations was determined, leading to a glucose oxidase mutant (P1) with greater specificity for the mediators ferrocene-methanol (12-fold) and nitrosoaniline (8-fold), compared to the wild-type enzyme, and better performance in three pH-adjusted buffers. The kcat /KM ratio of P1 increased by up to 121 folds compared to the wild type enzyme at pH 5.5 in the presence of ferrocene methanol.

    @article{Ostafe:2020aa,
    abstract = {Enzymes are biological catalysts with many industrial applications, but natural enzymes are usually unsuitable for industrial processes because they are not optimized for the process conditions. The properties of enzymes can be improved by directed evolution, which involves multiple rounds of mutagenesis and screening. By using mathematical models to predict the structure-activity relationship of an enzyme, and by defining the optimal combination of mutations in silico, we can significantly reduce the number of bench experiments needed, and hence the time and investment required to develop an optimized product. Here, we applied our innovative sequence-activity relationship methodology (innov'sAR) to improve glucose oxidase activity in the presence of different mediators across a range of pH values. Using this machine learning approach, a predictive model was developed and the optimal combination of mutations was determined, leading to a glucose oxidase mutant (P1) with greater specificity for the mediators ferrocene-methanol (12-fold) and nitrosoaniline (8-fold), compared to the wild-type enzyme, and better performance in three pH-adjusted buffers. The kcat /KM ratio of P1 increased by up to 121 folds compared to the wild type enzyme at pH 5.5 in the presence of ferrocene methanol.},
    author = {Ostafe, Raluca and Fontaine, Nicolas and Frank, David and Ng Fuk Chong, Matthieu and Prodanovic, Radivoje and Pandjaitan, Rudy and Offman, Bernard and Cadet, Fr{\'e}d{\'e}ric and Fischer, Rainer},
    date-added = {2019-10-12 00:51:55 +0200},
    date-modified = {2020-02-23 21:20:35 +0100},
    doi = {10.1002/bit.27169},
    journal = {Biotechnol Bioeng},
    journal-full = {Biotechnology and bioengineering},
    keywords = {artificial intelligence; directed evolution; multiple parameter improvement; protein sequence activity relationship; protein spectrum; rational screening},
    month = {January},
    number = {1},
    pages = {17-29},
    pmid = {31520472},
    title = {One-shot optimization of multiple enzyme parameters: Tailoring glucose oxidase for pH and electron mediators},
    volume = {117},
    year = {2020},
    Bdsk-Url-1 = {https://doi.org/10.1002/bit.27169}}

  • Liu, G., Xuan, N., Rajashekar, B., Arnaud, P., Offmann, B., & Picimbon, J.. (2020). Comprehensive history of csp genes: evolution, phylogenetic distribution and functions. Genes, 11(4), 413.
    [BibTeX] [Abstract]

    In this review we present the developmental, histological, evolutionary and functional properties of insect chemosensory proteins (CSPs) in insect species. CSPs are small globular proteins folded like a prism and notoriously known for their complex and arguably obscure function(s), particularly in pheromone olfaction. Here, we focus on direct functional consequences on protein function depending on duplication, expression and RNA editing. The result of our analysis is important for understanding the significance of RNA-editing on functionality of CSP genes, particularly in the brain tissue.

    @article{liu2020comprehensive,
    abstract = {In this review we present the developmental, histological, evolutionary and functional properties of insect chemosensory proteins (CSPs) in insect species. CSPs are small globular proteins folded like a prism and notoriously known for their complex and arguably obscure function(s), particularly in pheromone olfaction. Here, we focus on direct functional consequences on protein function depending on duplication, expression and RNA editing. The result of our analysis is important for understanding the significance of RNA-editing on functionality of CSP genes, particularly in the brain tissue.},
    author = {Liu, Guoxia and Xuan, Ning and Rajashekar, Balaji and Arnaud, Philippe and Offmann, Bernard and Picimbon, Jean-Fran{\c{c}}ois},
    date-added = {2020-11-25 22:16:02 +0100},
    date-modified = {2020-11-25 22:16:45 +0100},
    journal = {Genes},
    number = {4},
    pages = {413},
    publisher = {Multidisciplinary Digital Publishing Institute},
    title = {Comprehensive History of CSP Genes: Evolution, Phylogenetic Distribution and Functions},
    volume = {11},
    year = {2020}}

  • Ajjolli Nagaraja, A., Charton, P., Cadet, X. F., Fontaine, N., Delsaut, M., Wiltschi, B., Voit, A., Offmann, B., Damour, C., Grondin-Perez, B., & others. (2020). A machine learning approach for efficient selection of enzyme concentrations and its application for flux optimization. Catalysts, 10(3), 291.
    [BibTeX] [Abstract]

    The metabolic engineering of pathways has been used extensively to produce molecules of interest on an industrial scale. Methods like gene regulation or substrate channeling helped to improve the desired product yield. Cell-free systems are used to overcome the weaknesses of engineered strains. One of the challenges in a cell-free system is selecting the optimized enzyme concentration for optimal yield. Here, a machine learning approach is used to select the enzyme concentration for the upper part of glycolysis. The artificial neural network approach (ANN) is known to be inefficient in extrapolating predictions outside the box: high predicted values will bump into a sort of “glass ceiling”. In order to explore this “glass ceiling” space, we developed a new methodology named glass ceiling ANN (GC-ANN). Principal component analysis (PCA) and data classification methods are used to derive a rule for a high flux, and ANN to predict the flux through the pathway using the input data of 121 balances of four enzymes in the upper part of glycolysis. The outcomes of this study are i. in silico selection of optimum enzyme concentrations for a maximum flux through the pathway and ii. experimental in vitro validation of the “out-of-the-box” fluxes predicted using this new approach. Surprisingly, flux improvements of up to 63% were obtained. Gratifyingly, these improvements are coupled with a cost decrease of up to 25% for the assay.

    @article{ajjolli2020machine,
    abstract = {The metabolic engineering of pathways has been used extensively to produce molecules of interest on an industrial scale. Methods like gene regulation or substrate channeling helped to improve the desired product yield. Cell-free systems are used to overcome the weaknesses of engineered strains. One of the challenges in a cell-free system is selecting the optimized enzyme concentration for optimal yield. Here, a machine learning approach is used to select the enzyme concentration for the upper part of glycolysis. The artificial neural network approach (ANN) is known to be inefficient in extrapolating predictions outside the box: high predicted values will bump into a sort of ``glass ceiling''. In order to explore this ``glass ceiling'' space, we developed a new methodology named glass ceiling ANN (GC-ANN). Principal component analysis (PCA) and data classification methods are used to derive a rule for a high flux, and ANN to predict the flux through the pathway using the input data of 121 balances of four enzymes in the upper part of glycolysis. The outcomes of this study are i. in silico selection of optimum enzyme concentrations for a maximum flux through the pathway and ii. experimental in vitro validation of the ``out-of-the-box'' fluxes predicted using this new approach. Surprisingly, flux improvements of up to 63% were obtained. Gratifyingly, these improvements are coupled with a cost decrease of up to 25% for the assay.},
    author = {Ajjolli Nagaraja, Anamya and Charton, Philippe and Cadet, Xavier F and Fontaine, Nicolas and Delsaut, Mathieu and Wiltschi, Birgit and Voit, Alena and Offmann, Bernard and Damour, Cedric and Grondin-Perez, Brigitte and others},
    date-added = {2020-11-25 22:13:10 +0100},
    date-modified = {2020-11-25 22:13:38 +0100},
    journal = {Catalysts},
    number = {3},
    pages = {291},
    publisher = {Multidisciplinary Digital Publishing Institute},
    title = {A Machine Learning Approach for Efficient Selection of Enzyme Concentrations and Its Application for Flux Optimization},
    volume = {10},
    year = {2020}}

  • Dhingra, S., Sowdhamini, R., Sanejouand, Y., Cadet, F., & Offmann, B.. (2020). Customised fragment libraries for ab initio protein structure prediction using a structural alphabet. Arxiv preprint arxiv:2005.01696.
    [BibTeX] [Abstract]

    Motivation: Computational protein structure prediction has taken over the structural community in past few decades, mostly focusing on the development of Template-Free modelling (TFM) or ab initio modelling protocols. Fragment-based assembly (FBA), falls under this category and is by far the most popular approach to solve the spatial arrangements of proteins. FBA approaches usually rely on sequence based profile comparison to generate fragments from a representative structural database. Here we report the use of Protein Blocks (PBs), a structural alphabet (SA) to perform such sequence comparison and to build customised fragment libraries for TFM. Results: We demonstrate that predicted PB sequences for a query protein can be used to search for high quality fragments that overall cover above 90% of the query. The fragments generated are of minimum length of 11 residues, and fragments that cover more than 30% of the query length were often obtained. Our work shows that PBs can serve as a good way to extract structurally similar fragments from a database of representatives of non-homologous structures and of the proteins that contain less ordered regions.

    @article{dhingra2020customised,
    abstract = {Motivation: Computational protein structure prediction has taken over the structural community in past few decades, mostly focusing on the development of Template-Free modelling (TFM) or ab initio modelling protocols. Fragment-based assembly (FBA), falls under this category and is by far the most popular approach to solve the spatial arrangements of proteins. FBA approaches usually rely on sequence based profile comparison to generate fragments from a representative structural database. Here we report the use of Protein Blocks (PBs), a structural alphabet (SA) to perform such sequence comparison and to build customised fragment libraries for TFM. Results: We demonstrate that predicted PB sequences for a query protein can be used to search for high quality fragments that overall cover above 90% of the query. The fragments generated are of minimum length of 11 residues, and fragments that cover more than 30% of the query length were often obtained. Our work shows that PBs can serve as a good way to extract structurally similar fragments from a database of representatives of non-homologous structures and of the proteins that contain less ordered regions.},
    author = {Dhingra, Surbhi and Sowdhamini, Ramanathan and Sanejouand, Yves-Henri and Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard},
    date-added = {2020-11-25 22:10:34 +0100},
    date-modified = {2020-11-25 22:11:07 +0100},
    journal = {arXiv preprint arXiv:2005.01696},
    title = {Customised fragment libraries for ab initio protein structure prediction using a structural alphabet},
    year = {2020}}

  • Dhingra, S., Sowdhamini, R., Cadet, F., & Offmann, B.. (2020). A glance into the evolution of template-free protein structure prediction methodologies. Biochimie, 175, 85-92. doi:https://doi.org/10.1016/j.biochi.2020.04.026
    [BibTeX] [Abstract] [Download PDF]

    Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure refinement protocols. A tremendous success has been witnessed in template-based modelling protocols, whereas strategies that involve template-free modelling still lag behind, specifically for larger proteins (>150 a.a.). Various improvements have been observed in ab initio protein structure prediction methodologies overtime, with recent ones attributed to the usage of deep learning approaches to construct protein backbone structure from its amino acid sequence. This review highlights the major strategies undertaken for template-free modelling of protein structures while discussing few tools developed under each strategy. It will also briefly comment on the progress observed in the field of ab initio modelling of proteins over the course of time as seen through the evolution of CASP platform.

    @article{DHINGRA202085,
    abstract = {Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure refinement protocols. A tremendous success has been witnessed in template-based modelling protocols, whereas strategies that involve template-free modelling still lag behind, specifically for larger proteins (>150 a.a.). Various improvements have been observed in ab initio protein structure prediction methodologies overtime, with recent ones attributed to the usage of deep learning approaches to construct protein backbone structure from its amino acid sequence. This review highlights the major strategies undertaken for template-free modelling of protein structures while discussing few tools developed under each strategy. It will also briefly comment on the progress observed in the field of ab initio modelling of proteins over the course of time as seen through the evolution of CASP platform.},
    author = {Surbhi Dhingra and Ramanathan Sowdhamini and Fr{\'e}d{\'e}ric Cadet and Bernard Offmann},
    date-added = {2020-11-25 22:07:26 +0100},
    date-modified = {2020-11-25 22:07:26 +0100},
    doi = {https://doi.org/10.1016/j.biochi.2020.04.026},
    issn = {0300-9084},
    journal = {Biochimie},
    keywords = {Protein structure prediction, Ab initio modelling, Template-Free modelling, Artificial Intelligence},
    pages = {85 - 92},
    title = {A glance into the evolution of template-free protein structure prediction methodologies},
    url = {http://www.sciencedirect.com/science/article/pii/S0300908420300961},
    volume = {175},
    year = {2020},
    Bdsk-Url-1 = {http://www.sciencedirect.com/science/article/pii/S0300908420300961},
    Bdsk-Url-2 = {https://doi.org/10.1016/j.biochi.2020.04.026}}

  • Dhingra, S., Sowdhamini, R., Cadet, F., & Offmann, B.. (2020). A glance into the evolution of template-free protein structure prediction methodologies. Arxiv preprint arxiv:2002.06616.
    [BibTeX] [Abstract]

    Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure refinement protocols. A tremendous success has been witnessed in template-based modelling protocols, whereas strategies that involve template-free modelling still lag behind, specifically for larger proteins (> 150 aa). Various improvements have been observed in ab initio protein structure prediction methodologies overtime, with recent ones attributed to the usage of deep learning approaches to construct protein backbone structure from its amino acid sequence. This review highlights the major strategies undertaken for template-free modelling of protein structures while discussing few tools developed under each strategy. It will also briefly comment on the progress observed in the field of ab initio modelling of proteins over the course of time as observed on CASP platform.

    @article{dhingra2020glance,
    abstract = {Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure refinement protocols. A tremendous success has been witnessed in template-based modelling protocols, whereas strategies that involve template-free modelling still lag behind, specifically for larger proteins (> 150 aa). Various improvements have been observed in ab initio protein structure prediction methodologies overtime, with recent ones attributed to the usage of deep learning approaches to construct protein backbone structure from its amino acid sequence. This review highlights the major strategies undertaken for template-free modelling of protein structures while discussing few tools developed under each strategy. It will also briefly comment on the progress observed in the field of ab initio modelling of proteins over the course of time as observed on CASP platform.},
    author = {Dhingra, Surbhi and Sowdhamini, Ramanathan and Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard},
    date-added = {2020-02-23 21:14:28 +0100},
    date-modified = {2020-02-23 21:15:02 +0100},
    journal = {arXiv preprint arXiv:2002.06616},
    title = {A glance into the evolution of template-free protein structure prediction methodologies},
    year = {2020},
    Bdsk-Url-1 = {https://arxiv.org/abs/2002.06616}}

2019

  • Vetrivel, I., de Brevern, A. G., Cadet, F., Srinivasan, N., & Offmann, B.. (2019). Structural variations within proteins can be as large as variations observed across their homologues. Biochimie, 167, 162–170. doi:10.1016/j.biochi.2019.09.013
    [BibTeX] [Abstract]

    Understanding the structural plasticity of proteins is key to understanding the intricacies of their functions and mechanistic basis. In the current study, we analyzed the available multiple crystal structures of the same protein for the structural differences. For this purpose we used an abstraction of protein structures referred as Protein Blocks (PBs) that was previously established. We also characterized the nature of the structural variations for a few proteins using molecular dynamics simulations. In both the cases, the structural variations were summarized in the form of substitution matrices of PBs. We show that certain conformational states are preferably replaced by other specific conformational states. Interestingly, these structural variations are highly similar to those previously observed across structures of homologous proteins (r2=0.923) or across the ensemble of conformations from NMR data (r2=0.919). Thus our study quantitatively shows that overall trends of structural changes in a given protein are nearly identical to the trends of structural differences that occur in the topologically equivalent positions in homologous proteins. Specific case studies are used to illustrate the nature of these structural variations.

    @article{Vetrivel:2019aa,
    abstract = {Understanding the structural plasticity of proteins is key to understanding the intricacies of their functions and mechanistic basis. In the current study, we analyzed the available multiple crystal structures of the same protein for the structural differences. For this purpose we used an abstraction of protein structures referred as Protein Blocks (PBs) that was previously established. We also characterized the nature of the structural variations for a few proteins using molecular dynamics simulations. In both the cases, the structural variations were summarized in the form of substitution matrices of PBs. We show that certain conformational states are preferably replaced by other specific conformational states. Interestingly, these structural variations are highly similar to those previously observed across structures of homologous proteins (r2=0.923) or across the ensemble of conformations from NMR data (r2=0.919). Thus our study quantitatively shows that overall trends of structural changes in a given protein are nearly identical to the trends of structural differences that occur in the topologically equivalent positions in homologous proteins. Specific case studies are used to illustrate the nature of these structural variations.},
    author = {Vetrivel, Iyanar and de Brevern, Alexandre G and Cadet, Fr{\'e}d{\'e}ric and Srinivasan, Narayanaswamy and Offmann, Bernard},
    date-added = {2019-10-12 00:55:39 +0200},
    date-modified = {2019-10-12 00:55:39 +0200},
    doi = {10.1016/j.biochi.2019.09.013},
    journal = {Biochimie},
    journal-full = {Biochimie},
    keywords = {Molecular dynamics; Protein conformation; Protein structural variation; Structural alphabet},
    month = {December},
    pages = {162--170},
    pmid = {31560932},
    title = {Structural variations within proteins can be as large as variations observed across their homologues},
    volume = {167},
    year = {2019},
    Bdsk-Url-1 = {https://doi.org/10.1016/j.biochi.2019.09.013}}

  • Chaaya, N., Shahsavarian, M. A., Maffucci, I., Friboulet, A., Offmann, B., Léger, J., Rousseau, S., Avalle, B., & Padiolleau-Lefèvre, S.. (2019). Genetic background and immunological status influence b cell repertoire diversity in mice. Sci rep, 9(1), 14261. doi:10.1038/s41598-019-50714-y
    [BibTeX] [Abstract]

    The relationship between the immune repertoire and the physiopathological status of individuals is essential to apprehend the genesis and the evolution of numerous pathologies. Nevertheless, the methodological approaches to understand these complex interactions are challenging. We performed a study evaluating the diversity harbored by different immune repertoires as a function of their physiopathological status. In this study, we base our analysis on a murine scFv library previously described and representing four different immune repertoires: i) healthy and na{\”\i}ve, ii) healthy and immunized, iii) autoimmune prone and na{\”\i}ve, and iv) autoimmune prone and immunized. This library, 2.6 × 109 in size, is submitted to high throughput sequencing (Next Generation Sequencing, NGS) in order to analyze the gene subgroups encoding for immunoglobulins. A comparative study of the distribution of immunoglobulin gene subgroups present in the four libraries has revealed shifts in the B cell repertoire originating from differences in genetic background and immunological status of mice.

    @article{Chaaya:2019aa,
    abstract = {The relationship between the immune repertoire and the physiopathological status of individuals is essential to apprehend the genesis and the evolution of numerous pathologies. Nevertheless, the methodological approaches to understand these complex interactions are challenging. We performed a study evaluating the diversity harbored by different immune repertoires as a function of their physiopathological status. In this study, we base our analysis on a murine scFv library previously described and representing four different immune repertoires: i) healthy and na{\"\i}ve, ii) healthy and immunized, iii) autoimmune prone and na{\"\i}ve, and iv) autoimmune prone and immunized. This library, 2.6 × 109 in size, is submitted to high throughput sequencing (Next Generation Sequencing, NGS) in order to analyze the gene subgroups encoding for immunoglobulins. A comparative study of the distribution of immunoglobulin gene subgroups present in the four libraries has revealed shifts in the B cell repertoire originating from differences in genetic background and immunological status of mice.},
    author = {Chaaya, Nancy and Shahsavarian, Melody A and Maffucci, Irene and Friboulet, Alain and Offmann, Bernard and L{\'e}ger, Jean-Benoist and Rousseau, Sylvain and Avalle, B{\'e}rang{\`e}re and Padiolleau-Lef{\`e}vre, S{\'e}verine},
    date-added = {2019-10-12 00:55:38 +0200},
    date-modified = {2019-10-12 00:55:38 +0200},
    doi = {10.1038/s41598-019-50714-y},
    journal = {Sci Rep},
    journal-full = {Scientific reports},
    month = {Oct},
    number = {1},
    pages = {14261},
    pmid = {31582818},
    pst = {epublish},
    title = {Genetic background and immunological status influence B cell repertoire diversity in mice},
    volume = {9},
    year = {2019},
    Bdsk-Url-1 = {https://doi.org/10.1038/s41598-019-50714-y}}

  • Ghosh, P., Joshi, A., Guita, N., Offmann, B., & Sowdhamini, R.. (2019). Ecrbpome: a comprehensive database of all known e. coli rna-binding proteins. Bmc genomics, 20(1), 403. doi:10.1186/s12864-019-5755-5
    [BibTeX] [Abstract]

    The repertoire of RNA-binding proteins (RBPs) in bacteria play a crucial role in their survival, and interactions with the host machinery, but there is little information, record or characterisation in bacterial genomes. As a first step towards this, we have chosen the bacterial model system Escherichia coli, and organised all RBPs in this organism into a comprehensive database named EcRBPome. It contains RBPs recorded from 614 complete E. coli proteomes available in the RefSeq database (as of October 2018). The database provides various features related to the E. coli RBPs, like their domain architectures, PDB structures, GO and EC annotations etc. It provides the assembly, bioproject and biosample details of each strain, as well as cross-strain comparison of occurrences of various RNA-binding domains (RBDs). The percentage of RBPs, the abundance of the various RBDs harboured by each strain have been graphically represented in this database and available alongside other files for user download. To the best of our knowledge, this is the first database of its kind and we hope that it will be of great use to the biological community.

    @article{Ghosh:2019aa,
    abstract = {The repertoire of RNA-binding proteins (RBPs) in bacteria play a crucial role in their survival, and interactions with the host machinery, but there is little information, record or characterisation in bacterial genomes. As a first step towards this, we have chosen the bacterial model system Escherichia coli, and organised all RBPs in this organism into a comprehensive database named EcRBPome. It contains RBPs recorded from 614 complete E. coli proteomes available in the RefSeq database (as of October 2018). The database provides various features related to the E. coli RBPs, like their domain architectures, PDB structures, GO and EC annotations etc. It provides the assembly, bioproject and biosample details of each strain, as well as cross-strain comparison of occurrences of various RNA-binding domains (RBDs). The percentage of RBPs, the abundance of the various RBDs harboured by each strain have been graphically represented in this database and available alongside other files for user download. To the best of our knowledge, this is the first database of its kind and we hope that it will be of great use to the biological community.},
    author = {Ghosh, Pritha and Joshi, Adwait and Guita, Niang and Offmann, Bernard and Sowdhamini, R},
    date-added = {2019-10-12 00:55:40 +0200},
    date-modified = {2019-10-12 00:55:40 +0200},
    doi = {10.1186/s12864-019-5755-5},
    journal = {BMC Genomics},
    journal-full = {BMC genomics},
    keywords = {Cross-genome comparison; Database; Escherichia coli; Genome-wide survey; Pathotypes; Proteomes; RNA-binding proteins},
    month = {May},
    number = {1},
    pages = {403},
    pmc = {PMC6530084},
    pmid = {31117939},
    pst = {epublish},
    title = {EcRBPome: a comprehensive database of all known E. coli RNA-binding proteins},
    volume = {20},
    year = {2019},
    Bdsk-Url-1 = {https://doi.org/10.1186/s12864-019-5755-5}}

  • Vetrivel, I., Hoffmann, L., Guegan, S., Offmann, B., & Laurent, A.. (2019). Pbmapclust: mapping and clustering the protein conformational space using a structural alphabet. , 1-5.
    [BibTeX]
    @article{vetrivelpbmapclust,
    author = {Vetrivel, I and Hoffmann, L and Guegan, S and Offmann, B and Laurent, AD},
    booktitle = {Workshop on Molecular Graphics and Visual Analysis of Molecular Data},
    date-added = {2020-02-23 21:15:20 +0100},
    date-modified = {2020-02-23 21:15:20 +0100},
    editor = {Byska, J and Krone, M and Sommer B},
    pages = {1-5},
    title = {PBmapclust: Mapping and Clustering the Protein Conformational Space Using a Structural Alphabet},
    year = {2019}}

  • Ajjolli Nagaraja, A., Fontaine, N., Delsaut, M., Charton, P., Damour, C., Offmann, B., Grondin-Perez, B., & Cadet, F.. (2019). Flux prediction using artificial neural network (ann) for the upper part of glycolysis. Plos one, 14(5), e0216178. doi:10.1371/journal.pone.0216178
    [BibTeX] [Abstract]

    The selection of optimal enzyme concentration in multienzyme cascade reactions for the highest product yield in practice is very expensive and time-consuming process. The modelling of biological pathways is a difficult process because of the complexity of the system. The mathematical modelling of the system using an analytical approach depends on the many parameters of enzymes which rely on tedious and expensive experiments. The artificial neural network (ANN) method has been successively applied in different fields of science to perform complex functions. In this study, ANN models were trained to predict the flux for the upper part of glycolysis as inferred by NADH consumption, using four enzyme concentrations i.e., phosphoglucoisomerase, phosphofructokinase, fructose-bisphosphate-aldolase, triose-phosphate-isomerase. Out of three ANN algorithms, the neuralnet package with two activation functions, “logistic” and “tanh” were implemented. The prediction of the flux was very efficient: RMSE and R2 were 0.847, 0.93 and 0.804, 0.94 respectively for logistic and tanh functions using a cross validation procedure. This study showed that a systemic approach such as ANN could be used for accurate prediction of the flux through the metabolic pathway. This could help to save a lot of time and costs, particularly from an industrial perspective. The R-code is available at: https://github.com/DSIMB/ANN-Glycolysis-Flux-Prediction.

    @article{Ajjolli-Nagaraja:2019aa,
    abstract = {The selection of optimal enzyme concentration in multienzyme cascade reactions for the highest product yield in practice is very expensive and time-consuming process. The modelling of biological pathways is a difficult process because of the complexity of the system. The mathematical modelling of the system using an analytical approach depends on the many parameters of enzymes which rely on tedious and expensive experiments. The artificial neural network (ANN) method has been successively applied in different fields of science to perform complex functions. In this study, ANN models were trained to predict the flux for the upper part of glycolysis as inferred by NADH consumption, using four enzyme concentrations i.e., phosphoglucoisomerase, phosphofructokinase, fructose-bisphosphate-aldolase, triose-phosphate-isomerase. Out of three ANN algorithms, the neuralnet package with two activation functions, "logistic" and "tanh" were implemented. The prediction of the flux was very efficient: RMSE and R2 were 0.847, 0.93 and 0.804, 0.94 respectively for logistic and tanh functions using a cross validation procedure. This study showed that a systemic approach such as ANN could be used for accurate prediction of the flux through the metabolic pathway. This could help to save a lot of time and costs, particularly from an industrial perspective. The R-code is available at: https://github.com/DSIMB/ANN-Glycolysis-Flux-Prediction.},
    author = {Ajjolli Nagaraja, Anamya and Fontaine, Nicolas and Delsaut, Mathieu and Charton, Philippe and Damour, Cedric and Offmann, Bernard and Grondin-Perez, Brigitte and Cadet, Frederic},
    date-added = {2019-10-12 00:55:41 +0200},
    date-modified = {2019-10-12 00:55:41 +0200},
    doi = {10.1371/journal.pone.0216178},
    journal = {PLoS One},
    journal-full = {PloS one},
    number = {5},
    pages = {e0216178},
    pmc = {PMC6505829},
    pmid = {31067238},
    pst = {epublish},
    title = {Flux prediction using artificial neural network (ANN) for the upper part of glycolysis},
    volume = {14},
    year = {2019},
    Bdsk-Url-1 = {https://doi.org/10.1371/journal.pone.0216178}}

  • Liu, G., Arnaud, P., Offmann, B., & Picimbon, J.. (2019). Pheromone, natural odor and odorant reception suppressing agent (orsa) for insect control. In Olfactory concepts of insect control-alternative to insecticides (pp. 311–345). Springer, cham.
    [BibTeX] [Abstract]

    Odorant-binding proteins (OBPs) are small “bowl-like” globular pro- teins, highly abundant in the antennae of most insect species. These proteins are believed to mediate reception of odor molecules at the periphery of sensory receptor neurons. Therefore, they may represent crucial targets for becoming new methods of insect pest control by directly interfering with the olfactory acuity of the insect. The current better understanding of molecular mechanisms underlying odor detec- tion and the knowledge about the functional binding sites of OBPs and many other families of binding proteins in various insect species is elucidated here. Such infor- mation forms the basis for the synthesis of new inhibitor olfactory compounds (Odorant Reception-Suppressing Agents, ORSAs) to interact specifically with the groups of insect pests.

    @incollection{liu2019pheromone,
    abstract = {Odorant-binding proteins (OBPs) are small ``bowl-like'' globular pro- teins, highly abundant in the antennae of most insect species. These proteins are believed to mediate reception of odor molecules at the periphery of sensory receptor neurons. Therefore, they may represent crucial targets for becoming new methods of insect pest control by directly interfering with the olfactory acuity of the insect. The current better understanding of molecular mechanisms underlying odor detec- tion and the knowledge about the functional binding sites of OBPs and many other families of binding proteins in various insect species is elucidated here. Such infor- mation forms the basis for the synthesis of new inhibitor olfactory compounds (Odorant Reception-Suppressing Agents, ORSAs) to interact specifically with the groups of insect pests.},
    author = {Liu, Guoxia and Arnaud, Philippe and Offmann, Bernard and Picimbon, Jean-Fran{\c{c}}ois},
    booktitle = {Olfactory Concepts of Insect Control-Alternative to Insecticides},
    pages = {311--345},
    publisher = {Springer, Cham},
    title = {Pheromone, Natural Odor and Odorant Reception Suppressing Agent (ORSA) for Insect Control},
    year = {2019},
    Bdsk-File-1 = {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},
    Bdsk-Url-1 = {https://doi.org/10.1007/978-3-030-05165-5}}

2018

  • Cadet, F., Fontaine, N., Li, G., Sanchis, J., Ng Fuk Chong, M., Pandjaitan, R., Vetrivel, I., Offmann, B., & Reetz, M. T.. (2018). A machine learning approach for reliable prediction of amino acid interactions and its application in the directed evolution of enantioselective enzymes. Sci rep, 8(1), 16757. doi:10.1038/s41598-018-35033-y
    [BibTeX] [Abstract]

    Directed evolution is an important research activity in synthetic biology and biotechnology. Numerous reports describe the application of tedious mutation/screening cycles for the improvement of proteins. Recently, knowledge-based approaches have facilitated the prediction of protein properties and the identification of improved mutants. However, epistatic phenomena constitute an obstacle which can impair the predictions in protein engineering. We present an innovative sequence-activity relationship (innov’SAR) methodology based on digital signal processing combining wet-lab experimentation and computational protein design. In our machine learning approach, a predictive model is developed to find the resulting property of the protein when the n single point mutations are permuted (2n combinations). The originality of our approach is that only sequence information and the fitness of mutants measured in the wet-lab are needed to build models. We illustrate the application of the approach in the case of improving the enantioselectivity of an epoxide hydrolase from Aspergillus niger. n = 9 single point mutants of the enzyme were experimentally assessed for their enantioselectivity and used as a learning dataset to build a model. Based on combinations of the 9 single point mutations (29), the enantioselectivity of these 512 variants were predicted, and candidates were experimentally checked: better mutants with higher enantioselectivity were indeed found.

    @article{Cadet:2018aa,
    abstract = {Directed evolution is an important research activity in synthetic biology and biotechnology. Numerous reports describe the application of tedious mutation/screening cycles for the improvement of proteins. Recently, knowledge-based approaches have facilitated the prediction of protein properties and the identification of improved mutants. However, epistatic phenomena constitute an obstacle which can impair the predictions in protein engineering. We present an innovative sequence-activity relationship (innov'SAR) methodology based on digital signal processing combining wet-lab experimentation and computational protein design. In our machine learning approach, a predictive model is developed to find the resulting property of the protein when the n single point mutations are permuted (2n combinations). The originality of our approach is that only sequence information and the fitness of mutants measured in the wet-lab are needed to build models. We illustrate the application of the approach in the case of improving the enantioselectivity of an epoxide hydrolase from Aspergillus niger. n = 9 single point mutants of the enzyme were experimentally assessed for their enantioselectivity and used as a learning dataset to build a model. Based on combinations of the 9 single point mutations (29), the enantioselectivity of these 512 variants were predicted, and candidates were experimentally checked: better mutants with higher enantioselectivity were indeed found.},
    author = {Cadet, Fr{\'e}d{\'e}ric and Fontaine, Nicolas and Li, Guangyue and Sanchis, Joaquin and Ng Fuk Chong, Matthieu and Pandjaitan, Rudy and Vetrivel, Iyanar and Offmann, Bernard and Reetz, Manfred T},
    date-added = {2019-10-12 00:55:42 +0200},
    date-modified = {2019-10-12 00:55:42 +0200},
    doi = {10.1038/s41598-018-35033-y},
    journal = {Sci Rep},
    journal-full = {Scientific reports},
    month = {11},
    number = {1},
    pages = {16757},
    pmc = {PMC6233173},
    pmid = {30425279},
    pst = {epublish},
    title = {A machine learning approach for reliable prediction of amino acid interactions and its application in the directed evolution of enantioselective enzymes},
    volume = {8},
    year = {2018},
    Bdsk-Url-1 = {https://doi.org/10.1038/s41598-018-35033-y}}

2017

  • Liu, G., Arnaud, P., Offmann, B., & Picimbon, J.. (2017). Genotyping and bio-sensing chemosensory proteins in insects. Sensors (basel), 17(8). doi:10.3390/s17081801
    [BibTeX] [Abstract]

    Genotyping is the process of determining differences in the genetic make-up of an individual and comparing it to that of another individual. Focus on the family of chemosensory proteins (CSPs) in insects reveals differences at the genomic level across various strains and biotypes, but none at the level of individuals, which could be extremely useful in the biotyping of insect pest species necessary for the agricultural, medical and veterinary industries. Proposed methods of genotyping CSPs include not only restriction enzymatic cleavage and amplification of cleaved polymorphic sequences, but also detection of retroposons in some specific regions of the insect chromosome. Design of biosensors using CSPs addresses tissue-specific RNA mutations in a particular subtype of the protein, which could be used as a marker of specific physiological conditions. Additionally, we refer to the binding properties of CSP proteins tuned to lipids and xenobiotic insecticides for the development of a new generation of biosensor chips, monitoring lipid blood concentration and chemical environmental pollution.

    @article{Liu:2017aa,
    abstract = {Genotyping is the process of determining differences in the genetic make-up of an individual and comparing it to that of another individual. Focus on the family of chemosensory proteins (CSPs) in insects reveals differences at the genomic level across various strains and biotypes, but none at the level of individuals, which could be extremely useful in the biotyping of insect pest species necessary for the agricultural, medical and veterinary industries. Proposed methods of genotyping CSPs include not only restriction enzymatic cleavage and amplification of cleaved polymorphic sequences, but also detection of retroposons in some specific regions of the insect chromosome. Design of biosensors using CSPs addresses tissue-specific RNA mutations in a particular subtype of the protein, which could be used as a marker of specific physiological conditions. Additionally, we refer to the binding properties of CSP proteins tuned to lipids and xenobiotic insecticides for the development of a new generation of biosensor chips, monitoring lipid blood concentration and chemical environmental pollution.},
    author = {Liu, Guoxia and Arnaud, Philippe and Offmann, Bernard and Picimbon, Jean-Fran{\c c}ois},
    date-added = {2019-10-12 00:55:43 +0200},
    date-modified = {2019-10-12 00:55:43 +0200},
    doi = {10.3390/s17081801},
    journal = {Sensors (Basel)},
    journal-full = {Sensors (Basel, Switzerland)},
    keywords = {RNA editing; biotype imprinting; genosensing; lipometer; mutation sensor},
    mesh = {Animals; Genotype; Insect Proteins; Insecta; Phylogeny; Receptors, Odorant},
    month = {Aug},
    number = {8},
    pmc = {PMC5579523},
    pmid = {28777348},
    pst = {epublish},
    title = {Genotyping and Bio-Sensing Chemosensory Proteins in Insects},
    volume = {17},
    year = {2017},
    Bdsk-Url-1 = {https://doi.org/10.3390/s17081801}}

  • Labbé, P., Faure, E., Lecointe, S., Le Scouarnec, S., Kyndt, F., Marrec, M., Le Tourneau, T., Offmann, B., Duplaà, C., Zaffran, S., Schott, J. J., & Merot, J.. (2017). The alternatively spliced lrrfip1 isoform-1 is a key regulator of the wnt/β-catenin transcription pathway. Biochim biophys acta mol cell res, 1864(7), 1142-1152. doi:10.1016/j.bbamcr.2017.03.008
    [BibTeX] [Abstract]

    The GC-rich Binding Factor 2/Leucine Rich Repeat in the Flightless 1 Interaction Protein 1 gene (GCF2/LRRFIP1) is predicted to be alternatively spliced in five different isoforms. Although important peptide sequence differences are expected to result from this alternative splicing, to date, only the gene transcription regulator properties of LRRFIP1-Iso5 were unveiled. Based on molecular, cellular and biochemical data, we show here that the five isoforms define two molecular entities with different expression profiles in human tissues, subcellular localizations, oligomerization properties and transcription enhancer properties of the canonical Wnt pathway. We demonstrated that LRRFIP1-Iso3, -4 and -5, which share over 80% sequence identity, are primarily located in the cell cytoplasm and form homo and hetero-multimers between each other. In contrast, LRRFIP1-Iso1 and -2 are primarily located in the cell nucleus in part thanks to their shared C-terminal domain. Furthermore, we showed that LRRFIP1-Iso1 is preferentially expressed in the myocardium and skeletal muscle. Using the in vitro Topflash reporter assay we revealed that among LRRFIP1 isoforms, LRRFIP1-Iso1 is the strongest enhancer of the β-catenin Wnt canonical transcription pathway thanks to a specific N-terminal domain harboring two critical tryptophan residues (W76, 82). In addition, we showed that the Wnt enhancer properties of LRRFIP1-Iso1 depend on its homo-dimerisation which is governed by its specific coiled coil domain. Together our study identified LRRFIP1-Iso1 as a critical regulator of the Wnt canonical pathway with a potential role in myocyte differentiation and myogenesis.

    @article{Labbe:2017aa,
    abstract = {The GC-rich Binding Factor 2/Leucine Rich Repeat in the Flightless 1 Interaction Protein 1 gene (GCF2/LRRFIP1) is predicted to be alternatively spliced in five different isoforms. Although important peptide sequence differences are expected to result from this alternative splicing, to date, only the gene transcription regulator properties of LRRFIP1-Iso5 were unveiled. Based on molecular, cellular and biochemical data, we show here that the five isoforms define two molecular entities with different expression profiles in human tissues, subcellular localizations, oligomerization properties and transcription enhancer properties of the canonical Wnt pathway. We demonstrated that LRRFIP1-Iso3, -4 and -5, which share over 80% sequence identity, are primarily located in the cell cytoplasm and form homo and hetero-multimers between each other. In contrast, LRRFIP1-Iso1 and -2 are primarily located in the cell nucleus in part thanks to their shared C-terminal domain. Furthermore, we showed that LRRFIP1-Iso1 is preferentially expressed in the myocardium and skeletal muscle. Using the in vitro Topflash reporter assay we revealed that among LRRFIP1 isoforms, LRRFIP1-Iso1 is the strongest enhancer of the β-catenin Wnt canonical transcription pathway thanks to a specific N-terminal domain harboring two critical tryptophan residues (W76, 82). In addition, we showed that the Wnt enhancer properties of LRRFIP1-Iso1 depend on its homo-dimerisation which is governed by its specific coiled coil domain. Together our study identified LRRFIP1-Iso1 as a critical regulator of the Wnt canonical pathway with a potential role in myocyte differentiation and myogenesis.},
    author = {Labb{\'e}, Pauline and Faure, Emilie and Lecointe, Simon and Le Scouarnec, Solena and Kyndt, Florence and Marrec, Marie and Le Tourneau, Thierry and Offmann, Bernard and Dupla{\`a}, C{\'e}cile and Zaffran, St{\'e}phane and Schott, Jean Jacques and Merot, Jean},
    date-added = {2019-10-12 00:55:44 +0200},
    date-modified = {2019-10-12 00:55:44 +0200},
    doi = {10.1016/j.bbamcr.2017.03.008},
    journal = {Biochim Biophys Acta Mol Cell Res},
    journal-full = {Biochimica et biophysica acta. Molecular cell research},
    keywords = {Coiled coil domain; LEF-TCF; Leucine rich repeat; Muscle differentiation; Wnt catenin transcription},
    mesh = {Alternative Splicing; Animals; Cells, Cultured; HEK293 Cells; Humans; Male; Mice; Muscle, Skeletal; Myocardium; Protein Domains; Protein Isoforms; RNA-Binding Proteins; Rats; Rats, Sprague-Dawley; Wnt Proteins; Wnt Signaling Pathway; beta Catenin},
    month = {Jul},
    number = {7},
    pages = {1142-1152},
    pmid = {28322931},
    pst = {ppublish},
    title = {The alternatively spliced LRRFIP1 Isoform-1 is a key regulator of the Wnt/β-catenin transcription pathway},
    volume = {1864},
    year = {2017},
    Bdsk-Url-1 = {https://doi.org/10.1016/j.bbamcr.2017.03.008}}

  • Shahsavarian, M. A., Chaaya, N., Costa, N., Boquet, D., Atkinson, A., Offmann, B., Kaveri, S. V., Lacroix-Desmazes, S., Friboulet, A., Avalle, B., & Padiolleau-Lefèvre, S.. (2017). Multitarget selection of catalytic antibodies with β-lactamase activity using phage display. Febs j, 284(4), 634-653. doi:10.1111/febs.14012
    [BibTeX] [Abstract]

    β-lactamase enzymes responsible for bacterial resistance to antibiotics are among the most important health threats to the human population today. Understanding the increasingly vast structural motifs responsible for the catalytic mechanism of β-lactamases will help improve the future design of new generation antibiotics and mechanism-based inhibitors of these enzymes. Here we report the construction of a large murine single chain fragment variable (scFv) phage display library of size 2.7 × 109 with extended diversity by combining different mouse models. We have used two molecularly different inhibitors of the R-TEM β-lactamase as targets for selection of catalytic antibodies with β-lactamase activity. This novel methodology has led to the isolation of five antibody fragments, which are all capable of hydrolyzing the β-lactam ring. Structural modeling of the selected scFv has revealed the presence of different motifs in each of the antibody fragments potentially responsible for their catalytic activity. Our results confirm (a) the validity of using our two target inhibitors for the in vitro selection of catalytic antibodies endowed with β-lactamase activity, and (b) the plasticity of the β-lactamase active site responsible for the wide resistance of these enzymes to clinically available inhibitors and antibiotics.

    @article{Shahsavarian:2017aa,
    abstract = {β-lactamase enzymes responsible for bacterial resistance to antibiotics are among the most important health threats to the human population today. Understanding the increasingly vast structural motifs responsible for the catalytic mechanism of β-lactamases will help improve the future design of new generation antibiotics and mechanism-based inhibitors of these enzymes. Here we report the construction of a large murine single chain fragment variable (scFv) phage display library of size 2.7 × 109 with extended diversity by combining different mouse models. We have used two molecularly different inhibitors of the R-TEM β-lactamase as targets for selection of catalytic antibodies with β-lactamase activity. This novel methodology has led to the isolation of five antibody fragments, which are all capable of hydrolyzing the β-lactam ring. Structural modeling of the selected scFv has revealed the presence of different motifs in each of the antibody fragments potentially responsible for their catalytic activity. Our results confirm (a) the validity of using our two target inhibitors for the in vitro selection of catalytic antibodies endowed with β-lactamase activity, and (b) the plasticity of the β-lactamase active site responsible for the wide resistance of these enzymes to clinically available inhibitors and antibiotics.},
    author = {Shahsavarian, Melody A and Chaaya, Nancy and Costa, Narciso and Boquet, Didier and Atkinson, Alexandre and Offmann, Bernard and Kaveri, Srini V and Lacroix-Desmazes, S{\'e}bastien and Friboulet, Alain and Avalle, B{\'e}rang{\`e}re and Padiolleau-Lef{\`e}vre, S{\'e}verine},
    date-added = {2019-10-12 00:55:45 +0200},
    date-modified = {2019-10-12 00:55:45 +0200},
    doi = {10.1111/febs.14012},
    journal = {FEBS J},
    journal-full = {The FEBS journal},
    keywords = {catalytic antibody; enzyme inhibitor; phage display; scFv library; β-lactamase},
    mesh = {Amino Acid Sequence; Animals; Antibodies, Catalytic; Catalytic Domain; Cloning, Molecular; Escherichia coli; Gene Expression; Hydrolysis; Immunization; Kinetics; Mice; Models, Molecular; Penicillins; Peptide Library; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Secondary; Recombinant Proteins; Sequence Alignment; Single-Chain Antibodies; Structure-Activity Relationship; Substrate Specificity; beta-Lactamases; beta-Lactams},
    month = {02},
    number = {4},
    pages = {634-653},
    pmid = {28075071},
    pst = {ppublish},
    title = {Multitarget selection of catalytic antibodies with β-lactamase activity using phage display},
    volume = {284},
    year = {2017},
    Bdsk-Url-1 = {https://doi.org/10.1111/febs.14012}}

  • Vetrivel, I., Mahajan, S., Tyagi, M., Hoffmann, L., Sanejouand, Y., Srinivasan, N., de Brevern, A. G., Cadet, F., & Offmann, B.. (2017). Knowledge-based prediction of protein backbone conformation using a structural alphabet. Plos one, 12(11), e0186215. doi:10.1371/journal.pone.0186215
    [BibTeX] [Abstract]

    Libraries of structural prototypes that abstract protein local structures are known as structural alphabets and have proven to be very useful in various aspects of protein structure analyses and predictions. One such library, Protein Blocks, is composed of 16 standard 5-residues long structural prototypes. This form of analyzing proteins involves drafting its structure as a string of Protein Blocks. Predicting the local structure of a protein in terms of protein blocks is the general objective of this work. A new approach, PB-kPRED is proposed towards this aim. It involves (i) organizing the structural knowledge in the form of a database of pentapeptide fragments extracted from all protein structures in the PDB and (ii) applying a knowledge-based algorithm that does not rely on any secondary structure predictions and/or sequence alignment profiles, to scan this database and predict most probable backbone conformations for the protein local structures. Though PB-kPRED uses the structural information from homologues in preference, if available. The predictions were evaluated rigorously on 15,544 query proteins representing a non-redundant subset of the PDB filtered at 30% sequence identity cut-off. We have shown that the kPRED method was able to achieve mean accuracies ranging from 40.8% to 66.3% depending on the availability of homologues. The impact of the different strategies for scanning the database on the prediction was evaluated and is discussed. Our results highlight the usefulness of the method in the context of proteins without any known structural homologues. A scoring function that gives a good estimate of the accuracy of prediction was further developed. This score estimates very well the accuracy of the algorithm (R2 of 0.82). An online version of the tool is provided freely for non-commercial usage at http://www.bo-protscience.fr/kpred/.

    @article{Vetrivel:2017aa,
    abstract = {Libraries of structural prototypes that abstract protein local structures are known as structural alphabets and have proven to be very useful in various aspects of protein structure analyses and predictions. One such library, Protein Blocks, is composed of 16 standard 5-residues long structural prototypes. This form of analyzing proteins involves drafting its structure as a string of Protein Blocks. Predicting the local structure of a protein in terms of protein blocks is the general objective of this work. A new approach, PB-kPRED is proposed towards this aim. It involves (i) organizing the structural knowledge in the form of a database of pentapeptide fragments extracted from all protein structures in the PDB and (ii) applying a knowledge-based algorithm that does not rely on any secondary structure predictions and/or sequence alignment profiles, to scan this database and predict most probable backbone conformations for the protein local structures. Though PB-kPRED uses the structural information from homologues in preference, if available. The predictions were evaluated rigorously on 15,544 query proteins representing a non-redundant subset of the PDB filtered at 30% sequence identity cut-off. We have shown that the kPRED method was able to achieve mean accuracies ranging from 40.8% to 66.3% depending on the availability of homologues. The impact of the different strategies for scanning the database on the prediction was evaluated and is discussed. Our results highlight the usefulness of the method in the context of proteins without any known structural homologues. A scoring function that gives a good estimate of the accuracy of prediction was further developed. This score estimates very well the accuracy of the algorithm (R2 of 0.82). An online version of the tool is provided freely for non-commercial usage at http://www.bo-protscience.fr/kpred/.},
    author = {Vetrivel, Iyanar and Mahajan, Swapnil and Tyagi, Manoj and Hoffmann, Lionel and Sanejouand, Yves-Henri and Srinivasan, Narayanaswamy and de Brevern, Alexandre G and Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard},
    date-added = {2019-10-12 00:55:43 +0200},
    date-modified = {2019-10-12 00:55:43 +0200},
    doi = {10.1371/journal.pone.0186215},
    journal = {PLoS One},
    journal-full = {PloS one},
    mesh = {Algorithms; Amino Acid Sequence; Databases, Protein; Protein Conformation; Protein Folding; Protein Structure, Secondary; Proteins; Proteomics; Sequence Analysis, Protein},
    number = {11},
    pages = {e0186215},
    pmc = {PMC5697859},
    pmid = {29161266},
    pst = {epublish},
    title = {Knowledge-based prediction of protein backbone conformation using a structural alphabet},
    volume = {12},
    year = {2017},
    Bdsk-Url-1 = {https://doi.org/10.1371/journal.pone.0186215}}

2016

  • Verhaeghe, T., De Winter, K., Berland, M., De Vreese, R., D’hooghe, M., Offmann, B., & Desmet, T.. (2016). Converting bulk sugars into prebiotics: semi-rational design of a transglucosylase with controlled selectivity. Chem commun (camb), 52(18), 3687-9. doi:10.1039/c5cc09940d
    [BibTeX] [Abstract]

    Despite the growing importance of prebiotics in nutrition and gastroenterology, their structural variety is currently still very limited. The lack of straightforward procedures to gain new products in sufficient amounts often hampers application testing and further development. Although the enzyme sucrose phosphorylase can be used to produce the rare disaccharide kojibiose (α-1,2-glucobiose) from the bulk sugars sucrose and glucose, the target compound is only a side product that is difficult to isolate. Accordingly, for this biocatalyst to become economically attractive, the formation of other glucobioses should be avoided and therefore we applied semi-rational mutagenesis and low-throughput screening, which resulted in a double mutant (L341I_Q345S) with a selectivity of 95% for kojibiose. That way, an efficient and scalable production process with a yield of 74% could be established, and with a simple yeast treatment and crystallization step over a hundred grams of highly pure kojibiose (>99.5%) was obtained.

    @article{Verhaeghe:2016aa,
    abstract = {Despite the growing importance of prebiotics in nutrition and gastroenterology, their structural variety is currently still very limited. The lack of straightforward procedures to gain new products in sufficient amounts often hampers application testing and further development. Although the enzyme sucrose phosphorylase can be used to produce the rare disaccharide kojibiose (α-1,2-glucobiose) from the bulk sugars sucrose and glucose, the target compound is only a side product that is difficult to isolate. Accordingly, for this biocatalyst to become economically attractive, the formation of other glucobioses should be avoided and therefore we applied semi-rational mutagenesis and low-throughput screening, which resulted in a double mutant (L341I_Q345S) with a selectivity of 95% for kojibiose. That way, an efficient and scalable production process with a yield of 74% could be established, and with a simple yeast treatment and crystallization step over a hundred grams of highly pure kojibiose (>99.5%) was obtained. },
    author = {Verhaeghe, Tom and De Winter, Karel and Berland, Magali and De Vreese, Rob and D'hooghe, Matthias and Offmann, Bernard and Desmet, Tom},
    date-added = {2019-10-12 00:55:47 +0200},
    date-modified = {2019-10-12 00:55:47 +0200},
    doi = {10.1039/c5cc09940d},
    journal = {Chem Commun (Camb)},
    journal-full = {Chemical communications (Cambridge, England)},
    mesh = {Carbohydrates; Disaccharides; Glucosyltransferases; Molecular Structure; Prebiotics},
    month = {Mar},
    number = {18},
    pages = {3687-9},
    pmid = {26858011},
    pst = {ppublish},
    title = {Converting bulk sugars into prebiotics: semi-rational design of a transglucosylase with controlled selectivity},
    volume = {52},
    year = {2016},
    Bdsk-Url-1 = {https://doi.org/10.1039/c5cc09940d}}

  • Liu, G., Ma, H., Xie, H., Xuan, N., Guo, X., Fan, Z., Rajashekar, B., Arnaud, P., Offmann, B., & Picimbon, J.. (2016). Biotype characterization, developmental profiling, insecticide response and binding property of bemisia tabaci chemosensory proteins: role of csp in insect defense. Plos one, 11(5), e0154706. doi:10.1371/journal.pone.0154706
    [BibTeX] [Abstract]

    Chemosensory proteins (CSPs) are believed to play a key role in the chemosensory process in insects. Sequencing genomic DNA and RNA encoding CSP1, CSP2 and CSP3 in the sweet potato whitefly Bemisia tabaci showed strong variation between B and Q biotypes. Analyzing CSP-RNA levels showed not only biotype, but also age and developmental stage-specific expression. Interestingly, applying neonicotinoid thiamethoxam insecticide using twenty-five different dose/time treatments in B and Q young adults showed that Bemisia CSP1, CSP2 and CSP3 were also differentially regulated over insecticide exposure. In our study one of the adult-specific gene (CSP1) was shown to be significantly up-regulated by the insecticide in Q, the most highly resistant form of B. tabaci. Correlatively, competitive binding assays using tryptophan fluorescence spectroscopy and molecular docking demonstrated that CSP1 protein preferentially bound to linoleic acid, while CSP2 and CSP3 proteins rather associated to another completely different type of chemical, i.e. α-pentyl-cinnamaldehyde (jasminaldehyde). This might indicate that some CSPs in whiteflies are crucial to facilitate the transport of fatty acids thus regulating some metabolic pathways of the insect immune response, while some others are tuned to much more volatile chemicals known not only for their pleasant odor scent, but also for their potent toxic insecticide activity.

    @article{Liu:2016aa,
    abstract = {Chemosensory proteins (CSPs) are believed to play a key role in the chemosensory process in insects. Sequencing genomic DNA and RNA encoding CSP1, CSP2 and CSP3 in the sweet potato whitefly Bemisia tabaci showed strong variation between B and Q biotypes. Analyzing CSP-RNA levels showed not only biotype, but also age and developmental stage-specific expression. Interestingly, applying neonicotinoid thiamethoxam insecticide using twenty-five different dose/time treatments in B and Q young adults showed that Bemisia CSP1, CSP2 and CSP3 were also differentially regulated over insecticide exposure. In our study one of the adult-specific gene (CSP1) was shown to be significantly up-regulated by the insecticide in Q, the most highly resistant form of B. tabaci. Correlatively, competitive binding assays using tryptophan fluorescence spectroscopy and molecular docking demonstrated that CSP1 protein preferentially bound to linoleic acid, while CSP2 and CSP3 proteins rather associated to another completely different type of chemical, i.e. α-pentyl-cinnamaldehyde (jasminaldehyde). This might indicate that some CSPs in whiteflies are crucial to facilitate the transport of fatty acids thus regulating some metabolic pathways of the insect immune response, while some others are tuned to much more volatile chemicals known not only for their pleasant odor scent, but also for their potent toxic insecticide activity.},
    author = {Liu, Guoxia and Ma, Hongmei and Xie, Hongyan and Xuan, Ning and Guo, Xia and Fan, Zhongxue and Rajashekar, Balaji and Arnaud, Philippe and Offmann, Bernard and Picimbon, Jean-Fran{\c c}ois},
    date-added = {2019-10-12 00:55:46 +0200},
    date-modified = {2019-10-12 00:55:46 +0200},
    doi = {10.1371/journal.pone.0154706},
    journal = {PLoS One},
    journal-full = {PloS one},
    mesh = {Acrolein; Amino Acid Sequence; Animals; Clone Cells; Expressed Sequence Tags; Fluorescence; Gene Expression Profiling; Gene Expression Regulation, Developmental; Hemiptera; Insect Proteins; Insecticides; Ligands; Linoleic Acid; Molecular Docking Simulation; Neonicotinoids; Nitro Compounds; Oxazines; Phylogeny; Thiamethoxam; Thiazoles; Time Factors},
    number = {5},
    pages = {e0154706},
    pmc = {PMC4864240},
    pmid = {27167733},
    pst = {epublish},
    title = {Biotype Characterization, Developmental Profiling, Insecticide Response and Binding Property of Bemisia tabaci Chemosensory Proteins: Role of CSP in Insect Defense},
    volume = {11},
    year = {2016},
    Bdsk-Url-1 = {https://doi.org/10.1371/journal.pone.0154706}}

2015

  • Mahajan, S., de Brevern, A. G., Sanejouand, Y., Srinivasan, N., & Offmann, B.. (2015). Use of a structural alphabet to find compatible folds for amino acid sequences. Protein sci, 24(1), 145-53. doi:10.1002/pro.2581
    [BibTeX] [Abstract]

    The structural annotation of proteins with no detectable homologs of known 3D structure identified using sequence-search methods is a major challenge today. We propose an original method that computes the conditional probabilities for the amino-acid sequence of a protein to fit to known protein 3D structures using a structural alphabet, known as “Protein Blocks” (PBs). PBs constitute a library of 16 local structural prototypes that approximate every part of protein backbone structures. It is used to encode 3D protein structures into 1D PB sequences and to capture sequence to structure relationships. Our method relies on amino acid occurrence matrices, one for each PB, to score global and local threading of query amino acid sequences to protein folds encoded into PB sequences. It does not use any information from residue contacts or sequence-search methods or explicit incorporation of hydrophobic effect. The performance of the method was assessed with independent test datasets derived from SCOP 1.75A. With a Z-score cutoff that achieved 95% specificity (i.e., less than 5% false positives), global and local threading showed sensitivity of 64.1% and 34.2%, respectively. We further tested its performance on 57 difficult CASP10 targets that had no known homologs in PDB: 38 compatible templates were identified by our approach and 66% of these hits yielded correctly predicted structures. This method scales-up well and offers promising perspectives for structural annotations at genomic level. It has been implemented in the form of a web-server that is freely available at http://www.bo-protscience.fr/forsa.

    @article{Mahajan:2015aa,
    abstract = {The structural annotation of proteins with no detectable homologs of known 3D structure identified using sequence-search methods is a major challenge today. We propose an original method that computes the conditional probabilities for the amino-acid sequence of a protein to fit to known protein 3D structures using a structural alphabet, known as "Protein Blocks" (PBs). PBs constitute a library of 16 local structural prototypes that approximate every part of protein backbone structures. It is used to encode 3D protein structures into 1D PB sequences and to capture sequence to structure relationships. Our method relies on amino acid occurrence matrices, one for each PB, to score global and local threading of query amino acid sequences to protein folds encoded into PB sequences. It does not use any information from residue contacts or sequence-search methods or explicit incorporation of hydrophobic effect. The performance of the method was assessed with independent test datasets derived from SCOP 1.75A. With a Z-score cutoff that achieved 95% specificity (i.e., less than 5% false positives), global and local threading showed sensitivity of 64.1% and 34.2%, respectively. We further tested its performance on 57 difficult CASP10 targets that had no known homologs in PDB: 38 compatible templates were identified by our approach and 66% of these hits yielded correctly predicted structures. This method scales-up well and offers promising perspectives for structural annotations at genomic level. It has been implemented in the form of a web-server that is freely available at http://www.bo-protscience.fr/forsa.},
    author = {Mahajan, Swapnil and de Brevern, Alexandre G and Sanejouand, Yves-Henri and Srinivasan, Narayanaswamy and Offmann, Bernard},
    date-added = {2019-10-12 00:55:47 +0200},
    date-modified = {2019-10-12 00:55:47 +0200},
    doi = {10.1002/pro.2581},
    journal = {Protein Sci},
    journal-full = {Protein science : a publication of the Protein Society},
    keywords = {fold recognition; protein blocks; protein domains; protein structures; sequence-structure relationship; structural alphabet; structural annotation; threading},
    mesh = {Algorithms; Amino Acid Sequence; Models, Molecular; Molecular Sequence Data; Protein Conformation; Protein Folding; Proteins; Sequence Alignment; Sequence Analysis, Protein},
    month = {Jan},
    number = {1},
    pages = {145-53},
    pmc = {PMC4282420},
    pmid = {25297700},
    pst = {ppublish},
    title = {Use of a structural alphabet to find compatible folds for amino acid sequences},
    volume = {24},
    year = {2015},
    Bdsk-Url-1 = {https://doi.org/10.1002/pro.2581}}

  • Fontaine, N., Grondin-Perez, B., Cadet, F., & Offmann, B.. (2015). Modeling of a cell-free synthetic system for biohydrogen production. Journal of computer science & systems biology, 8(3), 132–139.
    [BibTeX]
    @article{fontaine2015modeling,
    author = {Fontaine, Nicolas and Grondin-Perez, Brigitte and Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard},
    journal = {Journal of Computer Science \& Systems Biology},
    number = {3},
    pages = {132--139},
    title = {Modeling of a Cell-Free Synthetic System for Biohydrogen Production},
    volume = {8},
    year = {2015}}

2014

  • Berland, M., Offmann, B., André, I., Remaud-Siméon, M., & Charton, P.. (2014). A web-based tool for rational screening of mutants libraries using prosar. Protein eng des sel, 27(10), 375-81. doi:10.1093/protein/gzu035
    [BibTeX] [Abstract]

    In directed evolution experiments, it is at stake to have methods to screen efficiently the mutant libraries. We propose a web-based tool that implements an established in silico method for the rational screening of mutant libraries. The method, known as ProSAR, attempts to link sequence data to activity. The method uses statistical models trained on small experimental datasets provided by the user. These can integrate potential epistatic interactions between mutations and be used in many diverse biological contexts. It drastically improves the search for leading mutants. The tool is freely available to non-commercial users at http://bo-protscience.fr/prosar/.

    @article{Berland:2014aa,
    abstract = {In directed evolution experiments, it is at stake to have methods to screen efficiently the mutant libraries. We propose a web-based tool that implements an established in silico method for the rational screening of mutant libraries. The method, known as ProSAR, attempts to link sequence data to activity. The method uses statistical models trained on small experimental datasets provided by the user. These can integrate potential epistatic interactions between mutations and be used in many diverse biological contexts. It drastically improves the search for leading mutants. The tool is freely available to non-commercial users at http://bo-protscience.fr/prosar/. },
    author = {Berland, Magali and Offmann, Bernard and Andr{\'e}, Isabelle and Remaud-Sim{\'e}on, Magali and Charton, Philippe},
    date-added = {2019-10-12 00:55:48 +0200},
    date-modified = {2019-10-12 00:55:48 +0200},
    doi = {10.1093/protein/gzu035},
    journal = {Protein Eng Des Sel},
    journal-full = {Protein engineering, design \& selection : PEDS},
    keywords = {epistatic interactions between mutations; fitness landscape exploration; protein engineering; rational screening; sequence--activity relationship},
    mesh = {Algorithms; Databases, Protein; Directed Molecular Evolution; Gene Library; Internet; Mutation; Proteomics; Regression Analysis; Software},
    month = {Oct},
    number = {10},
    pages = {375-81},
    pmid = {25169579},
    pst = {ppublish},
    title = {A web-based tool for rational screening of mutants libraries using ProSAR},
    volume = {27},
    year = {2014},
    Bdsk-Url-1 = {https://doi.org/10.1093/protein/gzu035}}

  • Mahajan, S., de Brevern, A. G., Offmann, B., & Srinivasan, N.. (2014). Correlation between local structural dynamics of proteins inferred from nmr ensembles and evolutionary dynamics of homologues of known structure. J biomol struct dyn, 32(5), 751-8. doi:10.1080/07391102.2013.789989
    [BibTeX] [Abstract]

    Conformational changes in proteins are extremely important for their biochemical functions. Correlation between inherent conformational variations in a protein and conformational differences in its homologues of known structure is still unclear. In this study, we have used a structural alphabet called Protein Blocks (PBs). PBs are used to perform abstraction of protein 3-D structures into a 1-D strings of 16 alphabets (a-p) based on dihedral angles of overlapping pentapeptides. We have analyzed the variations in local conformations in terms of PBs represented in the ensembles of 801 protein structures determined using NMR spectroscopy. In the analysis of concatenated data over all the residues in all the NMR ensembles, we observe that the overall nature of inherent local structural variations in NMR ensembles is similar to the nature of local structural differences in homologous proteins with a high correlation coefficient of .94. High correlation at the alignment positions corresponding to helical and β-sheet regions is only expected. However, the correlation coefficient by considering only the loop regions is also quite high (.91). Surprisingly, segregated position-wise analysis shows that this high correlation does not hold true to loop regions at the structurally equivalent positions in NMR ensembles and their homologues of known structure. This suggests that the general nature of local structural changes is unique; however most of the local structural variations in loop regions of NMR ensembles do not correlate to their local structural differences at structurally equivalent positions in homologues.

    @article{Mahajan:2014aa,
    abstract = {Conformational changes in proteins are extremely important for their biochemical functions. Correlation between inherent conformational variations in a protein and conformational differences in its homologues of known structure is still unclear. In this study, we have used a structural alphabet called Protein Blocks (PBs). PBs are used to perform abstraction of protein 3-D structures into a 1-D strings of 16 alphabets (a-p) based on dihedral angles of overlapping pentapeptides. We have analyzed the variations in local conformations in terms of PBs represented in the ensembles of 801 protein structures determined using NMR spectroscopy. In the analysis of concatenated data over all the residues in all the NMR ensembles, we observe that the overall nature of inherent local structural variations in NMR ensembles is similar to the nature of local structural differences in homologous proteins with a high correlation coefficient of .94. High correlation at the alignment positions corresponding to helical and β-sheet regions is only expected. However, the correlation coefficient by considering only the loop regions is also quite high (.91). Surprisingly, segregated position-wise analysis shows that this high correlation does not hold true to loop regions at the structurally equivalent positions in NMR ensembles and their homologues of known structure. This suggests that the general nature of local structural changes is unique; however most of the local structural variations in loop regions of NMR ensembles do not correlate to their local structural differences at structurally equivalent positions in homologues. },
    author = {Mahajan, Swapnil and de Brevern, Alexandre G and Offmann, Bernard and Srinivasan, Narayanaswamy},
    date-added = {2019-10-12 00:55:54 +0200},
    date-modified = {2019-10-12 00:55:54 +0200},
    doi = {10.1080/07391102.2013.789989},
    journal = {J Biomol Struct Dyn},
    journal-full = {Journal of biomolecular structure \& dynamics},
    mesh = {Databases, Protein; Evolution, Molecular; Molecular Dynamics Simulation; Nuclear Magnetic Resonance, Biomolecular; Protein Conformation; Proteins; Sequence Alignment; Sequence Homology, Amino Acid},
    number = {5},
    pages = {751-8},
    pmid = {23730714},
    pst = {ppublish},
    title = {Correlation between local structural dynamics of proteins inferred from NMR ensembles and evolutionary dynamics of homologues of known structure},
    volume = {32},
    year = {2014},
    Bdsk-Url-1 = {https://doi.org/10.1080/07391102.2013.789989}}

  • Manoharan, M., Fuchs, P. F. J., Sowdhamini, R., & Offmann, B.. (2014). Insights on ph-dependent conformational changes of mosquito odorant binding proteins by molecular dynamics simulations. J biomol struct dyn, 32(11), 1742-51. doi:10.1080/07391102.2013.834118
    [BibTeX] [Abstract]

    Chemical recognition plays an important role for the survival and reproduction of many insect species. Odorant binding proteins (OBPs) are the primary components of the insect olfactory mechanism and have been documented to play an important role in the host-seeking mechanism of mosquitoes. They are “transport proteins” believed to transport odorant molecules from the external environment to their respective membrane targets, the olfactory receptors. The mechanism by which this transport occurs in mosquitoes remains a conundrum in this field. Nevertheless, OBPs have proved to be amenable to conformational changes mediated by a pH change in other insect species. In this paper, the effect of pH on the conformational flexibility of mosquito OBPs is assessed computationally using molecular dynamics simulations of a mosquito OBP “CquiOBP1” bound to its pheromone 3OG (PDB ID: 3OGN). Conformational twist of a loop, driven by a set of well-characterized changes in intramolecular interactions of the loop, is demonstrated. The concomitant (i) closure of what is believed to be the entrance of the binding pocket, (ii) expansion of what could be an exit site, and (iii) migration of the ligand towards this putative exit site provide preliminary insights into the mechanism of ligand binding and release of these proteins in mosquitoes. The correlation of our results with previous experimental observations based on NMR studies help us provide a cardinal illustration on one of the probable dynamics and mechanism by which certain mosquito OBPs could deliver their ligand to their membrane-bound receptors at specific pH conditions.

    @article{Manoharan:2014aa,
    abstract = {Chemical recognition plays an important role for the survival and reproduction of many insect species. Odorant binding proteins (OBPs) are the primary components of the insect olfactory mechanism and have been documented to play an important role in the host-seeking mechanism of mosquitoes. They are "transport proteins" believed to transport odorant molecules from the external environment to their respective membrane targets, the olfactory receptors. The mechanism by which this transport occurs in mosquitoes remains a conundrum in this field. Nevertheless, OBPs have proved to be amenable to conformational changes mediated by a pH change in other insect species. In this paper, the effect of pH on the conformational flexibility of mosquito OBPs is assessed computationally using molecular dynamics simulations of a mosquito OBP "CquiOBP1" bound to its pheromone 3OG (PDB ID: 3OGN). Conformational twist of a loop, driven by a set of well-characterized changes in intramolecular interactions of the loop, is demonstrated. The concomitant (i) closure of what is believed to be the entrance of the binding pocket, (ii) expansion of what could be an exit site, and (iii) migration of the ligand towards this putative exit site provide preliminary insights into the mechanism of ligand binding and release of these proteins in mosquitoes. The correlation of our results with previous experimental observations based on NMR studies help us provide a cardinal illustration on one of the probable dynamics and mechanism by which certain mosquito OBPs could deliver their ligand to their membrane-bound receptors at specific pH conditions. },
    author = {Manoharan, Malini and Fuchs, Patrick F J and Sowdhamini, Ramanathan and Offmann, Bernard},
    date-added = {2019-10-12 00:55:49 +0200},
    date-modified = {2019-10-12 00:55:49 +0200},
    doi = {10.1080/07391102.2013.834118},
    journal = {J Biomol Struct Dyn},
    journal-full = {Journal of biomolecular structure \& dynamics},
    keywords = {dynamics; ligand binding; mosquito; odorant binding protein; pH},
    mesh = {Animals; Binding Sites; Culicidae; Hydrogen-Ion Concentration; Insect Proteins; Molecular Dynamics Simulation; Pheromones; Protein Conformation; Receptors, Odorant},
    number = {11},
    pages = {1742-51},
    pmid = {24028686},
    pst = {ppublish},
    title = {Insights on pH-dependent conformational changes of mosquito odorant binding proteins by molecular dynamics simulations},
    volume = {32},
    year = {2014},
    Bdsk-Url-1 = {https://doi.org/10.1080/07391102.2013.834118}}

2013

  • Manoharan, M., Ng Fuk Chong, M., Va{“i}tinadapoulé, A., Frumence, E., Sowdhamini, R., & Offmann, B.. (2013). Comparative genomics of odorant binding proteins in anopheles gambiae, aedes aegypti, and culex quinquefasciatus. Genome biol evol, 5(1), 163-80. doi:10.1093/gbe/evs131
    [BibTeX] [Abstract]

    About 1 million people in the world die each year from diseases spread by mosquitoes, and understanding the mechanism of host identification by the mosquitoes through olfaction is at stake. The role of odorant binding proteins (OBPs) in the primary molecular events of olfaction in mosquitoes is becoming an important focus of biological research in this area. Here, we present a comprehensive comparative genomics study of OBPs in the three disease-transmitting mosquito species Anopheles gambiae, Aedes aegypti, and Culex quinquefasciatus starting with the identification of 110 new OBPs in these three genomes. We have characterized their genomic distribution and orthologous and phylogenetic relationships. The diversity and expansion observed with respect to the Aedes and Culex genomes suggests that the OBP gene family acquired functional diversity concurrently with functional constraints posed on these two species. Sequences with unique features have been characterized such as the “two-domain OBPs” (previously known as Atypical OBPs) and “MinusC OBPs” in mosquito genomes. The extensive comparative genomics featured in this work hence provides useful primary insights into the role of OBPs in the molecular adaptations of mosquito olfactory system and could provide more clues for the identification of potential targets for insect repellants and attractants.

    @article{Manoharan:2013ab,
    abstract = {About 1 million people in the world die each year from diseases spread by mosquitoes, and understanding the mechanism of host identification by the mosquitoes through olfaction is at stake. The role of odorant binding proteins (OBPs) in the primary molecular events of olfaction in mosquitoes is becoming an important focus of biological research in this area. Here, we present a comprehensive comparative genomics study of OBPs in the three disease-transmitting mosquito species Anopheles gambiae, Aedes aegypti, and Culex quinquefasciatus starting with the identification of 110 new OBPs in these three genomes. We have characterized their genomic distribution and orthologous and phylogenetic relationships. The diversity and expansion observed with respect to the Aedes and Culex genomes suggests that the OBP gene family acquired functional diversity concurrently with functional constraints posed on these two species. Sequences with unique features have been characterized such as the "two-domain OBPs" (previously known as Atypical OBPs) and "MinusC OBPs" in mosquito genomes. The extensive comparative genomics featured in this work hence provides useful primary insights into the role of OBPs in the molecular adaptations of mosquito olfactory system and could provide more clues for the identification of potential targets for insect repellants and attractants.},
    author = {Manoharan, Malini and Ng Fuk Chong, Matthieu and Va{\"\i}tinadapoul{\'e}, Aurore and Frumence, Etienne and Sowdhamini, Ramanathan and Offmann, Bernard},
    date-added = {2019-10-12 00:55:54 +0200},
    date-modified = {2019-10-12 00:55:54 +0200},
    doi = {10.1093/gbe/evs131},
    journal = {Genome Biol Evol},
    journal-full = {Genome biology and evolution},
    mesh = {Adaptation, Physiological; Aedes; Animals; Anopheles; Culex; Genome, Insect; Genomics; Phylogeny; Protein Structure, Tertiary; Receptors, Odorant},
    number = {1},
    pages = {163-80},
    pmc = {PMC3595023},
    pmid = {23292137},
    pst = {ppublish},
    title = {Comparative genomics of odorant binding proteins in Anopheles gambiae, Aedes aegypti, and Culex quinquefasciatus},
    volume = {5},
    year = {2013},
    Bdsk-Url-1 = {https://doi.org/10.1093/gbe/evs131}}

  • Mahajan, S., Agarwal, G., Iftekhar, M., Offmann, B., de Brevern, A. G., & Srinivasan, N.. (2013). Dosa: database of structural alignments. Database (oxford), 2013, bat048. doi:10.1093/database/bat048
    [BibTeX] [Abstract]

    Protein structure alignment is a crucial step in protein structure-function analysis. Despite the advances in protein structure alignment algorithms, some of the local conformationally similar regions are mislabeled as structurally variable regions (SVRs). These regions are not well superimposed because of differences in their spatial orientations. The Database of Structural Alignments (DoSA) addresses this gap in identification of local structural similarities obscured in global protein structural alignments by realigning SVRs using an algorithm based on protein blocks. A set of protein blocks is a structural alphabet that abstracts protein structures into 16 unique local structural motifs. DoSA provides unique information about 159,780 conformationally similar and 56,140 conformationally dissimilar SVRs in 74 705 pairwise structural alignments of homologous proteins. The information provided on conformationally similar and dissimilar SVRs can be helpful to model loop regions. It is also conceivable that conformationally similar SVRs with conserved residues could potentially contribute toward functional integrity of homologues, and hence identifying such SVRs could be helpful in understanding the structural basis of protein function. Database URL: http://bo-protscience.fr/dosa/

    @article{Mahajan:2013aa,
    abstract = {Protein structure alignment is a crucial step in protein structure-function analysis. Despite the advances in protein structure alignment algorithms, some of the local conformationally similar regions are mislabeled as structurally variable regions (SVRs). These regions are not well superimposed because of differences in their spatial orientations. The Database of Structural Alignments (DoSA) addresses this gap in identification of local structural similarities obscured in global protein structural alignments by realigning SVRs using an algorithm based on protein blocks. A set of protein blocks is a structural alphabet that abstracts protein structures into 16 unique local structural motifs. DoSA provides unique information about 159,780 conformationally similar and 56,140 conformationally dissimilar SVRs in 74 705 pairwise structural alignments of homologous proteins. The information provided on conformationally similar and dissimilar SVRs can be helpful to model loop regions. It is also conceivable that conformationally similar SVRs with conserved residues could potentially contribute toward functional integrity of homologues, and hence identifying such SVRs could be helpful in understanding the structural basis of protein function. Database URL: http://bo-protscience.fr/dosa/},
    author = {Mahajan, Swapnil and Agarwal, Garima and Iftekhar, Mohammed and Offmann, Bernard and de Brevern, Alexandre G and Srinivasan, Narayanaswamy},
    date-added = {2019-10-12 00:55:53 +0200},
    date-modified = {2019-10-12 00:55:53 +0200},
    doi = {10.1093/database/bat048},
    journal = {Database (Oxford)},
    journal-full = {Database : the journal of biological databases and curation},
    mesh = {Access to Information; Amino Acid Sequence; Databases, Protein; Models, Molecular; Molecular Sequence Data; Proteins; Statistics as Topic; Structural Homology, Protein},
    pages = {bat048},
    pmc = {PMC3708618},
    pmid = {23846594},
    pst = {epublish},
    title = {DoSA: Database of Structural Alignments},
    volume = {2013},
    year = {2013},
    Bdsk-Url-1 = {https://doi.org/10.1093/database/bat048}}

  • Manoharan, M., Sankar, K., Offmann, B., & Ramanathan, S.. (2013). Association of putative members to family of mosquito odorant binding proteins: scoring scheme using fuzzy functional templates and cys residue positions. Bioinform biol insights, 7, 231-51. doi:10.4137/BBI.S11096
    [BibTeX] [Abstract]

    Proteins may be related to each other very specifically as homologous subfamilies. Proteins can also be related to diverse proteins at the super family level. It has become highly important to characterize the existing sequence databases by their signatures to facilitate the function annotation of newly added sequences. The algorithm described here uses a scheme for the classification of odorant binding proteins on the basis of functional residues and Cys-pairing. The cysteine-based scoring scheme not only helps in unambiguously identifying families like odorant binding proteins (OBPs), but also aids in their classification at the subfamily level with reliable accuracy. The algorithm was also applied to yet another cysteine-rich family, where similar accuracy was observed that ensures the application of the protocol to other families.

    @article{Manoharan:2013aa,
    abstract = {Proteins may be related to each other very specifically as homologous subfamilies. Proteins can also be related to diverse proteins at the super family level. It has become highly important to characterize the existing sequence databases by their signatures to facilitate the function annotation of newly added sequences. The algorithm described here uses a scheme for the classification of odorant binding proteins on the basis of functional residues and Cys-pairing. The cysteine-based scoring scheme not only helps in unambiguously identifying families like odorant binding proteins (OBPs), but also aids in their classification at the subfamily level with reliable accuracy. The algorithm was also applied to yet another cysteine-rich family, where similar accuracy was observed that ensures the application of the protocol to other families. },
    author = {Manoharan, Malini and Sankar, Kannan and Offmann, Bernard and Ramanathan, Sowdhamini},
    date-added = {2019-10-12 00:55:52 +0200},
    date-modified = {2019-10-12 00:55:52 +0200},
    doi = {10.4137/BBI.S11096},
    journal = {Bioinform Biol Insights},
    journal-full = {Bioinformatics and biology insights},
    keywords = {Classification of proteins; Functionally important residues; Ligand binding residues; cysteine-based scoring scheme},
    pages = {231-51},
    pmc = {PMC3728099},
    pmid = {23908587},
    pst = {epublish},
    title = {Association of putative members to family of mosquito odorant binding proteins: scoring scheme using fuzzy functional templates and cys residue positions},
    volume = {7},
    year = {2013},
    Bdsk-Url-1 = {https://doi.org/10.4137/BBI.S11096}}

2011

  • Chilamakuri, C. S. R., Joshi, A., Rani, S. S., Offmann, B., & Sowdhamini, R.. (2011). Cross-genome comparisons of newly identified domains in mycoplasma gallisepticum and domain architectures with other mycoplasma species. Comparative and functional genomics, 2011. doi:10.1155/2011/878973
    [BibTeX] [Abstract]

    Accurate functional annotation of protein sequences is hampered by important factors such as the failure of sequence search methods to identify relationships and the inherent diversity in function of proteins related at low sequence similarities. Earlier, we had employed intermediate sequence search approach to establish new domain relationships in the unassigned regions of gene products at the whole genome level by taking Mycoplasma gallisepticum as a specific example and established new domain relationships. In this paper, we report a detailed comparison of the conservation status of the domain and domain architectures of the gene products that bear our newly predicted domains amongst 14 other Mycoplasma genomes and reported the probable implications for the organisms. Some of the domain associations, observed in Mycoplasma that afflict humans and other non-human primates, are involved in regulation of solute transport and DNA binding suggesting specific modes of host-pathogen interactions.

    @article{Chilamakuri:2011aa,
    abstract = {Accurate functional annotation of protein sequences is hampered by important factors such as the failure of sequence search methods to identify relationships and the inherent diversity in function of proteins related at low sequence similarities. Earlier, we had employed intermediate sequence search approach to establish new domain relationships in the unassigned regions of gene products at the whole genome level by taking Mycoplasma gallisepticum as a specific example and established new domain relationships. In this paper, we report a detailed comparison of the conservation status of the domain and domain architectures of the gene products that bear our newly predicted domains amongst 14 other Mycoplasma genomes and reported the probable implications for the organisms. Some of the domain associations, observed in Mycoplasma that afflict humans and other non-human primates, are involved in regulation of solute transport and DNA binding suggesting specific modes of host-pathogen interactions.},
    author = {Chilamakuri, Chandra Sekhar Reddy and Joshi, Adwait and Rani, Sane Sudha and Offmann, Bernard and Sowdhamini, R},
    date-added = {2019-10-12 00:55:55 +0200},
    date-modified = {2020-02-23 21:13:04 +0100},
    doi = {10.1155/2011/878973},
    journal = {Comparative and functional genomics},
    journal-full = {Comparative and functional genomics},
    pmc = {PMC3155973},
    pmid = {21860605},
    pst = {ppublish},
    title = {Cross-Genome Comparisons of Newly Identified Domains in Mycoplasma gallisepticum and Domain Architectures with Other Mycoplasma species},
    volume = {2011},
    year = {2011},
    Bdsk-Url-1 = {https://doi.org/10.1155/2011/878973}}

2010

  • Joseph, A. P., Agarwal, G., Mahajan, S., Gelly, J., Swapna, L. S., Offmann, B., Cadet, F., Bornot, A., Tyagi, M., Valadié, H., Schneider, B., Etchebest, C., Srinivasan, N., & De Brevern, A. G.. (2010). A short survey on protein blocks. Biophys rev, 2(3), 137-147. doi:10.1007/s12551-010-0036-1
    [BibTeX] [Abstract]

    Protein structures are classically described in terms of secondary structures. Even if the regular secondary structures have relevant physical meaning, their recognition from atomic coordinates has some important limitations such as uncertainties in the assignment of boundaries of helical and β-strand regions. Further, on an average about 50% of all residues are assigned to an irregular state, i.e., the coil. Thus different research teams have focused on abstracting conformation of protein backbone in the localized short stretches. Using different geometric measures, local stretches in protein structures are clustered in a chosen number of states. A prototype representative of the local structures in each cluster is generally defined. These libraries of local structures prototypes are named as “structural alphabets”. We have developed a structural alphabet, named Protein Blocks, not only to approximate the protein structure, but also to predict them from sequence. Since its development, we and other teams have explored numerous new research fields using this structural alphabet. We review here some of the most interesting applications.

    @article{Joseph:2010aa,
    abstract = {Protein structures are classically described in terms of secondary structures. Even if the regular secondary structures have relevant physical meaning, their recognition from atomic coordinates has some important limitations such as uncertainties in the assignment of boundaries of helical and β-strand regions. Further, on an average about 50% of all residues are assigned to an irregular state, i.e., the coil. Thus different research teams have focused on abstracting conformation of protein backbone in the localized short stretches. Using different geometric measures, local stretches in protein structures are clustered in a chosen number of states. A prototype representative of the local structures in each cluster is generally defined. These libraries of local structures prototypes are named as "structural alphabets". We have developed a structural alphabet, named Protein Blocks, not only to approximate the protein structure, but also to predict them from sequence. Since its development, we and other teams have explored numerous new research fields using this structural alphabet. We review here some of the most interesting applications.},
    author = {Joseph, Agnel Praveen and Agarwal, Garima and Mahajan, Swapnil and Gelly, Jean-Christophe and Swapna, Lakshmipuram S and Offmann, Bernard and Cadet, Fr{\'e}d{\'e}ric and Bornot, Aur{\'e}lie and Tyagi, Manoj and Valadi{\'e}, H{\'e}l{\`e}ne and Schneider, Bohdan and Etchebest, Catherine and Srinivasan, Narayanaswamy and De Brevern, Alexandre G},
    date-added = {2019-10-12 00:55:56 +0200},
    date-modified = {2019-10-12 00:55:56 +0200},
    doi = {10.1007/s12551-010-0036-1},
    journal = {Biophys Rev},
    journal-full = {Biophysical reviews},
    month = {Aug},
    number = {3},
    pages = {137-147},
    pmc = {PMC3124139},
    pmid = {21731588},
    pst = {ppublish},
    title = {A short survey on protein blocks},
    volume = {2},
    year = {2010},
    Bdsk-Url-1 = {https://doi.org/10.1007/s12551-010-0036-1}}

  • Reddy, C. C., Rani, S. S., Offmann, B., & Sowdhamini, R.. (2010). Systematic search for putative new domain families in mycoplasma gallisepticum genome. Bmc res notes, 3, 98. doi:10.1186/1756-0500-3-98
    [BibTeX] [Abstract]

    BACKGROUND: Protein domains are the fundamental units of protein structure, function and evolution. The delineation of different domains in proteins is important for classification, understanding of structure, function and evolution. The delineation of protein domains within a polypeptide chain, namely at the genome scale, can be achieved in several ways but may remain problematic in many instances. Difficulties in identifying the domain content of a given sequence arise when the query sequence has no homologues with experimentally determined structure and searching against sequence domain databases also results in insignificant matches. Identification of domains under low sequence identity conditions and lack of structural homologues acquire a crucial importance especially at the genomic scale. FINDINGS: We have developed a new method for the identification of domains in unassigned regions through indirect connections and scaled up its application to the analysis of 434 unassigned regions in 726 protein sequences of Mycoplasma gallisepticum genome. We could establish 71 new domain relationships and probable 63 putative new domain families through intermediate sequences in the unassigned regions, which importantly represent an overall 10% increase in PfamA domain annotation over the direct assignment in this genome. CONCLUSIONS: The systematic analysis of the unassigned regions in the Mycoplasma gallisepticum genome has provided some insight into the possible new domain relationships and putative new domain families. Further investigation of these predicted new domains may prove beneficial in improving the existing domain prediction algorithms.

    @article{Reddy:2010aa,
    abstract = {BACKGROUND: Protein domains are the fundamental units of protein structure, function and evolution. The delineation of different domains in proteins is important for classification, understanding of structure, function and evolution. The delineation of protein domains within a polypeptide chain, namely at the genome scale, can be achieved in several ways but may remain problematic in many instances. Difficulties in identifying the domain content of a given sequence arise when the query sequence has no homologues with experimentally determined structure and searching against sequence domain databases also results in insignificant matches. Identification of domains under low sequence identity conditions and lack of structural homologues acquire a crucial importance especially at the genomic scale.
    FINDINGS: We have developed a new method for the identification of domains in unassigned regions through indirect connections and scaled up its application to the analysis of 434 unassigned regions in 726 protein sequences of Mycoplasma gallisepticum genome. We could establish 71 new domain relationships and probable 63 putative new domain families through intermediate sequences in the unassigned regions, which importantly represent an overall 10% increase in PfamA domain annotation over the direct assignment in this genome.
    CONCLUSIONS: The systematic analysis of the unassigned regions in the Mycoplasma gallisepticum genome has provided some insight into the possible new domain relationships and putative new domain families. Further investigation of these predicted new domains may prove beneficial in improving the existing domain prediction algorithms.},
    author = {Reddy, Chilamakuri Cs and Rani, Sane Sudha and Offmann, Bernard and Sowdhamini, R},
    date-added = {2019-10-12 00:55:56 +0200},
    date-modified = {2019-10-12 00:55:56 +0200},
    doi = {10.1186/1756-0500-3-98},
    journal = {BMC Res Notes},
    journal-full = {BMC research notes},
    month = {Apr},
    pages = {98},
    pmc = {PMC2865477},
    pmid = {20384986},
    pst = {epublish},
    title = {Systematic search for putative new domain families in Mycoplasma gallisepticum genome},
    volume = {3},
    year = {2010},
    Bdsk-Url-1 = {https://doi.org/10.1186/1756-0500-3-98}}

  • Groben, R., Kaloudas, D., Raines, C. A., Offmann, B., Maberly, S. C., & Gontero, B.. (2010). Comparative sequence analysis of cp12, a small protein involved in the formation of a calvin cycle complex in photosynthetic organisms. Photosynth res, 103(3), 183-94. doi:10.1007/s11120-010-9542-z
    [BibTeX] [Abstract]

    CP12, a small intrinsically unstructured protein, plays an important role in the regulation of the Calvin cycle by forming a complex with phosphoribulokinase (PRK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). An extensive search in databases revealed 129 protein sequences from, higher plants, mosses and liverworts, different groups of eukaryotic algae and cyanobacteria. CP12 was identified throughout the Plantae, apart from in the Prasinophyceae. Within the Chromalveolata, two putative CP12 proteins have been found in the genomes of the diatom Thalassiosira pseudonana and the haptophyte Emiliania huxleyi, but specific searches in further chromalveolate genomes or EST datasets did not reveal any CP12 sequences in other Prymnesiophyceae, Dinophyceae or Pelagophyceae. A species from the Euglenophyceae within the Excavata also appeared to lack CP12. Phylogenetic analysis showed a clear separation into a number of higher taxonomic clades and among different forms of CP12 in higher plants. Cyanobacteria, Chlorophyceae, Rhodophyta and Glaucophyceae, Bryophyta, and the CP12-3 forms in higher plants all form separate clades. The degree of disorder of CP12 was higher in higher plants than in the eukaryotic algae and cyanobacteria apart from the green algal class Mesostigmatophyceae, which is ancestral to the streptophytes. This suggests that CP12 has evolved to become more flexible and possibly take on more general roles. Different features of the CP12 sequences in the different taxonomic groups and their potential functions and interactions in the Calvin cycle are discussed.

    @article{Groben:2010aa,
    abstract = {CP12, a small intrinsically unstructured protein, plays an important role in the regulation of the Calvin cycle by forming a complex with phosphoribulokinase (PRK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). An extensive search in databases revealed 129 protein sequences from, higher plants, mosses and liverworts, different groups of eukaryotic algae and cyanobacteria. CP12 was identified throughout the Plantae, apart from in the Prasinophyceae. Within the Chromalveolata, two putative CP12 proteins have been found in the genomes of the diatom Thalassiosira pseudonana and the haptophyte Emiliania huxleyi, but specific searches in further chromalveolate genomes or EST datasets did not reveal any CP12 sequences in other Prymnesiophyceae, Dinophyceae or Pelagophyceae. A species from the Euglenophyceae within the Excavata also appeared to lack CP12. Phylogenetic analysis showed a clear separation into a number of higher taxonomic clades and among different forms of CP12 in higher plants. Cyanobacteria, Chlorophyceae, Rhodophyta and Glaucophyceae, Bryophyta, and the CP12-3 forms in higher plants all form separate clades. The degree of disorder of CP12 was higher in higher plants than in the eukaryotic algae and cyanobacteria apart from the green algal class Mesostigmatophyceae, which is ancestral to the streptophytes. This suggests that CP12 has evolved to become more flexible and possibly take on more general roles. Different features of the CP12 sequences in the different taxonomic groups and their potential functions and interactions in the Calvin cycle are discussed.},
    author = {Groben, Ren{\'e} and Kaloudas, Dimitrios and Raines, Christine A and Offmann, Bernard and Maberly, Stephen C and Gontero, Brigitte},
    date-added = {2019-10-12 00:55:57 +0200},
    date-modified = {2019-10-12 00:55:57 +0200},
    doi = {10.1007/s11120-010-9542-z},
    journal = {Photosynth Res},
    journal-full = {Photosynthesis research},
    mesh = {Algal Proteins; Amino Acid Sequence; Eukaryota; Expressed Sequence Tags; Genome; Molecular Sequence Data; Photosynthesis; Phylogeny; Plant Proteins; Plants; Sequence Analysis, Protein; Sequence Homology, Amino Acid},
    month = {Mar},
    number = {3},
    pages = {183-94},
    pmid = {20224939},
    pst = {ppublish},
    title = {Comparative sequence analysis of CP12, a small protein involved in the formation of a Calvin cycle complex in photosynthetic organisms},
    volume = {103},
    year = {2010},
    Bdsk-Url-1 = {https://doi.org/10.1007/s11120-010-9542-z}}

2009

  • Tyagi, M., Bornot, A., Offmann, B., & de Brevern, A. G.. (2009). Analysis of loop boundaries using different local structure assignment methods. Protein sci, 18(9), 1869-81. doi:10.1002/pro.198
    [BibTeX] [Abstract]

    Loops connect regular secondary structures. In many instances, they are known to play important biological roles. Analysis and prediction of loop conformations depend directly on the definition of repetitive structures. Nonetheless, the secondary structure assignment methods (SSAMs) often lead to divergent assignments. In this study, we analyzed, both structure and sequence point of views, how the divergence between different SSAMs affect boundary definitions of loops connecting regular secondary structures. The analysis of SSAMs underlines that no clear consensus between the different SSAMs can be easily found. Because these latter greatly influence the loop boundary definitions, important variations are indeed observed, that is, capping positions are shifted between different SSAMs. On the other hand, our results show that the sequence information in these capping regions are more stable than expected, and, classical and equivalent sequence patterns were found for most of the SSAMs. This is, to our knowledge, the most exhaustive survey in this field as (i) various databank have been used leading to similar results without implication of protein redundancy and (ii) the first time various SSAMs have been used. This work hence gives new insights into the difficult question of assignment of repetitive structures and addresses the issue of loop boundaries definition. Although SSAMs give very different local structure assignments capping sequence patterns remain efficiently stable.

    @article{Tyagi:2009ab,
    abstract = {Loops connect regular secondary structures. In many instances, they are known to play important biological roles. Analysis and prediction of loop conformations depend directly on the definition of repetitive structures. Nonetheless, the secondary structure assignment methods (SSAMs) often lead to divergent assignments. In this study, we analyzed, both structure and sequence point of views, how the divergence between different SSAMs affect boundary definitions of loops connecting regular secondary structures. The analysis of SSAMs underlines that no clear consensus between the different SSAMs can be easily found. Because these latter greatly influence the loop boundary definitions, important variations are indeed observed, that is, capping positions are shifted between different SSAMs. On the other hand, our results show that the sequence information in these capping regions are more stable than expected, and, classical and equivalent sequence patterns were found for most of the SSAMs. This is, to our knowledge, the most exhaustive survey in this field as (i) various databank have been used leading to similar results without implication of protein redundancy and (ii) the first time various SSAMs have been used. This work hence gives new insights into the difficult question of assignment of repetitive structures and addresses the issue of loop boundaries definition. Although SSAMs give very different local structure assignments capping sequence patterns remain efficiently stable.},
    author = {Tyagi, Manoj and Bornot, Aur{\'e}lie and Offmann, Bernard and de Brevern, Alexandre G},
    date-added = {2019-10-12 00:55:59 +0200},
    date-modified = {2019-10-12 00:55:59 +0200},
    doi = {10.1002/pro.198},
    journal = {Protein Sci},
    journal-full = {Protein science : a publication of the Protein Society},
    mesh = {Amino Acid Sequence; Computer Simulation; Databases, Protein; Methyltransferases; Models, Molecular; Protein Conformation; Protein Structure, Secondary; Proteins},
    month = {Sep},
    number = {9},
    pages = {1869-81},
    pmc = {PMC2777362},
    pmid = {19606500},
    pst = {ppublish},
    title = {Analysis of loop boundaries using different local structure assignment methods},
    volume = {18},
    year = {2009},
    Bdsk-Url-1 = {https://doi.org/10.1002/pro.198}}

  • Tyagi, M., Bornot, A., Offmann, B., & de Brevern, A. G.. (2009). Protein short loop prediction in terms of a structural alphabet. Comput biol chem, 33(4), 329-33. doi:10.1016/j.compbiolchem.2009.06.002
    [BibTeX] [Abstract]

    Loops connect regular secondary structures. In many instances, they are known to play crucial biological roles. To bypass the limitation of secondary structure description, we previously defined a structural alphabet composed of 16 structural prototypes, called Protein Blocks (PBs). It leads to an accurate description of every region of 3D protein backbones and has been used in local structure prediction. In the present study, we used our structural alphabet to predict the loops connecting two repetitive structures. Thus, we showed interest to take into account the flanking regions, leading to prediction rate improvement up to 19.8%, but we also underline the sensitivity of such an approach. This research can be used to propose different structures for the loops and to probe and sample their flexibility. It is a useful tool for ab initio loop prediction and leads to insights into flexible docking approach.

    @article{Tyagi:2009aa,
    abstract = {Loops connect regular secondary structures. In many instances, they are known to play crucial biological roles. To bypass the limitation of secondary structure description, we previously defined a structural alphabet composed of 16 structural prototypes, called Protein Blocks (PBs). It leads to an accurate description of every region of 3D protein backbones and has been used in local structure prediction. In the present study, we used our structural alphabet to predict the loops connecting two repetitive structures. Thus, we showed interest to take into account the flanking regions, leading to prediction rate improvement up to 19.8%, but we also underline the sensitivity of such an approach. This research can be used to propose different structures for the loops and to probe and sample their flexibility. It is a useful tool for ab initio loop prediction and leads to insights into flexible docking approach.},
    author = {Tyagi, Manoj and Bornot, Aur{\'e}lie and Offmann, Bernard and de Brevern, Alexandre G},
    date-added = {2019-10-12 00:55:58 +0200},
    date-modified = {2019-10-12 00:55:58 +0200},
    doi = {10.1016/j.compbiolchem.2009.06.002},
    journal = {Comput Biol Chem},
    journal-full = {Computational biology and chemistry},
    mesh = {Computer Simulation; Databases, Protein; Protein Structure, Secondary; Proteins},
    month = {Aug},
    number = {4},
    pages = {329-33},
    pmid = {19625218},
    pst = {ppublish},
    title = {Protein short loop prediction in terms of a structural alphabet},
    volume = {33},
    year = {2009},
    Bdsk-Url-1 = {https://doi.org/10.1016/j.compbiolchem.2009.06.002}}

  • Sandhya, S., Rani, S. S., Pankaj, B., Govind, M. K., Offmann, B., Srinivasan, N., & Sowdhamini, R.. (2009). Length variations amongst protein domain superfamilies and consequences on structure and function. Plos one, 4(3), e4981.
    [BibTeX]
    @article{sandhya2009length,
    author = {Sandhya, Sankaran and Rani, Saane Sudha and Pankaj, Barah and Govind, Madabosse Kande and Offmann, Bernard and Srinivasan, Narayanaswamy and Sowdhamini, Ramanathan},
    journal = {PLoS One},
    number = {3},
    pages = {e4981},
    publisher = {Public Library of Science},
    title = {Length variations amongst protein domain superfamilies and consequences on structure and function},
    volume = {4},
    year = {2009}}

2008

  • Thangudu, R. R., Manoharan, M., Srinivasan, N., Cadet, F., Sowdhamini, R., & Offmann, B.. (2008). Analysis on conservation of disulphide bonds and their structural features in homologous protein domain families. Bmc struct biol, 8, 55. doi:10.1186/1472-6807-8-55
    [BibTeX] [Abstract]

    BACKGROUND: Disulphide bridges are well known to play key roles in stability, folding and functions of proteins. Introduction or deletion of disulphides by site-directed mutagenesis have produced varying effects on stability and folding depending upon the protein and location of disulphide in the 3-D structure. Given the lack of complete understanding it is worthwhile to learn from an analysis of extent of conservation of disulphides in homologous proteins. We have also addressed the question of what structural interactions replaces a disulphide in a homologue in another homologue. RESULTS: Using a dataset involving 34,752 pairwise comparisons of homologous protein domains corresponding to 300 protein domain families of known 3-D structures, we provide a comprehensive analysis of extent of conservation of disulphide bridges and their structural features. We report that only 54% of all the disulphide bonds compared between the homologous pairs are conserved, even if, a small fraction of the non-conserved disulphides do include cytoplasmic proteins. Also, only about one fourth of the distinct disulphides are conserved in all the members in protein families. We note that while conservation of disulphide is common in many families, disulphide bond mutations are quite prevalent. Interestingly, we note that there is no clear relationship between sequence identity between two homologous proteins and disulphide bond conservation. Our analysis on structural features at the sites where cysteines forming disulphide in one homologue are replaced by non-Cys residues show that the elimination of a disulphide in a homologue need not always result in stabilizing interactions between equivalent residues. CONCLUSION: We observe that in the homologous proteins, disulphide bonds are conserved only to a modest extent. Very interestingly, we note that extent of conservation of disulphide in homologous proteins is unrelated to the overall sequence identity between homologues. The non-conserved disulphides are often associated with variable structural features that were recruited to be associated with differentiation or specialisation of protein function.

    @article{Thangudu:2008aa,
    abstract = {BACKGROUND: Disulphide bridges are well known to play key roles in stability, folding and functions of proteins. Introduction or deletion of disulphides by site-directed mutagenesis have produced varying effects on stability and folding depending upon the protein and location of disulphide in the 3-D structure. Given the lack of complete understanding it is worthwhile to learn from an analysis of extent of conservation of disulphides in homologous proteins. We have also addressed the question of what structural interactions replaces a disulphide in a homologue in another homologue.
    RESULTS: Using a dataset involving 34,752 pairwise comparisons of homologous protein domains corresponding to 300 protein domain families of known 3-D structures, we provide a comprehensive analysis of extent of conservation of disulphide bridges and their structural features. We report that only 54% of all the disulphide bonds compared between the homologous pairs are conserved, even if, a small fraction of the non-conserved disulphides do include cytoplasmic proteins. Also, only about one fourth of the distinct disulphides are conserved in all the members in protein families. We note that while conservation of disulphide is common in many families, disulphide bond mutations are quite prevalent. Interestingly, we note that there is no clear relationship between sequence identity between two homologous proteins and disulphide bond conservation. Our analysis on structural features at the sites where cysteines forming disulphide in one homologue are replaced by non-Cys residues show that the elimination of a disulphide in a homologue need not always result in stabilizing interactions between equivalent residues.
    CONCLUSION: We observe that in the homologous proteins, disulphide bonds are conserved only to a modest extent. Very interestingly, we note that extent of conservation of disulphide in homologous proteins is unrelated to the overall sequence identity between homologues. The non-conserved disulphides are often associated with variable structural features that were recruited to be associated with differentiation or specialisation of protein function.},
    author = {Thangudu, Ratna R and Manoharan, Malini and Srinivasan, N and Cadet, Fr{\'e}d{\'e}ric and Sowdhamini, R and Offmann, Bernard},
    date-added = {2019-10-12 00:56:02 +0200},
    date-modified = {2019-10-12 00:56:02 +0200},
    doi = {10.1186/1472-6807-8-55},
    journal = {BMC Struct Biol},
    journal-full = {BMC structural biology},
    mesh = {Conserved Sequence; Cystine; Databases, Protein; Disulfides; Protein Conformation; Protein Structure, Tertiary; Proteins; Sequence Alignment; Solvents; Structural Homology, Protein},
    month = {Dec},
    pages = {55},
    pmc = {PMC2628669},
    pmid = {19111067},
    pst = {epublish},
    title = {Analysis on conservation of disulphide bonds and their structural features in homologous protein domain families},
    volume = {8},
    year = {2008},
    Bdsk-Url-1 = {https://doi.org/10.1186/1472-6807-8-55}}

  • Reddy, C. C. S., Shameer, K., Offmann, B. O., & Sowdhamini, R.. (2008). Pure: a webserver for the prediction of domains in unassigned regions in proteins. Bmc bioinformatics, 9, 281. doi:10.1186/1471-2105-9-281
    [BibTeX] [Abstract]

    BACKGROUND: Protein domains are the structural and functional units of proteins. The ability to parse proteins into different domains is important for effective classification, understanding of protein structure, function, and evolution and is hence biologically relevant. Several computational methods are available to identify domains in the sequence. Domain finding algorithms often employ stringent thresholds to recognize sequence domains. Identification of additional domains can be tedious involving intense computation and manual intervention but can lead to better understanding of overall biological function. In this context, the problem of identifying new domains in the unassigned regions of a protein sequence assumes a crucial importance. RESULTS: We had earlier demonstrated that accumulation of domain information of sequence homologues can substantially aid prediction of new domains. In this paper, we propose a computationally intensive, multi-step bioinformatics protocol as a web server named as PURE (Prediction of Unassigned REgions in proteins) for the detailed examination of stretches of unassigned regions in proteins. Query sequence is processed using different automated filtering steps based on length, presence of coiled-coil regions, transmembrane regions, homologous sequences and percentage of secondary structure content. Later, the filtered sequence segments and their sequence homologues are fed to PSI-BLAST, cd-hit and Hmmpfam. Data from the various programs are integrated and information regarding the probable domains predicted from the sequence is reported. CONCLUSION: We have implemented PURE protocol as a web server for rapid and comprehensive analysis of unassigned regions in the proteins. This server integrates data from different programs and provides information about the domains encoded in the unassigned regions.

    @article{Reddy:2008aa,
    abstract = {BACKGROUND: Protein domains are the structural and functional units of proteins. The ability to parse proteins into different domains is important for effective classification, understanding of protein structure, function, and evolution and is hence biologically relevant. Several computational methods are available to identify domains in the sequence. Domain finding algorithms often employ stringent thresholds to recognize sequence domains. Identification of additional domains can be tedious involving intense computation and manual intervention but can lead to better understanding of overall biological function. In this context, the problem of identifying new domains in the unassigned regions of a protein sequence assumes a crucial importance.
    RESULTS: We had earlier demonstrated that accumulation of domain information of sequence homologues can substantially aid prediction of new domains. In this paper, we propose a computationally intensive, multi-step bioinformatics protocol as a web server named as PURE (Prediction of Unassigned REgions in proteins) for the detailed examination of stretches of unassigned regions in proteins. Query sequence is processed using different automated filtering steps based on length, presence of coiled-coil regions, transmembrane regions, homologous sequences and percentage of secondary structure content. Later, the filtered sequence segments and their sequence homologues are fed to PSI-BLAST, cd-hit and Hmmpfam. Data from the various programs are integrated and information regarding the probable domains predicted from the sequence is reported.
    CONCLUSION: We have implemented PURE protocol as a web server for rapid and comprehensive analysis of unassigned regions in the proteins. This server integrates data from different programs and provides information about the domains encoded in the unassigned regions.},
    author = {Reddy, Chilamakuri C S and Shameer, Khader and Offmann, Bernard O and Sowdhamini, Ramanathan},
    date-added = {2019-10-12 00:56:02 +0200},
    date-modified = {2019-10-12 00:56:02 +0200},
    doi = {10.1186/1471-2105-9-281},
    journal = {BMC Bioinformatics},
    journal-full = {BMC bioinformatics},
    mesh = {Adenylyl Cyclases; Amino Acid Motifs; Animals; Cluster Analysis; Computational Biology; Databases, Protein; Humans; Mycoplasma gallisepticum; Pattern Recognition, Automated; Protein Structure, Tertiary; Sequence Analysis, Protein; Software; Structural Homology, Protein},
    month = {Jun},
    pages = {281},
    pmc = {PMC2474620},
    pmid = {18554415},
    pst = {epublish},
    title = {PURE: a webserver for the prediction of domains in unassigned regions in proteins},
    volume = {9},
    year = {2008},
    Bdsk-Url-1 = {https://doi.org/10.1186/1471-2105-9-281}}

  • Tyagi, M., de Brevern, A. G., Srinivasan, N., & Offmann, B.. (2008). Protein structure mining using a structural alphabet. Proteins, 71(2), 920-37. doi:10.1002/prot.21776
    [BibTeX] [Abstract]

    We present a comprehensive evaluation of a new structure mining method called PB-ALIGN. It is based on the encoding of protein structure as 1D sequence of a combination of 16 short structural motifs or protein blocks (PBs). PBs are short motifs capable of representing most of the local structural features of a protein backbone. Using derived PB substitution matrix and simple dynamic programming algorithm, PB sequences are aligned the same way amino acid sequences to yield structure alignment. PBs are short motifs capable of representing most of the local structural features of a protein backbone. Alignment of these local features as sequence of symbols enables fast detection of structural similarities between two proteins. Ability of the method to characterize and align regions beyond regular secondary structures, for example, N and C caps of helix and loops connecting regular structures, puts it a step ahead of existing methods, which strongly rely on secondary structure elements. PB-ALIGN achieved efficiency of 85% in extracting true fold from a large database of 7259 SCOP domains and was successful in 82% cases to identify true super-family members. On comparison to 13 existing structure comparison/mining methods, PB-ALIGN emerged as the best on general ability test dataset and was at par with methods like YAKUSA and CE on nontrivial test dataset. Furthermore, the proposed method performed well when compared to flexible structure alignment method like FATCAT and outperforms in processing speed (less than 45 s per database scan). This work also establishes a reliable cut-off value for the demarcation of similar folds. It finally shows that global alignment scores of unrelated structures using PBs follow an extreme value distribution. PB-ALIGN is freely available on web server called Protein Block Expert (PBE) at http://bioinformatics.univ-reunion.fr/PBE/.

    @article{Tyagi:2008aa,
    abstract = {We present a comprehensive evaluation of a new structure mining method called PB-ALIGN. It is based on the encoding of protein structure as 1D sequence of a combination of 16 short structural motifs or protein blocks (PBs). PBs are short motifs capable of representing most of the local structural features of a protein backbone. Using derived PB substitution matrix and simple dynamic programming algorithm, PB sequences are aligned the same way amino acid sequences to yield structure alignment. PBs are short motifs capable of representing most of the local structural features of a protein backbone. Alignment of these local features as sequence of symbols enables fast detection of structural similarities between two proteins. Ability of the method to characterize and align regions beyond regular secondary structures, for example, N and C caps of helix and loops connecting regular structures, puts it a step ahead of existing methods, which strongly rely on secondary structure elements. PB-ALIGN achieved efficiency of 85% in extracting true fold from a large database of 7259 SCOP domains and was successful in 82% cases to identify true super-family members. On comparison to 13 existing structure comparison/mining methods, PB-ALIGN emerged as the best on general ability test dataset and was at par with methods like YAKUSA and CE on nontrivial test dataset. Furthermore, the proposed method performed well when compared to flexible structure alignment method like FATCAT and outperforms in processing speed (less than 45 s per database scan). This work also establishes a reliable cut-off value for the demarcation of similar folds. It finally shows that global alignment scores of unrelated structures using PBs follow an extreme value distribution. PB-ALIGN is freely available on web server called Protein Block Expert (PBE) at http://bioinformatics.univ-reunion.fr/PBE/.},
    author = {Tyagi, M and de Brevern, A G and Srinivasan, N and Offmann, B},
    date-added = {2019-10-12 00:56:05 +0200},
    date-modified = {2019-10-12 00:56:05 +0200},
    doi = {10.1002/prot.21776},
    journal = {Proteins},
    journal-full = {Proteins},
    mesh = {Algorithms; Amino Acid Motifs; Amino Acid Sequence; Databases, Protein; Models, Molecular; Protein Folding; Proteins; Sensitivity and Specificity; Sequence Alignment; Sequence Analysis, Protein; Software; src Homology Domains},
    month = {May},
    number = {2},
    pages = {920-37},
    pmid = {18004784},
    pst = {ppublish},
    title = {Protein structure mining using a structural alphabet},
    volume = {71},
    year = {2008},
    Bdsk-Url-1 = {https://doi.org/10.1002/prot.21776}}

  • Sandhya, S., Pankaj, B., Govind, M. K., Offmann, B., Srinivasan, N., & Sowdhamini, R.. (2008). Cusp: an algorithm to distinguish structurally conserved and unconserved regions in protein domain alignments and its application in the study of large length variations. Bmc struct biol, 8, 28. doi:10.1186/1472-6807-8-28
    [BibTeX] [Abstract]

    BACKGROUND: Distantly related proteins adopt and retain similar structural scaffolds despite length variations that could be as much as two-fold in some protein superfamilies. In this paper, we describe an analysis of indel regions that accommodate length variations amongst related proteins. We have developed an algorithm CUSP, to examine multi-membered PASS2 superfamily alignments to identify indel regions in an automated manner. Further, we have used the method to characterize the length, structural type and biochemical features of indels in related protein domains. RESULTS: CUSP, examines protein domain structural alignments to distinguish regions of conserved structure common to related proteins from structurally unconserved regions that vary in length and type of structure. On a non-redundant dataset of 353 domain superfamily alignments from PASS2, we find that ‘length- deviant’ protein superfamilies show > 30% length variation from their average domain length. 60% of additional lengths that occur in indels are short-length structures (< 5 residues) while 6% of indels are > 15 residues in length. Structural types in indels also show class-specific trends. CONCLUSION: The extent of length variation varies across different superfamilies and indels show class-specific trends for preferred lengths and structural types. Such indels of different lengths even within a single protein domain superfamily could have structural and functional consequences that drive their selection, underlying their importance in similarity detection and computational modelling. The availability of systematic algorithms, like CUSP, should enable decision making in a domain superfamily-specific manner.

    @article{Sandhya:2008aa,
    abstract = {BACKGROUND: Distantly related proteins adopt and retain similar structural scaffolds despite length variations that could be as much as two-fold in some protein superfamilies. In this paper, we describe an analysis of indel regions that accommodate length variations amongst related proteins. We have developed an algorithm CUSP, to examine multi-membered PASS2 superfamily alignments to identify indel regions in an automated manner. Further, we have used the method to characterize the length, structural type and biochemical features of indels in related protein domains.
    RESULTS: CUSP, examines protein domain structural alignments to distinguish regions of conserved structure common to related proteins from structurally unconserved regions that vary in length and type of structure. On a non-redundant dataset of 353 domain superfamily alignments from PASS2, we find that 'length- deviant' protein superfamilies show > 30% length variation from their average domain length. 60% of additional lengths that occur in indels are short-length structures (< 5 residues) while 6% of indels are > 15 residues in length. Structural types in indels also show class-specific trends.
    CONCLUSION: The extent of length variation varies across different superfamilies and indels show class-specific trends for preferred lengths and structural types. Such indels of different lengths even within a single protein domain superfamily could have structural and functional consequences that drive their selection, underlying their importance in similarity detection and computational modelling. The availability of systematic algorithms, like CUSP, should enable decision making in a domain superfamily-specific manner.},
    author = {Sandhya, Sankaran and Pankaj, Barah and Govind, Madabosse Kande and Offmann, Bernard and Srinivasan, Narayanaswamy and Sowdhamini, Ramanathan},
    date-added = {2019-10-12 00:56:03 +0200},
    date-modified = {2019-10-12 00:56:03 +0200},
    doi = {10.1186/1472-6807-8-28},
    journal = {BMC Struct Biol},
    journal-full = {BMC structural biology},
    mesh = {Algorithms; Conserved Sequence; Models, Molecular; Protein Conformation; Protein Structure, Tertiary; Proteins; Sequence Alignment},
    month = {May},
    pages = {28},
    pmc = {PMC2423364},
    pmid = {18513436},
    pst = {epublish},
    title = {CUSP: an algorithm to distinguish structurally conserved and unconserved regions in protein domain alignments and its application in the study of large length variations},
    volume = {8},
    year = {2008},
    Bdsk-Url-1 = {https://doi.org/10.1186/1472-6807-8-28}}

2007

  • Thangudu, R. R., Sharma, P., Srinivasan, N., & Offmann, B.. (2007). Analycys: a database for conservation and conformation of disulphide bonds in homologous protein domains. Proteins, 67(2), 255-61. doi:10.1002/prot.21318
    [BibTeX] [Abstract]

    Disulphide bonds in proteins are known to play diverse roles ranging from folding to structure to function. Thorough knowledge of the conservation status and structural state of the disulphide bonds will help in understanding of the differences in homologous proteins. Here we present a database for the analysis of conservation and conformation of disulphide bonds in SCOP structural families. This database has a wide range of applications including mapping of disulphide bond mutation patterns, identification of disulphide bonds important for folding and stabilization, modeling of protein tertiary structures and in protein engineering. The database can be accessed at: http://bioinformatics.univ-reunion.fr/analycys/.

    @article{Thangudu:2007aa,
    abstract = {Disulphide bonds in proteins are known to play diverse roles ranging from folding to structure to function. Thorough knowledge of the conservation status and structural state of the disulphide bonds will help in understanding of the differences in homologous proteins. Here we present a database for the analysis of conservation and conformation of disulphide bonds in SCOP structural families. This database has a wide range of applications including mapping of disulphide bond mutation patterns, identification of disulphide bonds important for folding and stabilization, modeling of protein tertiary structures and in protein engineering. The database can be accessed at: http://bioinformatics.univ-reunion.fr/analycys/.},
    author = {Thangudu, Ratna R and Sharma, Priyanka and Srinivasan, N and Offmann, Bernard},
    date-added = {2019-10-12 00:56:07 +0200},
    date-modified = {2019-10-12 00:56:07 +0200},
    doi = {10.1002/prot.21318},
    journal = {Proteins},
    journal-full = {Proteins},
    mesh = {Conserved Sequence; Databases, Protein; Disulfides; Internet; Mutation; Protein Conformation; Proteins; Structural Homology, Protein},
    month = {May},
    number = {2},
    pages = {255-61},
    pmid = {17285632},
    pst = {ppublish},
    title = {Analycys: a database for conservation and conformation of disulphide bonds in homologous protein domains},
    volume = {67},
    year = {2007},
    Bdsk-Url-1 = {https://doi.org/10.1002/prot.21318}}

  • Offmann, B., Tyagi, M., & de Brevern, A. G.. (2007). Local protein structures. Current bioinformatics, 2(3), 165–202.
    [BibTeX]
    @article{offmann2007local,
    author = {Offmann, Bernard and Tyagi, Manoj and de Brevern, Akexandre G},
    journal = {Current Bioinformatics},
    number = {3},
    pages = {165--202},
    publisher = {Bentham Science Publishers},
    title = {Local protein structures},
    volume = {2},
    year = {2007}}

  • Bornot, A., Offmann, B., & De Brevern, A.. (2007). How flexible protein structures are? new questions on the protein structure plasticity.. Bioforum europe(11), 24.
    [BibTeX]
    @article{bornot2007flexible,
    author = {Bornot, Aur{\'e}lie and Offmann, Bernard and De Brevern, Alexandre},
    journal = {Bioforum Europe},
    number = {11},
    pages = {24},
    title = {How flexible protein structures are? New questions on the protein structure plasticity.},
    year = {2007}}

  • Swapna, L., Offmann, B., & Srinivasan, N.. (2007). Evolutionary dynamics of protein-protein interactions. a case study using the dj-1/pfpi family of enzyme.. Knowledge discovery in bioinformatics: techniques, methods, and applications, 209–231.
    [BibTeX]
    @article{swapna2007evolutionary,
    author = {Swapna, LS and Offmann, B and Srinivasan, N},
    date-modified = {2020-02-23 21:11:28 +0100},
    journal = {Knowledge Discovery in Bioinformatics: Techniques, Methods, and Applications},
    pages = {209--231},
    publisher = {John Wiley \& Sons, Inc.},
    title = {Evolutionary dynamics of protein-protein interactions. A case study using the DJ-1/PfpI family of enzyme.},
    year = {2007}}

  • Chilamakuri, S. R. C., Khader, S., Offmann, B., & Sowdhamini, R.. (2007). Pure: a web server for querying the relationship between pre-existing domains and unassigned regions in proteins. Nature protocols(doi:10.1038/nprot.2007.486).
    [BibTeX]
    @article{chilamakuri2007pure,
    author = {Chilamakuri, C Sekhar Reddy and Khader, Shameer and Offmann, Bernard and Sowdhamini, Ramanathan},
    journal = {Nature Protocols},
    number = {doi:10.1038/nprot.2007.486},
    publisher = {Nature Publishing Group},
    title = {PURE: a web server for querying the relationship between pre-existing domains and unassigned regions in proteins},
    year = {2007}}

2006

  • Gardebien, F., Thangudu, R. R., Gontero, B., & Offmann, B.. (2006). Construction of a 3d model of cp12, a protein linker. J mol graph model, 25(2), 186-95. doi:10.1016/j.jmgm.2005.12.003
    [BibTeX] [Abstract]

    The chloroplast protein CP12 is known to play a leading role in a complex formation with the enzymes GAPDH and PRK. As a preliminary step towards the understanding of the complex formation mechanism and the exact role of this protein linker, a comparative modelling of the CP12 protein of the green alga Chlamydomonas reinhardtii was performed. Because of the very few structural information and poor template similarities, the derivation of the model consisted in an iterative trial-and-error procedure using the comparative modelling program MODELLER, the following three structure validation programs PROCHECK, PROSA, and WHATIF, and molecular mechanics energy refinement of the model using the program CHARMM. The analysis of the final model reveals a scaffold of key residues that is believed to be essential in the folding mechanism and that coincides with the residues conserved throughout the CP12 family. Our results suggest that this protein is a typical disordered protein. Finally, the various mechanisms by which the CP12 protein can self-interact or binds to other enzymes are discussed in light of its modelled structure and characteristics.

    @article{Gardebien:2006aa,
    abstract = {The chloroplast protein CP12 is known to play a leading role in a complex formation with the enzymes GAPDH and PRK. As a preliminary step towards the understanding of the complex formation mechanism and the exact role of this protein linker, a comparative modelling of the CP12 protein of the green alga Chlamydomonas reinhardtii was performed. Because of the very few structural information and poor template similarities, the derivation of the model consisted in an iterative trial-and-error procedure using the comparative modelling program MODELLER, the following three structure validation programs PROCHECK, PROSA, and WHATIF, and molecular mechanics energy refinement of the model using the program CHARMM. The analysis of the final model reveals a scaffold of key residues that is believed to be essential in the folding mechanism and that coincides with the residues conserved throughout the CP12 family. Our results suggest that this protein is a typical disordered protein. Finally, the various mechanisms by which the CP12 protein can self-interact or binds to other enzymes are discussed in light of its modelled structure and characteristics.},
    author = {Gardebien, Fabrice and Thangudu, Rajesh R and Gontero, Brigitte and Offmann, Bernard},
    date-added = {2019-10-12 00:56:09 +0200},
    date-modified = {2019-10-12 00:56:09 +0200},
    doi = {10.1016/j.jmgm.2005.12.003},
    journal = {J Mol Graph Model},
    journal-full = {Journal of molecular graphics \& modelling},
    mesh = {Algal Proteins; Amino Acid Sequence; Animals; Chlamydomonas reinhardtii; Chloroplasts; Computer Simulation; Glyceraldehyde-3-Phosphate Dehydrogenases; Models, Molecular; Molecular Sequence Data; Protein Binding; Protein Conformation; Protein Structure, Secondary; Sequence Homology, Amino Acid},
    month = {Oct},
    number = {2},
    pages = {186-95},
    pmid = {16427344},
    pst = {ppublish},
    title = {Construction of a 3D model of CP12, a protein linker},
    volume = {25},
    year = {2006},
    Bdsk-Url-1 = {https://doi.org/10.1016/j.jmgm.2005.12.003}}

  • Tyagi, M., Gowri, V. S., Srinivasan, N., de Brevern, A. G., & Offmann, B.. (2006). A substitution matrix for structural alphabet based on structural alignment of homologous proteins and its applications. Proteins, 65(1), 32-9. doi:10.1002/prot.21087
    [BibTeX] [Abstract]

    Analysis of protein structures based on backbone structural patterns known as structural alphabets have been shown to be very useful. Among them, a set of 16 pentapeptide structural motifs known as protein blocks (PBs) has been identified and upon which backbone model of most protein structures can be built. PBs allows simplification of 3D space onto 1D space in the form of sequence of PBs. Here, for the first time, substitution probabilities of PBs in a large number of aligned homologous protein structures have been studied and are expressed as a simplified 16 x 16 substitution matrix. The matrix was validated by benchmarking how well it can align sequences of PBs rather like amino acid alignment to identify structurally equivalent regions in closely or distantly related proteins using dynamic programming approach. The alignment results obtained are very comparable to well established structure comparison methods like DALI and STAMP. Other interesting applications of the matrix have been investigated. We first show that, in variable regions between two superimposed homologous proteins, one can distinguish between local conformational differences and rigid-body displacement of a conserved motif by comparing the PBs and their substitution scores. Second, we demonstrate, with the example of aspartic proteinases, that PBs can be efficiently used to detect the lobe/domain flexibility in the multidomain proteins. Lastly, using protein kinase as an example, we identify regions of conformational variations and rigid body movements in the enzyme as it is changed to the active state from an inactive state.

    @article{Tyagi:2006aa,
    abstract = {Analysis of protein structures based on backbone structural patterns known as structural alphabets have been shown to be very useful. Among them, a set of 16 pentapeptide structural motifs known as protein blocks (PBs) has been identified and upon which backbone model of most protein structures can be built. PBs allows simplification of 3D space onto 1D space in the form of sequence of PBs. Here, for the first time, substitution probabilities of PBs in a large number of aligned homologous protein structures have been studied and are expressed as a simplified 16 x 16 substitution matrix. The matrix was validated by benchmarking how well it can align sequences of PBs rather like amino acid alignment to identify structurally equivalent regions in closely or distantly related proteins using dynamic programming approach. The alignment results obtained are very comparable to well established structure comparison methods like DALI and STAMP. Other interesting applications of the matrix have been investigated. We first show that, in variable regions between two superimposed homologous proteins, one can distinguish between local conformational differences and rigid-body displacement of a conserved motif by comparing the PBs and their substitution scores. Second, we demonstrate, with the example of aspartic proteinases, that PBs can be efficiently used to detect the lobe/domain flexibility in the multidomain proteins. Lastly, using protein kinase as an example, we identify regions of conformational variations and rigid body movements in the enzyme as it is changed to the active state from an inactive state.},
    author = {Tyagi, Manoj and Gowri, Venkataraman S and Srinivasan, Narayanaswamy and de Brevern, Alexandre G and Offmann, Bernard},
    date-added = {2019-10-12 00:56:07 +0200},
    date-modified = {2019-10-12 00:56:07 +0200},
    doi = {10.1002/prot.21087},
    journal = {Proteins},
    journal-full = {Proteins},
    mesh = {Databases, Protein; Protein Conformation; Protein Folding; Sequence Alignment; Sequence Analysis, Protein},
    month = {Oct},
    number = {1},
    pages = {32-9},
    pmid = {16894618},
    pst = {ppublish},
    title = {A substitution matrix for structural alphabet based on structural alignment of homologous proteins and its applications},
    volume = {65},
    year = {2006},
    Bdsk-Url-1 = {https://doi.org/10.1002/prot.21087}}

  • Tyagi, M., Sharma, P., Swamy, C. S., Cadet, F., Srinivasan, N., de Brevern, A. G., & Offmann, B.. (2006). Protein block expert (pbe): a web-based protein structure analysis server using a structural alphabet. Nucleic acids res, 34(Web Server issue), W119-23. doi:10.1093/nar/gkl199
    [BibTeX] [Abstract]

    Encoding protein 3D structures into 1D string using short structural prototypes or structural alphabets opens a new front for structure comparison and analysis. Using the well-documented 16 motifs of Protein Blocks (PBs) as structural alphabet, we have developed a methodology to compare protein structures that are encoded as sequences of PBs by aligning them using dynamic programming which uses a substitution matrix for PBs. This methodology is implemented in the applications available in Protein Block Expert (PBE) server. PBE addresses common issues in the field of protein structure analysis such as comparison of proteins structures and identification of protein structures in structural databanks that resemble a given structure. PBE-T provides facility to transform any PDB file into sequences of PBs. PBE-ALIGNc performs comparison of two protein structures based on the alignment of their corresponding PB sequences. PBE-ALIGNm is a facility for mining SCOP database for similar structures based on the alignment of PBs. Besides, PBE provides an interface to a database (PBE-SAdb) of preprocessed PB sequences from SCOP culled at 95% and of all-against-all pairwise PB alignments at family and superfamily levels. PBE server is freely available at http://bioinformatics.univ-reunion.fr/PBE/.

    @article{Tyagi:2006ab,
    abstract = {Encoding protein 3D structures into 1D string using short structural prototypes or structural alphabets opens a new front for structure comparison and analysis. Using the well-documented 16 motifs of Protein Blocks (PBs) as structural alphabet, we have developed a methodology to compare protein structures that are encoded as sequences of PBs by aligning them using dynamic programming which uses a substitution matrix for PBs. This methodology is implemented in the applications available in Protein Block Expert (PBE) server. PBE addresses common issues in the field of protein structure analysis such as comparison of proteins structures and identification of protein structures in structural databanks that resemble a given structure. PBE-T provides facility to transform any PDB file into sequences of PBs. PBE-ALIGNc performs comparison of two protein structures based on the alignment of their corresponding PB sequences. PBE-ALIGNm is a facility for mining SCOP database for similar structures based on the alignment of PBs. Besides, PBE provides an interface to a database (PBE-SAdb) of preprocessed PB sequences from SCOP culled at 95% and of all-against-all pairwise PB alignments at family and superfamily levels. PBE server is freely available at http://bioinformatics.univ-reunion.fr/PBE/.},
    author = {Tyagi, M and Sharma, P and Swamy, C S and Cadet, F and Srinivasan, N and de Brevern, A G and Offmann, B},
    date-added = {2019-10-12 00:56:08 +0200},
    date-modified = {2019-10-12 00:56:08 +0200},
    doi = {10.1093/nar/gkl199},
    journal = {Nucleic Acids Res},
    journal-full = {Nucleic acids research},
    mesh = {Amino Acid Motifs; Databases, Protein; Internet; Protein Conformation; Protein Folding; Sequence Alignment; Sequence Analysis, Protein; Software; User-Computer Interface},
    month = {Jul},
    number = {Web Server issue},
    pages = {W119-23},
    pmc = {PMC1538797},
    pmid = {16844973},
    pst = {ppublish},
    title = {Protein Block Expert (PBE): a web-based protein structure analysis server using a structural alphabet},
    volume = {34},
    year = {2006},
    Bdsk-Url-1 = {https://doi.org/10.1093/nar/gkl199}}

2005

  • Thangudu, R. R., Vinayagam, A., Pugalenthi, G., Manonmani, A., Offmann, B., & Sowdhamini, R.. (2005). Native and modeled disulfide bonds in proteins: knowledge-based approaches toward structure prediction of disulfide-rich polypeptides. Proteins, 58(4), 866-79. doi:10.1002/prot.20369
    [BibTeX] [Abstract]

    Structure prediction and three-dimensional modeling of disulfide-rich systems are challenging due to the limited number of such folds in the structural databank. We exploit the stereochemical compatibility of substructures in known protein structures to accommodate disulfide bonds in predicting the structures of disulfide-rich polypeptides directly from disulfide connectivity pattern and amino acid sequence in the absence of structural homologs and any other structural information. This knowledge-based approach is illustrated using structure prediction of 40 nonredundant bioactive disulfide-rich polypeptides such as toxins, growth factors, and endothelins available in the structural databank. The polypeptide conformation could be predicted in 35 out of 40 nonredundant entries (87%). Nonhomologous templates could be identified and models could be obtained within 2 A deviation from the query in 29 peptides (72%). This procedure can be accessed from the World Wide Web (http://www.ncbs.res.in/ approximately faculty/mini/dsdbase/dsdbase.html).

    @article{Thangudu:2005aa,
    abstract = {Structure prediction and three-dimensional modeling of disulfide-rich systems are challenging due to the limited number of such folds in the structural databank. We exploit the stereochemical compatibility of substructures in known protein structures to accommodate disulfide bonds in predicting the structures of disulfide-rich polypeptides directly from disulfide connectivity pattern and amino acid sequence in the absence of structural homologs and any other structural information. This knowledge-based approach is illustrated using structure prediction of 40 nonredundant bioactive disulfide-rich polypeptides such as toxins, growth factors, and endothelins available in the structural databank. The polypeptide conformation could be predicted in 35 out of 40 nonredundant entries (87%). Nonhomologous templates could be identified and models could be obtained within 2 A deviation from the query in 29 peptides (72%). This procedure can be accessed from the World Wide Web (http://www.ncbs.res.in/ approximately faculty/mini/dsdbase/dsdbase.html).},
    author = {Thangudu, Ratna Rajesh and Vinayagam, A and Pugalenthi, G and Manonmani, A and Offmann, B and Sowdhamini, R},
    date-added = {2019-10-12 00:56:10 +0200},
    date-modified = {2019-10-12 00:56:10 +0200},
    doi = {10.1002/prot.20369},
    journal = {Proteins},
    journal-full = {Proteins},
    mesh = {Algorithms; Amino Acid Sequence; Amino Acids; Animals; Artificial Intelligence; Computational Biology; Computer Simulation; Databases, Protein; Disulfides; Growth Substances; Humans; Internet; Magnetic Resonance Spectroscopy; Models, Biological; Models, Molecular; Molecular Conformation; Peptides; Protein Conformation; Protein Folding; Protein Structure, Tertiary; Proteomics; Sequence Analysis, Protein; Software; Stereoisomerism},
    month = {Mar},
    number = {4},
    pages = {866-79},
    pmid = {15645448},
    pst = {ppublish},
    title = {Native and modeled disulfide bonds in proteins: knowledge-based approaches toward structure prediction of disulfide-rich polypeptides},
    volume = {58},
    year = {2005},
    Bdsk-Url-1 = {https://doi.org/10.1002/prot.20369}}

2003

  • Besnard, G., Pinçon, G., D’Hont, A., Hoarau, J-Y., Cadet, F., & Offmann, B.. (2003). Characterisation of the phosphoenolpyruvate carboxylase gene family in sugarcane (saccharum spp.). Theor appl genet, 107(3), 470-8. doi:10.1007/s00122-003-1268-2
    [BibTeX] [Abstract]

    Phosphoenolpyruvate carboxylases (PEPCs) are encoded by a small multigenic family. In order to characterise this gene family in sugarcane, seven DNA fragments displaying a high homology with grass PEPC genes were isolated using polymerase chain reaction-based cloning. A phylogenetic study revealed the existence of four main PEPC gene lineages in grasses and particularly in sugarcane. Moreover, this analysis suggests that grass C4 PEPC has likely derived from a root pre-existing isoform in an ancestral species. Using the Northern-dot-blot method, we studied the expression of the four PEPC gene classes in sugarcane cv. R570. We confirmed that transcript accumulation of the C4 PEPC gene (ppc-C4) mainly occurs in the green leaves and is light-induced. We also showed that another member of this gene family (ppc-aR) is more highly transcribed in the roots. The constitutive expression for a previously characterised gene (ppc-aL2) was confirmed. Lastly, the transcript accumulation of the fourth PEPC gene class (ppc-aL1) was not revealed. Length polymorphism in non-coding regions for three PEPC gene lineages enabled us to develop sequence-tagged site PEPC markers in sugarcane. We analysed the segregation of PEPC fragments in self-pollinated progenies of cv. R570 and found co-segregating fragments for two PEPC gene lineages. This supports the hypothesis that diversification of the PEPC genes involved duplications, probably in tandem.

    @article{Besnard:2003aa,
    abstract = {Phosphoenolpyruvate carboxylases (PEPCs) are encoded by a small multigenic family. In order to characterise this gene family in sugarcane, seven DNA fragments displaying a high homology with grass PEPC genes were isolated using polymerase chain reaction-based cloning. A phylogenetic study revealed the existence of four main PEPC gene lineages in grasses and particularly in sugarcane. Moreover, this analysis suggests that grass C4 PEPC has likely derived from a root pre-existing isoform in an ancestral species. Using the Northern-dot-blot method, we studied the expression of the four PEPC gene classes in sugarcane cv. R570. We confirmed that transcript accumulation of the C4 PEPC gene (ppc-C4) mainly occurs in the green leaves and is light-induced. We also showed that another member of this gene family (ppc-aR) is more highly transcribed in the roots. The constitutive expression for a previously characterised gene (ppc-aL2) was confirmed. Lastly, the transcript accumulation of the fourth PEPC gene class (ppc-aL1) was not revealed. Length polymorphism in non-coding regions for three PEPC gene lineages enabled us to develop sequence-tagged site PEPC markers in sugarcane. We analysed the segregation of PEPC fragments in self-pollinated progenies of cv. R570 and found co-segregating fragments for two PEPC gene lineages. This supports the hypothesis that diversification of the PEPC genes involved duplications, probably in tandem.},
    author = {Besnard, G and Pin{\c c}on, G and D'Hont, A and Hoarau, J-Y and Cadet, F and Offmann, B},
    date-added = {2019-10-12 00:56:11 +0200},
    date-modified = {2019-10-12 00:56:11 +0200},
    doi = {10.1007/s00122-003-1268-2},
    journal = {Theor Appl Genet},
    journal-full = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik},
    mesh = {Base Sequence; Blotting, Northern; Cluster Analysis; DNA Primers; Molecular Sequence Data; Multigene Family; Organ Specificity; Phosphoenolpyruvate Carboxylase; Phylogeny; Polymorphism, Restriction Fragment Length; Reverse Transcriptase Polymerase Chain Reaction; Saccharum; Sequence Alignment; Sequence Analysis, DNA},
    month = {Aug},
    number = {3},
    pages = {470-8},
    pmid = {12759729},
    pst = {ppublish},
    title = {Characterisation of the phosphoenolpyruvate carboxylase gene family in sugarcane (Saccharum spp.)},
    volume = {107},
    year = {2003},
    Bdsk-Url-1 = {https://doi.org/10.1007/s00122-003-1268-2}}

  • OFFMANN, B., RABOIN, L. M., & NOTAISE, J.. (2003). Segregation of resistance to xanthomonas albilineans in a sugarcane progeny. The journal of nature, 15(1), 113–124.
    [BibTeX]
    @article{offmann2003segregation,
    author = {OFFMANN, Bernard and RABOIN, Louis Marie and NOTAISE, Julien},
    journal = {The Journal of nature},
    number = {1},
    pages = {113--124},
    publisher = {Bourbon sciences},
    title = {Segregation of resistance to Xanthomonas albilineans in a sugarcane progeny},
    volume = {15},
    year = {2003}}

2002

  • Hoarau, J. -Y., Grivet, L., Offmann, B., Raboin, L. -M., Diorflar, J. -P., Payet, J., Hellmann, M., D’Hont, A., & Glaszmann, J. -C.. (2002). Genetic dissection of a modern sugarcane cultivar ( saccharum spp.).ii. detection of qtls for yield components. Theor appl genet, 105(6-7), 1027-1037. doi:10.1007/s00122-002-1047-5
    [BibTeX] [Abstract]

    The genetics of current sugarcane cultivars ( Saccharum spp.) is outstandingly complex, due to a high ploidy level and an interspecific origin which leads to the presence of numerous chromosomes belonging to two ancestral genomes. In order to analyse the inheritance of quantitative traits, we have undertaken an extensive Quantitative Trait Allele (QTA) mapping study based on a population of 295 progenies derived from the selfing of cultivar R570, using about 1,000 AFLP markers scattered on about half of the genome. The population was evaluated in a replicated trial for four basic yield components, plant height, stalk number, stalk diameter and brix, in two successive crop-cycles. Forty putative QTAs were found for the four traits at P = 5 x 10(-3), of which five appeared in both years. Their individual size ranged between 3 and 7% of the whole variation. The stability across years was improved when limiting threshold stringency. All these results depict the presence in the genome of numerous QTAs, with little effects, fluctuating slightly across cycles, on the verge to being perceptible given the experimental resolution. Epistatic interactions were also explored and 41 independent di-genic interactions were found at P = (5 x 10(-3))(2). Altogether the putative genetic factors revealed here explain from 30 to 55% of the total phenotypic variance depending on the trait. The tentative assignment of some QTAs to the ancestral genomes showed a small majority of contributions as expected from the ancestral phenotypes. This is the first extensive QTL mapping study performed in cultivated sugarcane.

    @article{Hoarau:2002aa,
    abstract = {The genetics of current sugarcane cultivars ( Saccharum spp.) is outstandingly complex, due to a high ploidy level and an interspecific origin which leads to the presence of numerous chromosomes belonging to two ancestral genomes. In order to analyse the inheritance of quantitative traits, we have undertaken an extensive Quantitative Trait Allele (QTA) mapping study based on a population of 295 progenies derived from the selfing of cultivar R570, using about 1,000 AFLP markers scattered on about half of the genome. The population was evaluated in a replicated trial for four basic yield components, plant height, stalk number, stalk diameter and brix, in two successive crop-cycles. Forty putative QTAs were found for the four traits at P = 5 x 10(-3), of which five appeared in both years. Their individual size ranged between 3 and 7% of the whole variation. The stability across years was improved when limiting threshold stringency. All these results depict the presence in the genome of numerous QTAs, with little effects, fluctuating slightly across cycles, on the verge to being perceptible given the experimental resolution. Epistatic interactions were also explored and 41 independent di-genic interactions were found at P = (5 x 10(-3))(2). Altogether the putative genetic factors revealed here explain from 30 to 55% of the total phenotypic variance depending on the trait. The tentative assignment of some QTAs to the ancestral genomes showed a small majority of contributions as expected from the ancestral phenotypes. This is the first extensive QTL mapping study performed in cultivated sugarcane.},
    author = {Hoarau, J.-Y. and Grivet, L. and Offmann, B. and Raboin, L.-M. and Diorflar, J.-P. and Payet, J. and Hellmann, M. and D'Hont, A. and Glaszmann, J.-C.},
    date-added = {2019-10-12 00:56:12 +0200},
    date-modified = {2019-10-12 00:56:12 +0200},
    doi = {10.1007/s00122-002-1047-5},
    journal = {Theor Appl Genet},
    journal-full = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik},
    month = {Nov},
    number = {6-7},
    pages = {1027-1037},
    pmid = {12582930},
    pst = {ppublish},
    title = {Genetic dissection of a modern sugarcane cultivar ( Saccharum spp.).II. Detection of QTLs for yield components},
    volume = {105},
    year = {2002},
    Bdsk-Url-1 = {https://doi.org/10.1007/s00122-002-1047-5}}

  • Besnard, G., Offmann, B., Robert, C., Rouch, C., & Cadet, F.. (2002). Assessment of the c(4) phosphoenolpyruvate carboxylase gene diversity in grasses (poaceae). Theor appl genet, 105(2-3), 404-412. doi:10.1007/s00122-001-0851-7
    [BibTeX] [Abstract]

    C(4) phosphoenolpyruvate carboxylase (PEPC) is a key enzyme in the C(4) photosynthetic pathway. To analyze the diversity of the corresponding gene in grasses, we designed PCR primers to specifically amplify C(4) PEPC cDNA fragments. Using RT-PCR, we generated partial PEPC cDNA sequences in several grasses displaying a C(4) photosynthetic pathway. All these sequences displayed a high homology (78-99%) with known grass C(4) PEPCs. PCR amplification did not occur in two grasses that display the C(3) photosynthetic pathway, and therefore we assumed that all generated sequences corresponded to C(4) PEPC transcripts. Based on one large cDNA segment, phylogenetic reconstruction enabled us to assess the relationships between 22 grass species belonging to the subfamilies Panicoideae, Arundinoideae and Chloridoideae. The phylogenetic relationships between species deduced from C(4) PEPC sequences were similar to those deduced from other molecular data. The sequence evolution of the C(4) PEPC isoform was faster than in the other PEPC isoforms. Finally, the utility of the C(4) PEPC gene phylogeny to study the evolution of C(4) photosynthesis in grasses is discussed.

    @article{Besnard:2002aa,
    abstract = {C(4) phosphoenolpyruvate carboxylase (PEPC) is a key enzyme in the C(4) photosynthetic pathway. To analyze the diversity of the corresponding gene in grasses, we designed PCR primers to specifically amplify C(4) PEPC cDNA fragments. Using RT-PCR, we generated partial PEPC cDNA sequences in several grasses displaying a C(4) photosynthetic pathway. All these sequences displayed a high homology (78-99%) with known grass C(4) PEPCs. PCR amplification did not occur in two grasses that display the C(3) photosynthetic pathway, and therefore we assumed that all generated sequences corresponded to C(4) PEPC transcripts. Based on one large cDNA segment, phylogenetic reconstruction enabled us to assess the relationships between 22 grass species belonging to the subfamilies Panicoideae, Arundinoideae and Chloridoideae. The phylogenetic relationships between species deduced from C(4) PEPC sequences were similar to those deduced from other molecular data. The sequence evolution of the C(4) PEPC isoform was faster than in the other PEPC isoforms. Finally, the utility of the C(4) PEPC gene phylogeny to study the evolution of C(4) photosynthesis in grasses is discussed.},
    author = {Besnard, G. and Offmann, B. and Robert, C. and Rouch, C. and Cadet, F.},
    date-added = {2019-10-12 00:56:13 +0200},
    date-modified = {2019-10-12 00:56:13 +0200},
    doi = {10.1007/s00122-001-0851-7},
    journal = {Theor Appl Genet},
    journal-full = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik},
    month = {Aug},
    number = {2-3},
    pages = {404-412},
    pmid = {12582545},
    pst = {ppublish},
    title = {Assessment of the C(4) phosphoenolpyruvate carboxylase gene diversity in grasses (Poaceae)},
    volume = {105},
    year = {2002},
    Bdsk-Url-1 = {https://doi.org/10.1007/s00122-001-0851-7}}

  • Offmann, B., & Cadet, F.. (2002). Enzymes as structural tool in infrared spectroscopy. Spectroscopy letters, 35(4), 523–526.
    [BibTeX]
    @article{offmann2002enzymes,
    author = {Offmann, Bernard and Cadet, Fr{\'e}d{\'e}ric},
    journal = {Spectroscopy letters},
    number = {4},
    pages = {523--526},
    publisher = {Taylor \& Francis},
    title = {Enzymes as structural tool in infrared spectroscopy},
    volume = {35},
    year = {2002}}

  • Offmann, B., & Cadet, F.. (2002). Redox-active disulfides in a plant light switch: a pbl problem. Biochemistry and molecular biology education, 30(4), 249–254.
    [BibTeX]
    @article{offmann2002redox,
    author = {Offmann, Bernard and Cadet, Fr{\'e}d{\'e}ric},
    journal = {Biochemistry and Molecular Biology Education},
    number = {4},
    pages = {249--254},
    publisher = {John Wiley \& Sons Inc. USA},
    title = {Redox-active disulfides in a plant light switch: A Pbl problem},
    volume = {30},
    year = {2002}}

2001

  • Hoarau, J-Y., Offmann, B., D’Hont, A., Risterucci, A-M., Roques, D., Glaszmann, J-C., & Grivet, L.. (2001). Genetic dissection of a modern sugarcane cultivar (saccharum spp.). i. genome mapping with aflp markers. Theoretical and applied genetics, 103(1), 84–97.
    [BibTeX]
    @article{hoarau2001genetic,
    author = {Hoarau, J-Y and Offmann, B and D'Hont, Ang{\'e}lique and Risterucci, A-M and Roques, D and Glaszmann, J-C and Grivet, Laurent},
    journal = {Theoretical and Applied Genetics},
    number = {1},
    pages = {84--97},
    publisher = {Springer-Verlag},
    title = {Genetic dissection of a modern sugarcane cultivar (Saccharum spp.). I. Genome mapping with AFLP markers},
    volume = {103},
    year = {2001}}

  • Raboin, L., Offmann, B., Hoarau, J., Notaise, J., Costet, L., Telismart, H., Roques, D., Rott, P., Glaszmann, J., & D’Hont, A.. (2001). Undertaking genetic mapping of sugarcane smut resistance. Paper presented at the Proc s afr sug technol ass.
    [BibTeX] [Abstract]

    Smut is one of the most important diseases of sugarcane and has a worldwide distribution. It can cause severe yield losses when a susceptible variety is grown in a smut infested area. Resistance is therefore a major concern for most sugarcane breeding centers. A study on the genetic determinism underlying sugarcane smut resistance was initiated. A genetic mapping strategy was cho- sen that focused on a cross between cultivar R 570 (resistant) and cultivar MQ 76/53 (highly susceptible) which showed a segregation for smut resistance in a preliminary field trial. An AFLP map is being constructed for both parents of the cross. At the same time, field trials and greenhouse experiments have begun using different artificial inoculation methods to assess the resistance of 200 individual progeny.This paper presents first results on smut occurrence among this progeny and correlations between segregating markers and re- sistance to smut. Other characters have also been observed (Brix, number of stalks, rust resistance). The possibility of iden- tifying the different components involved in smut resistance and the interest of locus specific markers (SSR, resistance gene analogs, etc) to refine the genetic map are discussed.

    @inproceedings{raboin2001undertaking,
    abstract = {Smut is one of the most important diseases of sugarcane and has a worldwide distribution. It can cause severe yield losses when a susceptible variety is grown in a smut infested area. Resistance is therefore a major concern for most sugarcane breeding centers. A study on the genetic determinism underlying sugarcane smut resistance was initiated. A genetic mapping strategy was cho- sen that focused on a cross between cultivar R 570 (resistant) and cultivar MQ 76/53 (highly susceptible) which showed a segregation for smut resistance in a preliminary field trial. An AFLP map is being constructed for both parents of the cross. At the same time, field trials and greenhouse experiments have begun using different artificial inoculation methods to assess the resistance of 200 individual progeny.This paper presents first results on smut occurrence among this progeny and correlations between segregating markers and re- sistance to smut. Other characters have also been observed (Brix, number of stalks, rust resistance). The possibility of iden- tifying the different components involved in smut resistance and the interest of locus specific markers (SSR, resistance gene analogs, etc) to refine the genetic map are discussed.},
    author = {Raboin, Louis-Marie and Offmann, B and Hoarau, Jean-Yves and Notaise, Julien and Costet, Laurent and Telismart, Hugues and Roques, Dani{\`e}le and Rott, Philippe and Glaszmann, Jean-Christophe and D'Hont, Ang{\'e}lique},
    booktitle = {Proc S Afr Sug Technol Ass},
    pages = {94--98},
    title = {Undertaking genetic mapping of sugarcane smut resistance},
    volume = {75},
    year = {2001}}

  • Besnard, G., Offman, B., Robert, C., Baret, P., Rouch, C., & Cadet, F.. (2001). Phosphoenolpyruvate carboxylase cdna phylogeny to investigate the c4 photosynthetic pathway evolution in grasses. Science access, 3(1).
    [BibTeX]
    @article{besnard2001phosphoenolpyruvate,
    author = {Besnard, Guillaume and Offman, Bernard and Robert, Christine and Baret, Pascal and Rouch, Claude and Cadet, Fr{\'e}d{\'e}ric},
    journal = {Science Access},
    number = {1},
    publisher = {CSIRO},
    title = {Phosphoenolpyruvate carboxylase cDNA phylogeny to investigate the C4 photosynthetic pathway evolution in grasses},
    volume = {3},
    year = {2001}}

2000

  • Offmann, B.. ((2000). Caractérisation et analyse génétique de la résistance de la canne à sucre à xanthomonas albilineans.). PhD Thesis.
    [BibTeX]
    @phdthesis{offmann2000caracterisation,
    author = {Offmann, Bernard},
    date-added = {2020-02-23 21:16:44 +0100},
    date-modified = {2020-02-23 21:16:44 +0100},
    school = {La R{\'e}union},
    title = {Caract{\'e}risation et analyse g{\'e}n{\'e}tique de la r{\'e}sistance de la canne {\`a} sucre {\`a} Xanthomonas albilineans},
    year = {2000}}

1997

  • Offmann, B. G.. ((1997). Cartographie génétique et recherche de qtls chez un cultivar élite de canne à sucre (\# saccharum\# spp) au moyen de marqueurs aflp.). Master Thesis.
    [BibTeX]
    @mastersthesis{offmann1997cartographie,
    author = {Offmann, Bernard Gilles},
    date-added = {2020-02-23 21:16:30 +0100},
    date-modified = {2020-02-23 21:16:30 +0100},
    month = {July},
    school = {Universit{\'e} de Paris VII},
    title = {Cartographie g{\'e}n{\'e}tique et recherche de QTLs chez un cultivar {\'e}lite de canne {\`a} sucre (\# Saccharum\# spp) au moyen de marqueurs AFLP},
    year = {1997}}

  • Cadet, F., & Offmann, B.. (1997). Direct spectroscopic sucrose determination of raw sugar cane juices. Journal of agricultural and food chemistry, 45(1), 166–171.
    [BibTeX]
    @article{cadet1997direct,
    author = {Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard},
    journal = {Journal of Agricultural and Food Chemistry},
    number = {1},
    pages = {166--171},
    publisher = {American Chemical Society},
    title = {Direct spectroscopic sucrose determination of raw sugar cane juices},
    volume = {45},
    year = {1997}}

  • Cadet, F., Robert, C., & Offmann, B.. (1997). Simultaneous determination of sugars by multivariate analysis applied to mid-infrared spectra of biological samples. Applied spectroscopy, 51(3), 369–375.
    [BibTeX]
    @article{cadet1997simultaneous,
    author = {Cadet, Fr{\'e}d{\'e}ric and Robert, Christine and Offmann, Bernard},
    journal = {Applied spectroscopy},
    number = {3},
    pages = {369--375},
    publisher = {Society for Applied Spectroscopy},
    title = {Simultaneous determination of sugars by multivariate analysis applied to mid-infrared spectra of biological samples},
    volume = {51},
    year = {1997}}

1996

  • CADET, F., & OFFMANN, B.. (1996). Extraction of characteristic bands of sugars by multidimensional analysis of their infrared spectra.. Spectroscopy letters, 29(3), 523–536.
    [BibTeX]
    @article{cadet1996extraction,
    author = {CADET, Fr{\'E}D{\'E}Ric and OFFMANN, Bernard},
    journal = {Spectroscopy letters},
    number = {3},
    pages = {523--536},
    publisher = {Taylor \& Francis},
    title = {Extraction of Characteristic Bands of Sugars by Multidimensional Analysis of Their Infrared Spectra.},
    volume = {29},
    year = {1996}}

  • Cadet, F., & Offmann, B.. (1996). Evidence for potassium-sucrose interaction in biological mid-infrared spectra by multidimensional analysis. Spectroscopy letters, 29(7), 1353–1365.
    [BibTeX]
    @article{cadet1996evidence,
    author = {Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard},
    journal = {Spectroscopy letters},
    number = {7},
    pages = {1353--1365},
    publisher = {Taylor \& Francis},
    title = {Evidence for Potassium-Sucrose Interaction in Biological Mid-Infrared Spectra by Multidimensional Analysis},
    volume = {29},
    year = {1996}}

  • Cadet, F., & Offmann, B.. (1996). Baseline correction applied to a biological: mid-infrared spectra collection. Spectroscopy letters, 29(4), 591–607.
    [BibTeX]
    @article{cadet1996baseline,
    author = {Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard},
    journal = {Spectroscopy letters},
    number = {4},
    pages = {591--607},
    publisher = {Taylor \& Francis Group},
    title = {Baseline correction applied to a biological: Mid-infrared spectra collection},
    volume = {29},
    year = {1996}}

  • Cadet, F., & Offmann, B.. (1996). Gram-schmidt orthogonalization and elimination of the effect of unwanted component spectra applied to a biological mid-infrared spectra collection. Spectroscopy letters, 29(5), 901–918.
    [BibTeX]
    @article{cadet1996gram,
    author = {Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard},
    journal = {Spectroscopy letters},
    number = {5},
    pages = {901--918},
    publisher = {Taylor \& Francis},
    title = {Gram-Schmidt Orthogonalization and Elimination of the Effect of Unwanted Component Spectra Applied to a Biological Mid-infrared Spectra Collection},
    volume = {29},
    year = {1996}}