Who Does What in Component LBGI within Thematics
Responsible : Julie Thompson
Participants : Julie Thompson
Description : The last decade has provided access to a large amount of data resulting from high throughput genomic technologies, such as transcriptomics, proteomics or interactomics. However, this large scale accumulation of data is only a necessary preliminary in the understanding of the principles and fundamental mechanisms of life. Comparative sequence analyses and phylogenetic inferences play an essential role in the biological systems studies aimed at understanding this new data.
In this context, we are developing an expert system, AlexSys, for the construction, refinement, analysis and exploitation of multiple sequence alignments, combining diverse, complementary algorithms and incorporating additional information (structural, functional and evolutionary). A prototype platform is now available, built on the Unstructured Information Management Architecture (UIMA). The alignment methodology is based on ClustalW, but integrates several more powerful algorithms that significantly increase the efficiency and the quality of the multiple alignment. AlexSys also includes a number of diagnostic tests that allow us to automatically select the most suitable alignment algorithm, depending on the set of sequences to be aligned and the biological application.
The modular design of AlexSys facilitates the incorporation of new algorithms and will allow its continued evolution. In the future, we will incorporate more diverse components, covering aspects of genomic and protein data mining, validation and integration of structural/functional data, integrated with a set of different algorithms.
Responsible : Nicolas Gagnière, Odile Lecompte
Participants : Odile Lecompte, Olivier Poch, Raymond Ripp
Description :
Responsible : Ngoc-Hoan Nguyen
Participants : Luc Moulinier, Ngoc-Hoan Nguyen, Laetitia Poidevin, Raymond Ripp, Vincent Walter
Description : Biological Integration and Retrievial Data
Responsible : Yann Brelivet
Participants : Yann Brelivet, Raymond Ripp
Description :
Responsible : Julie Thompson
Participants : Julie Thompson
Description : The term "Evolutionary Informatics" emphasizes the informatics aspects of evolutionary analysis, which is a kind of comparative analysis. We are participating in the EvoInfo working group funded by NESCent (http://www.nescent.org/).
The growth of bioinformatics and genomics presents a wealth of opportunities for expanded application of evolutionary methods-- expanded with respect to both the amount and the variety of analyses. Powerful tools for evolutionary analysis already exist, but integrating evolutionary methodology into biological data analysis does not depend so much on the power of tools as it does on infrastructure. To address these infrastrutural needs, the EvoInfo working group will develop community cohesion on issues of standards and interoperability, and will facilitate (directly and indirectly) development of interoperable software and data standards.
In this context, we are participating in the development of a Comparative Data Analysis Ontology (CDAO). (https://www.nescent.org/wg_evoinfo/CDAO)
Responsible : Julie Thompson
Participants : Benjamin Linard, Olivier Poch, Julie Thompson
Description : The genetic information encoded in the genome sequence contains the blueprint for the potential development and activity of an organism. This information can only be fully comprehended in the light of the evolutionary events (duplication, loss, recombination, mutation…) acting on the genome, that are reflected in changes in the sequence, structure and function of the gene products (nucleic acids and proteins) and ultimately, in the biological complexity of the organism.
The recent availability of the complete genome sequences of a large number of model organisms means that we can now begin to understand the mechanisms involved in the evolution of the genome and their consequences in the study of biological systems. This is illustrated by the evolutionary analyses and phylogenetic inferences that play an important role in most functional genomics studies, e.g. of promoters (‘phylogenetic footprinting’), of interactomes (notion of ‘interologs’ based on the presence and degree of conservation of counterparts of interactive proteins), and also, in comparisons of transcriptomes or proteomes (notion of phylogenetic proximity and co-regulation/co-expression).
At the same time, theoretical advances in information representation and management have revolutionised the way experimental information is collected, stored and exploited. Ontologies, such as Gene Ontology (GO) or Sequence Ontology (SO), provide a formal representation of the data for automatic, high-throughput data parsing by computers. These ontologies are being exploited in the new information management systems to allow large scale data mining, pattern discovery and knowledge inference.
Unfortunately, the vast number and complexity of the events shaping eukaryotic genomes means that a complete understanding of evolution at the genomic level is not currently feasible. At the lowest level, point mutations affect individual nucleotides. At a higher level, large chromosomal segments undergo duplication, lateral transfer, inversion, transposition, deletion and insertion. Ultimately, whole genomes are involved in processes of hybridization, polyploidization and endosymbiosis, often leading to rapid speciation.
We will characterise and study the evolutionary histories of the human proteome, defined as the impact in the human proteins (extensions, insertions, deletions…) of the cascade of genetic events (duplication, lateral transfer, inversion, transposition, deletion, insertion…) that occurred during the evolution of the vertebrate genomes. This ambitious objective is now possible thanks to the emergence of formal descriptions of biological data and to the recent developments of accurate phylogenetic reconstruction and genome analyses (Partner 1: Figenix platform) and of automated reliable and exploitable protein sequence alignments (TCOFFEE, PipeAlign, MAO, MACSIMS…). These methodologies will be combined into a multi-agent, expert system for the construction of evolutionary histories. In order to facilitate the automatic definition of the important genetic events shaping a single protein and their potential causalities at the genome level, a new ontology will be developed. In a subsequent step, the evolutionary histories of the complete human proteome will be reconstructed, followed by their classification into protein sets sharing typical evolutionary histories, and the functional analysis of these sets. An analysis at the genomic level will be realized for a specific number of proteins identified in the classification and functional analysis step.
Responsible : Raymond Ripp
Participants : Laetitia Poidevin, Raymond Ripp
Description :
Responsible : Laetitia Poidevin
Participants : Olivier Poch, Laetitia Poidevin, Raymond Ripp
Description :
Responsible : Raymond Ripp
Participants : Odile Lecompte, Luc Moulinier, Laetitia Poidevin, Raymond Ripp
Description : Gscope is an integrated platform allowing the analysis of all kind of genomic data.
Gscope is written in Tcl/Tk and runs on all systems.
Gscope is specially designed to perform high throughput analysis.
Gscope is mainly composed of all tools necessary to create the basic data, analysis tools, visualisation interface, it allows also the creation and feeding of SQL relational databases, the quering and display of the available information through a web based interface (Wscope)
See Wiki Gscope
Responsible : Wolfgang Raffelsberger
Participants : Olivier Poch, Wolfgang Raffelsberger
Description : Oncolytic H-1 ParvoVirus RNAi screen INCa platform project; LBGI/Bips (O Poch, W Raffelsberger) in collaboration with high-throughput transfection platform (P Oudet/L Brino), Inserm Unité 701 (DKFZ) (A Marchini) and transcriptomics platform IGBMC (P Kastner).
De part leur tropisme naturel pour les cellules tumorales, leur activité oncolytique et l’absence de symptomes lors d’infections chez l’homme, les petits virus de la famille des parvovirus (type MVM, H1 et LuIII) présentent un grand potentiel pour le développement de nouvelles stratégies de traitement du cancer.
La protéine non structurale NS1 est essentielle pour la réplication de l’ADN viral, l’expression de gènes viraux et est un des effecteurs majeurs de l’activité oncolytique des parvovirus.
Cependant, la connaissance du cycle de vie de ces virus, des facteurs cellulaires impliqués et des mécanismes oncolytiques associés reste fragmentaire.
Les objectifs :
i) identifier et caractériser fonctionnellement les déterminants moléculaires impliqués dans les étapes précoces de l’entrée et de la transduction des parvovirus,
ii) identifier les voies cellulaires activées en réponse à l’infection virale et notamment celles impliquées dans leur activité oncolytique.
Responsible : Sophie Candel
Participants : Radhouene Aniba, Sophie Candel, Frederic Plewniak
Description : Intelligent BioInformatics Solutions Software Architecture
with UIMA
Responsible : Wolfgang Raffelsberger
Participants : Olivier Poch, Wolfgang Raffelsberger
Description : Prognistic and predictive values of high-resolution molecular DNA markers in non-small cell lung cancers (NSCLC) of IFCT-00-02 trial (phase III studycomparing a reoperative and chemotherapy with two different chemotherapy regimes in resectable NSCLC)
Acronym: BIO IFCT-00-02 II
Collaboriation with M Beau-Faller and P Oudet (Hautpierre)
Responsible : Julie Thompson
Participants : Julie Thompson
Description : Our team will characterize of the total set of mouse proteins involved directly or indirectly in the transcriptional processes. This will require an in depth sequence, structural, evolutionary (SSE) and functional analysis of the mouse proteome with the major objective of defining and delineating any conserved domains or regions that might be associated to known transcriptional modules. This work will be performed in collaboration with M. Andrade’s team (Ottawa, Canada) in the context of the International Regulome Consortium (http://www.internationalregulomeconsortium.ca/). In the framework of the proposed Decrypthon project, the SSE analysis of the entire human/mouse proteome (~60 000 proteins including splice variants and the human or mouse specific proteins) will involve a pipeline of processes starting with homology identification, multiple sequence alignment, structural and functional subfamily classification, orthology/paralogy analysis and phylogenetic reconstruction. We will take advantage of the previous developments performed on the Decrypthon grid, notably those concerning the MACSIMS (Multiple Alignment of Complete Sequence Information Management System) functional annotation and new protocols will be developed including PSI-Blast searches to detect distantly related proteins, recent multiple alignment algorithms implementation and phylogenetic tree algorithms. Protocols ensuring automated updating and storage in a relational database, hosted by the Decrypthon, will be developed. The results will be combined with the data from the transcriptomal analysis performed in vivo. This complementary approach is expected to help us to identify and characterise the transcriptional networks involved in muscle development, specification, regeneration and myogenic progression. In vivo functional validation will be done using mouse molecular genetics and expertise in muscle biology in the laboratory of F. Relaix.
Responsible : Raymond Ripp
Participants : Laetitia Poidevin, Wolfgang Raffelsberger, Raymond Ripp
Description :
Responsible : Ngoc-Hoan Nguyen
Participants : Luc Moulinier, Ngoc-Hoan Nguyen, Raymond Ripp, Vincent Walter
Description : De la Mutation Structurale aux Phénotypes des Pathologies Humaines