Sofia Kossida | Centre National de la Recherche Scientifique / French National Centre for Scientific Research (original) (raw)

Papers by Sofia Kossida

The analysis of adaptive immune repertoires in autoimmune and infectious diseases represents a fa... more The analysis of adaptive immune repertoires in autoimmune and infectious diseases represents a fascinating challenge because of the natural huge diversity of the antigen receptors that are the immunoglobulins or antibodies and T cell receptors, expressed by B cells and T cells, respectively. The high throughput analysis resulting from the next generation sequencing technologies offers an invaluable large scale characterization of the expressed repertoires and, consequently, a better understanding of the protective and pathogenic immune responses. IMGT ® , the international ImMunoGeneTics information system ® (Centre National de la Recherche Scientifique and Montpellier University) is the global reference in immunogenetics and immunoinformatics. By its creation in 1989, IMGT ® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT ® is specialized in the immunoglobulins or antibodies, T cell receptors, major histocompatibility proteins of humans and other vertebrate species, and in the proteins of the immunoglobulin superfamily and major histocompatibility superfamily of any species. IMGT ® has been built on the IMGT-ONTOLOGY axioms and concepts, which bridged the gap between genes, sequences and three-dimensional structures. The concepts include the IMGT ® standardized keywords (identification), IMGT ® standardized labels (description), IMGT ® standardized nomenclature (classification), IMGT unique numbering and IMGT Colliers de Perles (numerotation). IMGT ® comprises seven databases, 15,000 pages of web resources and 17 tools, and includes data from fishes to humans, for basic to veterinary, medical and translational research. IMGT/HighV-QUEST, the high throughput version of IMGT/V-QUEST and IMGT/Junction Analysis, created in 2010, is the first and, so far, the only online portal for analysis of the immunoglobulin and T cell receptor repertoires obtained from next generation sequencing. High-quality results contribute to the large scale vision of antigen receptor repertoires and understanding of the adaptive immune responses (protective in vaccination, cancer and infections and pathogenic in autoimmunity) for diagnosis, prognosis and therapy.

Leukemia, May 25, 2022

The somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gen... more The somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene is a critical biomarker for assessing the prognosis of patients with chronic lymphocytic leukemia (CLL). Importantly, independent studies have documented that IGHV SHM status is also a predictor of responses to therapy, including both chemoimmunotherapy (CIT) and novel, targeted agents. Moreover, immunogenetic analysis in CLL has revealed that different patients may express (quasi)identical, stereotyped B cell receptor immunoglobulin (BcR IG) and are classified into subsets based on this common feature. Patients in certain stereotyped subsets display consistent biology, clinical presentation, and outcome that are distinct from other patients, even with concordant IGHV gene SHM status. All of the above highlights the relevance of immunogenetic analysis in CLL, which is considered a cornerstone for accurate risk stratification and clinical decision making. Recommendations for robust immunogenetic analysis exist thanks to dedicated efforts by ERIC, the European Research Initiative on CLL, covering all test phases, from the pre-analytical and analytical to the post-analytical, pertaining to the analysis, interpretation, and reporting of the findings. That said, these recommendations apply to Sanger sequencing, which is increasingly being superseded by next generation sequencing (NGS), further underscoring the need for an update. Here, we present an overview of the clinical utility of immunogenetics in CLL and update our analytical recommendations with the aim to assist in the refined management of patients with CLL.

Frontiers in Immunology

BackgroundCancer cells activate different immune checkpoint (IC) pathways in order to evade immun... more BackgroundCancer cells activate different immune checkpoint (IC) pathways in order to evade immunosurveillance. Immunotherapies involving ICs either block or stimulate these pathways and enhance the efficiency of the immune system to recognize and attack cancer cells. In this way, the development of monoclonal antibodies (mAbs) targeting ICs has significant success in cancer treatment. Recently, a systematic description of the mechanisms of action (MOA) of the mAbs has been introduced in IMGT/mAb-DB, the IMGT® database dedicated to mAbs for therapeutic applications. The characterization of these antibodies provides a comprehensive understanding of how mAbs work in cancer.MethodsIn depth biocuration taking advantage of the abundant literature data as well as amino acid sequence analyses from mAbs managed in IMGT/2Dstructure-DB, the IMGT® protein database, allowed to define a standardized and consistent description of the MOA of mAbs targeting immune checkpoints in cancer therapy.Resu...

Vaccines, Mar 3, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Methods in molecular biology, 2022

The variable domains (V-DOMAIN) of the antigen receptors, immunoglobulins (IG) or antibodies and ... more The variable domains (V-DOMAIN) of the antigen receptors, immunoglobulins (IG) or antibodies and T cell receptors (TR), which specifically recognize the antigens show a huge diversity in their sequences. This diversity results from the complex mechanisms involved in the synthesis of these domains at the DNA level (rearrangements of the variable (V), diversity (D), and joining (J) genes; N-diversity; and, for the IG, somatic hypermutations). The recognition of V, D, and J as "genes" and their entry in databases mark the creation of IMGT by Marie-Paule Lefranc, and the origin of immunoinformatics in 1989. For 30 years, IMGT ® , the international ImMunoGeneTics information system ® http://www.imgt.org, has implemented databases and developed tools for IG and TR immunoinformatics, based on the IMGT Scientific chart rules and IMGT-ONTOLOGY concepts and axioms, and more particularly, the princeps ones: IMGT genes and alleles (CLASSIFICATION axiom) and the IMGT unique numbering and IMGT Collier de Perles (NUMEROTATION axiom). This chapter describes the online tools for the characterization and annotation of the expressed V-DOMAIN sequences: (a) IMGT/V-QUEST analyzes in detail IG and TR rearranged nucleotide sequences, (b) IMGT/HighV-QUEST is its high throughput version, which includes a module for the identification of IMGT clonotypes and generates immunoprofiles of expressed V, D, and J genes and alleles, (c) IMGT/StatClonotype performs the pairwise comparison of IMGT/HighV-QUEST immunoprofiles, (d) IMGT/DomainGapAlign analyzes amino acid sequences and is frequently used in antibody engineering and humanization, and (e) IMGT/Collier-de-Perles provides two-dimensional (2D) graphical representations of V-DOMAIN, bridging the gap between sequences and 3D structures. These IMGT® tools are widely used in repertoire analyses of the adaptive immune responses in normal and pathological situations and in the design of engineered IG and TR for therapeutic applications.

Springer International Publishing eBooks, 2022

Herein we report the establishment of the 3D structure of the biglycan core protein, using conven... more Herein we report the establishment of the 3D structure of the biglycan core protein, using conventional homology molecular modelling techniques. The 3D model has been structurally optimised via molecular dynamics. It was found that the final model of biglycan resembles in structure its template protein bearing a set of distinct parallel β-sheet structure patterns. The biglycan model bears a very hydrophobic amino acid region towards its inner cavity that acquires an arc-like structure. The external domain of the biglycan model is made up of hydrophilic residues that are exposed to the water solvent. It is those hydrophilic residues that are responsible for their interaction with polysaccharide polymers. Overall comparison of the model of biglycan to the recently determined x-ray structure of the same protein returns a very low Root Mean Square Deviation (RMSD), which confirms the viability of the model and its reliability as a platform for the study biglycan interactions.

The b-ketoacyl carrier protein synthases (the KAS enzymes) are key enzymes that can be used as po... more The b-ketoacyl carrier protein synthases (the KAS enzymes) are key enzymes that can be used as potential anti-Plasmodium drug targets. In bacteria, three KAS enzymes have been identified (KAS I, KAS II and KAS III), whilst in Plasmodium a KAS I/II and KAS III enzyme has been reported. The protein has a total of four active sites, which have been found to be different to each other, rather than four copies of the same active site. The active sites differ not only in the type of interaction they establish with the ligand, but, in the case of Cerulenin as a ligand, the active sites of the KAS I/II enzyme also differ in the number of residues involved in the ligand protein interaction. This is very interesting biochemically, because these differences imply that the affinity of each active site for binding to the ligand might be different as well.

The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) ar... more The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) are characterized by the B and T cells and their specific antigen recep-tors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR) (up to 2.1012 dif-ferent IG and TR per individual). IMGT, the international ImMunoGeneTics information system (http://www.imgt.org), was created in 1989 by Marie-Paule Lefranc (Montpellier Uni-versity and CNRS) to manage the huge and complex diversity of these antigen receptors. IMGT built on IMGT-ONTOLOGY concepts of identification (keywords), description (labels), classification (gene and allele nomenclature) and numerotation (IMGT unique numbering), is at the origin of immunoinformatics, a science at the interface between immunogenetics and bioinformatics. IMGT/HighV-QUEST, the first web portal, and so far the only one, for the next generation sequencing (NGS) analysis of IG and TR, is the paradigm for immune repertoire standardized outputs a...

IMGT R©, the international ImMunoGeneTics informa-tion system R ©

Journal of molecular biochemistry

Herein, we present a novel strategy to analyse and characterize proteins using protein molecular ... more Herein, we present a novel strategy to analyse and characterize proteins using protein molecular electro-static surfaces. Our approach starts by calculating a series of distinct molecular surfaces for each protein that are subsequently flattened out, thus reducing 3D information noise. RGB images are appropriately scaled by means of standard image processing techniques whilst retaining the weight information of each protein's molecular electrostatic surface. Then homogeneous areas in the protein surface are estimated based on unsupervised clustering of the 3D images, while performing similarity searches. This is a computationally fast approach, which efficiently highlights interesting structural areas among a group of proteins. Multiple protein electrostatic surfaces can be combined together and in conjunction with their processed images, they can provide the starting material for protein structural similarity and molecular docking experiments.

Flaviviridae is a family of RNA viruses that includes numerous important human and animal pathoge... more Flaviviridae is a family of RNA viruses that includes numerous important human and animal pathogens. Recent studies on subgenomic flaviviridae replicons have revealed that the non-structural (NS) proteins, which are encoded by the C-terminal part of the polyprotein, play a crucial role in viral RNA replication. Accordingly, these proteins are assumed to form replication complexes in conjunction with genomic RNA and possibly with other cellular factors. One the most important non-structural enzymes that plays a key role in the life cycle of flaviviridae viruses is the viral helicase. Sequence alignments of the viral helicases from this family identified several conserved sequence motifs that are important for biological functions. Herein, an effort is made to summarize the current epidemics associated with the flaviviridae family worldwide, the potential of helicase enzymes as a promising pharmacological target and the use of nucleoside analogs as simple, efficient and rather versatile antiviral agents.

Methods in molecular biology (Clifton, N.J.), 2012

IMGT(®), the international ImMunoGeneTics information system(®) (http://www.imgt.org), was create... more IMGT(®), the international ImMunoGeneTics information system(®) (http://www.imgt.org), was created in 1989 to manage the huge diversity of the antigen receptors, immunoglobulins (IG) or antibodies, and T cell receptors (TR). Standardized sequence and structure analysis of antibody using IMGT(®) databases and tools allows one to bridge, for the first time, the gap between antibody sequences and three-dimensional (3D) structures. This is achieved through the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY concepts of classification (IMGT gene and allele nomenclature), description (IMGT standardized labels), and numerotation (IMGT unique numbering and IMGT Colliers de Perles). IMGT(®) is the international reference for immunogenetics and immunoinformatics and its standards are particularly useful for antibody humanization and evaluation of immunogenicity. IMGT(®) databases for antibody nucleotide sequences and genes include IMGT/LIGM-DB and IMGT/GENE-DB, respectively, whereas n...

Evolutionary Bioinformatics, 2013

The versatility of human immunodeficiency virus (HIV)-1 and its evolutionary potential to elude a... more The versatility of human immunodeficiency virus (HIV)-1 and its evolutionary potential to elude antiretroviral agents by mutating may be its most invincible weapon. Viruses, including HIV, in order to adapt and survive in their environment evolve at extremely fast rates. Given that conventional approaches which have been applied against HIV have failed, novel and more promising approaches must be employed. Recent studies advocate RNA interference (RNAi) as a promising therapeutic tool against HIV In this regard, targeting multiple HIV sites in the context of a combinatorial RNAi-based approach may efficiently stop viral propagation at an early stage. Moreover, large high-throughput RNAi screens are widely used in the fields of drug development and reverse genetics. Computer-based algorithms, bioinformatics, and biostatistical approaches have been employed in traditional medicinal chemistry discovery protocols for low molecular weight compounds. However, the diversity and complexity ...

Evolutionary Bioinformatics, 2013

Deadenylases catalyze the shortening of the poly(A) tail at the messenger ribonucleic acid (mRNA)... more Deadenylases catalyze the shortening of the poly(A) tail at the messenger ribonucleic acid (mRNA) 3′-end in eukaryotes. Therefore, these enzymes influence mRNA decay, and constitute a major emerging group of promising anti-cancer pharmacological targets. Herein, we conducted full phylogenetic analyses of the deadenylase homologs in all available genomes in an effort to investigate evolutionary relationships between the deadenylase families and to identify invariant residues, which probably play key roles in the function of deadenylation across species. Our study includes both major Asp-Glu-Asp-Asp (DEDD) and exonuclease-endonuclease-phospatase (EEP) deadenylase superfamilies. The phylogenetic analysis has provided us with important information regarding conserved and invariant deadenylase amino acids across species. Knowledge of the phylogenetic properties and evolution of the domain of deadenylases provides the foundation for the targeted drug design in the pharmaceutical industry ...

EMBnet.journal

Nowadays, Deep Learning is taking the world by a storm, known as a technology that makes use of A... more Nowadays, Deep Learning is taking the world by a storm, known as a technology that makes use of Artificial Neural Networks to automatically extrapolate knowledge from a training data set, then uses this knowledge to give predictions for unseen samples. This data driven paradigm gained a widespread adoption in many disciplines, from handwriting recognition, driving an autonomous car to cracking the 50-year-old protein folding problem. With this review, we shed some light on the concepts of Deep Learning and provide some visualizations, skim over the different architectures such as Deep Neural Network (DNN), Convolutional Neural Network (CNN), Recurrent Neural Network (RNN) and touch upon the modern architectures such as Transformers and BERT. We also provide various examples targeting the genomics field, reference utilities, libraries useful for newcomers and disseminate our feedback.

The analysis of adaptive immune repertoires in autoimmune and infectious diseases represents a fa... more The analysis of adaptive immune repertoires in autoimmune and infectious diseases represents a fascinating challenge because of the natural huge diversity of the antigen receptors that are the immunoglobulins or antibodies and T cell receptors, expressed by B cells and T cells, respectively. The high throughput analysis resulting from the next generation sequencing technologies offers an invaluable large scale characterization of the expressed repertoires and, consequently, a better understanding of the protective and pathogenic immune responses. IMGT ® , the international ImMunoGeneTics information system ® (Centre National de la Recherche Scientifique and Montpellier University) is the global reference in immunogenetics and immunoinformatics. By its creation in 1989, IMGT ® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT ® is specialized in the immunoglobulins or antibodies, T cell receptors, major histocompatibility proteins of humans and other vertebrate species, and in the proteins of the immunoglobulin superfamily and major histocompatibility superfamily of any species. IMGT ® has been built on the IMGT-ONTOLOGY axioms and concepts, which bridged the gap between genes, sequences and three-dimensional structures. The concepts include the IMGT ® standardized keywords (identification), IMGT ® standardized labels (description), IMGT ® standardized nomenclature (classification), IMGT unique numbering and IMGT Colliers de Perles (numerotation). IMGT ® comprises seven databases, 15,000 pages of web resources and 17 tools, and includes data from fishes to humans, for basic to veterinary, medical and translational research. IMGT/HighV-QUEST, the high throughput version of IMGT/V-QUEST and IMGT/Junction Analysis, created in 2010, is the first and, so far, the only online portal for analysis of the immunoglobulin and T cell receptor repertoires obtained from next generation sequencing. High-quality results contribute to the large scale vision of antigen receptor repertoires and understanding of the adaptive immune responses (protective in vaccination, cancer and infections and pathogenic in autoimmunity) for diagnosis, prognosis and therapy.

Leukemia, May 25, 2022

The somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gen... more The somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene is a critical biomarker for assessing the prognosis of patients with chronic lymphocytic leukemia (CLL). Importantly, independent studies have documented that IGHV SHM status is also a predictor of responses to therapy, including both chemoimmunotherapy (CIT) and novel, targeted agents. Moreover, immunogenetic analysis in CLL has revealed that different patients may express (quasi)identical, stereotyped B cell receptor immunoglobulin (BcR IG) and are classified into subsets based on this common feature. Patients in certain stereotyped subsets display consistent biology, clinical presentation, and outcome that are distinct from other patients, even with concordant IGHV gene SHM status. All of the above highlights the relevance of immunogenetic analysis in CLL, which is considered a cornerstone for accurate risk stratification and clinical decision making. Recommendations for robust immunogenetic analysis exist thanks to dedicated efforts by ERIC, the European Research Initiative on CLL, covering all test phases, from the pre-analytical and analytical to the post-analytical, pertaining to the analysis, interpretation, and reporting of the findings. That said, these recommendations apply to Sanger sequencing, which is increasingly being superseded by next generation sequencing (NGS), further underscoring the need for an update. Here, we present an overview of the clinical utility of immunogenetics in CLL and update our analytical recommendations with the aim to assist in the refined management of patients with CLL.

Frontiers in Immunology

BackgroundCancer cells activate different immune checkpoint (IC) pathways in order to evade immun... more BackgroundCancer cells activate different immune checkpoint (IC) pathways in order to evade immunosurveillance. Immunotherapies involving ICs either block or stimulate these pathways and enhance the efficiency of the immune system to recognize and attack cancer cells. In this way, the development of monoclonal antibodies (mAbs) targeting ICs has significant success in cancer treatment. Recently, a systematic description of the mechanisms of action (MOA) of the mAbs has been introduced in IMGT/mAb-DB, the IMGT® database dedicated to mAbs for therapeutic applications. The characterization of these antibodies provides a comprehensive understanding of how mAbs work in cancer.MethodsIn depth biocuration taking advantage of the abundant literature data as well as amino acid sequence analyses from mAbs managed in IMGT/2Dstructure-DB, the IMGT® protein database, allowed to define a standardized and consistent description of the MOA of mAbs targeting immune checkpoints in cancer therapy.Resu...

Vaccines, Mar 3, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Methods in molecular biology, 2022

The variable domains (V-DOMAIN) of the antigen receptors, immunoglobulins (IG) or antibodies and ... more The variable domains (V-DOMAIN) of the antigen receptors, immunoglobulins (IG) or antibodies and T cell receptors (TR), which specifically recognize the antigens show a huge diversity in their sequences. This diversity results from the complex mechanisms involved in the synthesis of these domains at the DNA level (rearrangements of the variable (V), diversity (D), and joining (J) genes; N-diversity; and, for the IG, somatic hypermutations). The recognition of V, D, and J as "genes" and their entry in databases mark the creation of IMGT by Marie-Paule Lefranc, and the origin of immunoinformatics in 1989. For 30 years, IMGT ® , the international ImMunoGeneTics information system ® http://www.imgt.org, has implemented databases and developed tools for IG and TR immunoinformatics, based on the IMGT Scientific chart rules and IMGT-ONTOLOGY concepts and axioms, and more particularly, the princeps ones: IMGT genes and alleles (CLASSIFICATION axiom) and the IMGT unique numbering and IMGT Collier de Perles (NUMEROTATION axiom). This chapter describes the online tools for the characterization and annotation of the expressed V-DOMAIN sequences: (a) IMGT/V-QUEST analyzes in detail IG and TR rearranged nucleotide sequences, (b) IMGT/HighV-QUEST is its high throughput version, which includes a module for the identification of IMGT clonotypes and generates immunoprofiles of expressed V, D, and J genes and alleles, (c) IMGT/StatClonotype performs the pairwise comparison of IMGT/HighV-QUEST immunoprofiles, (d) IMGT/DomainGapAlign analyzes amino acid sequences and is frequently used in antibody engineering and humanization, and (e) IMGT/Collier-de-Perles provides two-dimensional (2D) graphical representations of V-DOMAIN, bridging the gap between sequences and 3D structures. These IMGT® tools are widely used in repertoire analyses of the adaptive immune responses in normal and pathological situations and in the design of engineered IG and TR for therapeutic applications.

Springer International Publishing eBooks, 2022

Herein we report the establishment of the 3D structure of the biglycan core protein, using conven... more Herein we report the establishment of the 3D structure of the biglycan core protein, using conventional homology molecular modelling techniques. The 3D model has been structurally optimised via molecular dynamics. It was found that the final model of biglycan resembles in structure its template protein bearing a set of distinct parallel β-sheet structure patterns. The biglycan model bears a very hydrophobic amino acid region towards its inner cavity that acquires an arc-like structure. The external domain of the biglycan model is made up of hydrophilic residues that are exposed to the water solvent. It is those hydrophilic residues that are responsible for their interaction with polysaccharide polymers. Overall comparison of the model of biglycan to the recently determined x-ray structure of the same protein returns a very low Root Mean Square Deviation (RMSD), which confirms the viability of the model and its reliability as a platform for the study biglycan interactions.

The b-ketoacyl carrier protein synthases (the KAS enzymes) are key enzymes that can be used as po... more The b-ketoacyl carrier protein synthases (the KAS enzymes) are key enzymes that can be used as potential anti-Plasmodium drug targets. In bacteria, three KAS enzymes have been identified (KAS I, KAS II and KAS III), whilst in Plasmodium a KAS I/II and KAS III enzyme has been reported. The protein has a total of four active sites, which have been found to be different to each other, rather than four copies of the same active site. The active sites differ not only in the type of interaction they establish with the ligand, but, in the case of Cerulenin as a ligand, the active sites of the KAS I/II enzyme also differ in the number of residues involved in the ligand protein interaction. This is very interesting biochemically, because these differences imply that the affinity of each active site for binding to the ligand might be different as well.

The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) ar... more The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) are characterized by the B and T cells and their specific antigen recep-tors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR) (up to 2.1012 dif-ferent IG and TR per individual). IMGT, the international ImMunoGeneTics information system (http://www.imgt.org), was created in 1989 by Marie-Paule Lefranc (Montpellier Uni-versity and CNRS) to manage the huge and complex diversity of these antigen receptors. IMGT built on IMGT-ONTOLOGY concepts of identification (keywords), description (labels), classification (gene and allele nomenclature) and numerotation (IMGT unique numbering), is at the origin of immunoinformatics, a science at the interface between immunogenetics and bioinformatics. IMGT/HighV-QUEST, the first web portal, and so far the only one, for the next generation sequencing (NGS) analysis of IG and TR, is the paradigm for immune repertoire standardized outputs a...

IMGT R©, the international ImMunoGeneTics informa-tion system R ©

Journal of molecular biochemistry

Herein, we present a novel strategy to analyse and characterize proteins using protein molecular ... more Herein, we present a novel strategy to analyse and characterize proteins using protein molecular electro-static surfaces. Our approach starts by calculating a series of distinct molecular surfaces for each protein that are subsequently flattened out, thus reducing 3D information noise. RGB images are appropriately scaled by means of standard image processing techniques whilst retaining the weight information of each protein's molecular electrostatic surface. Then homogeneous areas in the protein surface are estimated based on unsupervised clustering of the 3D images, while performing similarity searches. This is a computationally fast approach, which efficiently highlights interesting structural areas among a group of proteins. Multiple protein electrostatic surfaces can be combined together and in conjunction with their processed images, they can provide the starting material for protein structural similarity and molecular docking experiments.

Flaviviridae is a family of RNA viruses that includes numerous important human and animal pathoge... more Flaviviridae is a family of RNA viruses that includes numerous important human and animal pathogens. Recent studies on subgenomic flaviviridae replicons have revealed that the non-structural (NS) proteins, which are encoded by the C-terminal part of the polyprotein, play a crucial role in viral RNA replication. Accordingly, these proteins are assumed to form replication complexes in conjunction with genomic RNA and possibly with other cellular factors. One the most important non-structural enzymes that plays a key role in the life cycle of flaviviridae viruses is the viral helicase. Sequence alignments of the viral helicases from this family identified several conserved sequence motifs that are important for biological functions. Herein, an effort is made to summarize the current epidemics associated with the flaviviridae family worldwide, the potential of helicase enzymes as a promising pharmacological target and the use of nucleoside analogs as simple, efficient and rather versatile antiviral agents.

Methods in molecular biology (Clifton, N.J.), 2012

IMGT(®), the international ImMunoGeneTics information system(®) (http://www.imgt.org), was create... more IMGT(®), the international ImMunoGeneTics information system(®) (http://www.imgt.org), was created in 1989 to manage the huge diversity of the antigen receptors, immunoglobulins (IG) or antibodies, and T cell receptors (TR). Standardized sequence and structure analysis of antibody using IMGT(®) databases and tools allows one to bridge, for the first time, the gap between antibody sequences and three-dimensional (3D) structures. This is achieved through the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY concepts of classification (IMGT gene and allele nomenclature), description (IMGT standardized labels), and numerotation (IMGT unique numbering and IMGT Colliers de Perles). IMGT(®) is the international reference for immunogenetics and immunoinformatics and its standards are particularly useful for antibody humanization and evaluation of immunogenicity. IMGT(®) databases for antibody nucleotide sequences and genes include IMGT/LIGM-DB and IMGT/GENE-DB, respectively, whereas n...

Evolutionary Bioinformatics, 2013

The versatility of human immunodeficiency virus (HIV)-1 and its evolutionary potential to elude a... more The versatility of human immunodeficiency virus (HIV)-1 and its evolutionary potential to elude antiretroviral agents by mutating may be its most invincible weapon. Viruses, including HIV, in order to adapt and survive in their environment evolve at extremely fast rates. Given that conventional approaches which have been applied against HIV have failed, novel and more promising approaches must be employed. Recent studies advocate RNA interference (RNAi) as a promising therapeutic tool against HIV In this regard, targeting multiple HIV sites in the context of a combinatorial RNAi-based approach may efficiently stop viral propagation at an early stage. Moreover, large high-throughput RNAi screens are widely used in the fields of drug development and reverse genetics. Computer-based algorithms, bioinformatics, and biostatistical approaches have been employed in traditional medicinal chemistry discovery protocols for low molecular weight compounds. However, the diversity and complexity ...

Evolutionary Bioinformatics, 2013

Deadenylases catalyze the shortening of the poly(A) tail at the messenger ribonucleic acid (mRNA)... more Deadenylases catalyze the shortening of the poly(A) tail at the messenger ribonucleic acid (mRNA) 3′-end in eukaryotes. Therefore, these enzymes influence mRNA decay, and constitute a major emerging group of promising anti-cancer pharmacological targets. Herein, we conducted full phylogenetic analyses of the deadenylase homologs in all available genomes in an effort to investigate evolutionary relationships between the deadenylase families and to identify invariant residues, which probably play key roles in the function of deadenylation across species. Our study includes both major Asp-Glu-Asp-Asp (DEDD) and exonuclease-endonuclease-phospatase (EEP) deadenylase superfamilies. The phylogenetic analysis has provided us with important information regarding conserved and invariant deadenylase amino acids across species. Knowledge of the phylogenetic properties and evolution of the domain of deadenylases provides the foundation for the targeted drug design in the pharmaceutical industry ...

EMBnet.journal

Nowadays, Deep Learning is taking the world by a storm, known as a technology that makes use of A... more Nowadays, Deep Learning is taking the world by a storm, known as a technology that makes use of Artificial Neural Networks to automatically extrapolate knowledge from a training data set, then uses this knowledge to give predictions for unseen samples. This data driven paradigm gained a widespread adoption in many disciplines, from handwriting recognition, driving an autonomous car to cracking the 50-year-old protein folding problem. With this review, we shed some light on the concepts of Deep Learning and provide some visualizations, skim over the different architectures such as Deep Neural Network (DNN), Convolutional Neural Network (CNN), Recurrent Neural Network (RNN) and touch upon the modern architectures such as Transformers and BERT. We also provide various examples targeting the genomics field, reference utilities, libraries useful for newcomers and disseminate our feedback.