LBGI

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Theme : La Bioinformatique et Génomique Intégratives (LBGI)
lbgi.fr

LBGI Bioinformatique et Génomique Intégratives, led by Olivier Poch and Julie Thompson, focuses essentially on an emerging research field, translational bioinformatics in the fields of medicine and health. Our major objective is to develop a robust IT infrastructure capable of managing "big data" and extracting relevant knowledge in a "laboratory to bedside” approach. We are particularly interested in the study of rare diseases and the understanding of the physiopathological mechanisms involved in these diseases, which may improve our understanding of the biological processes that are altered in more common diseases: obesity, diabetes, cancer,...

Translational bioinformatics

Modern biology is characterized by the rapid progress of high-throughput biotechnologies and the production of numerous sets of genome-scale data, the so-called "omics". Thus, the biomedical sciences now have potential access to a huge amount of data which is growing exponentially and covers very different data types, including patient data (of phenotypic, environmental or behavioral origins), omics (genomic environment, gene expressions, enzyme activities, changes in the gene product, etc.), as well as the processes, protocols, or analyses used to produce the information. These biological data sets are distributed on the Internet and are made available in various different formats, which means that the fusion and the exploitation of these heterogeneous data sets are extremely difficult. The situation is further complicated by the fact that the data sets generally contain experimental noise, redundant or missing information and many technical artifacts or bias. To address the challenges posed by this complex data landscape, translational bioinformatics must exploit various high level expertise, ranging from 'big data' management and knowledge discovery, to dynamic complex systems modeling, in order to provide effective solutions for large-scale biomedical studies that can be used by scientists, clinicians and patients. The major objective of the LBGI is to design and develop such automated information systems.

Research axes

The LBGI is dedicated to the development of robust, automated, and integrated in silico approaches (analytical, statistical approaches, data integration and mining, extraction and representation of knowledge...) to study the evolution and behavior of complex biological systems ("hyperstructures", networks, etc.) in humans and various animal models. Taking advantage of our integrated computational approaches and in the context of long-standing international, national and local level collaborations, the LBGI participates in the analysis of complex systems involved in human diseases, including the study of the functional impairments related to retinal or brain diseases, identification of genetic variations linked to ciliopathies and the characterization of the genomic and transcriptomic context in various cancers.

Operations

The work of the LBGI is organized around two major complementary axes:

  • 'Translational informatics' (Julie Thompson), to develop a computational infrastructure dedicated to the integrated analysis of the "big data" resulting from high throughput studies of human genetic diseases. This includes the design and development of original data management systems (data storage, quality control, integration of heterogeneous data) and analysis tools dedicated to data mining and the extraction of biomedical knowledge. An important aspect is the development of intuitive user interfaces to facilitate access by biologists and clinicians.
  • "Systems bioinformatics» (Olivier Poch/Odile Lecompte) to develop research in the emerging field of complex biological systems analysis, in order to understand genotype-phenotype relationships and to answer questions concerning human diseases. This includes integrated studies of evolutionary, omics and patient data, particularly regarding ciliopathies, and the development of a systemic approach to study the relationships between mutations and biological networks in disease.

Projects

Translational informatics

Development of a computational infrastructure dedicated to the integrated analysis of data from "-omics" sciences (cf. www.omics-ethics.org/ fr/definition-science-omics) related to human genetic diseases and health. This infrastructure includes algorithms and original methods, such as:

  • Algorithms and workflows for structural bioinformatics, in the context of a project financed by the French Bioinformatics Institute (IFB), coordinated by P. Tufféry (RPBS, Paris) and D. Ritchie (Loria, Nancy).
  • Algorithms for integrative structural biology, in the context of ongoing funded projects, including the European INSTRUCT research infrastructure for 'Integrative Structural Biology' and the French ANR Investments for the Future project: FRISBI, coordinated by Bruno Klaholtz, IGBMC, Strasbourg.
  • Multi-scale methods for a better understanding of protein properties (structure, interactions, dynamics...) and better integration of the heterogenous data associated with a protein or a family of proteins. Ongoing project, BIPBIP, funded by French ANR in collaboration with Annick Dejaegere, IGBMC, Strasbourg.
  • Evolutionary analyses of protein sequences from NGS data, applied to health, in collaboration with the Data_Mining data mining and SONIC teams.
  • GREMSAP (GRid Evolutionary Multiple Sequence Alignment Platform), in collaboration with the SONIC team, l’Institut des Systèmes Complexes Paris Île de France, l’Institut de Neurobiologie Albert Fressard.
  • Social Network Clinical Database for Intellectual Disabilities: Development of a social network for patients, related to genetic diseases causing developmental disabilities, in collaboration with the SONIC team, the Translational medicine & neurogenetics team, IGBMC, led by Jean-Louis Mandel, and the [http:/www.ucad.sn Cheikh Anta Diop University, Senegal].
  • Infrastructure for 'big data' management for the translational analysis of mutations involved in human genetic disease. BIRD/SM2PH-central is aimed at the integration of heterogeneous data (genomic, phenotypic, evolution, cellular networks,...), with data mining methods (association rules, inductive logic programming,...), and includes the design of a semantic query language (BIRD-QL) and the development of original graphical interfaces. These developments are done in collaboration with Hoan Ngyugen, IGBMC, Strasbourg.

Systems bioinformatics

Development of research in the field of biological systems analysis, to understand genotype-phenotype relationships, notable concerning genetic diseases, and the study of complex biological systems, for example in various cancers or rare diseases (ciliopathies, myopathies,...) in close collaboration with the Human Genetics Laboratory, led by Hélène Dollfus (www.unistra.fr/index.php?id=19264&L=3). The originality of our approach lies in the extraction and exploitation of evolutionary information (sequence analysis, comparative genomics, etc.) in order to improve the analysis of the different levels of complexity in biological systems. Some examples of systems-level projects:

  • Analysis of macromolecular complexes (TFIID...) in collaboration with the Department of Integrative structural biology, IGBMC.
  • Analysis of organelles (exosome, endosome...) in collaboration with the membrane traffic and lipid signaling team, GMGM: synthetic yeast evolution, the characterization of the shared / specific features at different levels (nucleotide, gene, pathway), the identification of correlations between the evolutionary scenarios and the modifications identified in the molecular processes.
  • Genomic analysis of 1000 myopathy patients (Myocapture project and ongoing FRM-funded project, in collaboration with le team of Jocelyn Laporte, IGBMC) with the goal of identifying and characterizing new genes in these diseases.
  • Analysis of genomic data from ciliopathy patients (Bardet-Biedl Syndrome and Alström Syndrome) to identify the genes responsible for the diseases, and to understand the links between genotypes/phenotypes, in collaboration with Human Genetics Laboratory, led by Hélène Dollfus.
  • Integration of "omics" data to develop a new generation of the Vaccinia virus (VACV). Ongoing funded project (OncoVaccine: ANR Recherches Partenariales et Innovation Biomédicale) in collaboration with TRANSGENE, the HTCS platform led by Laurent Brino, IGBMC and the team of Etienne Weiss, IREBS, Strasbourg.
  • ImAnno is a collaborative project between the LBGI and teams at the IGBMC, Strasbourg (P. Dollé) and the Institute of Vision, Paris (J. Sahel, T. Leveillard) aimed at developing an ergonomic and integrative annotation tool for biological images (ISH, fundus...). Once annotated, the images allow to access all the knowledge extraction tools implemented or developed by the LBGI, including protein-protein interaction networks, tools for automatic analysis of the evolution, transcriptomic data, etc.
  • Multi-scale tempo-spatial modeling of the primary cilia as a means of communication (intracellular transport, physical cell-cell interactions, environmental sensory system) and its role in the cell cycle, development, as well as the evolution of eukaryotic organisms, in collaboration with the Digital Campus for Complex Systems.

Collaborations

Our projects, ranging from low level molecular studies to clinical applications, require close collaborations with computer scientists and theoretical bioinformaticians (including the BFO team), and close links with researchers in experimental and medical biology, notably at the IGBMC and the Strasbourg Faculty of Medicine, to develop or improve the algorithms in the context of translational medicine.

Bioinformatics software development:

  • French Bioinformatics Institute (IFB)
  • INSTRUCT European Consortium
  • FRISBI French Consortium
  • BIP:BIP (Bayesian inference paradigm: Biology in processors) Consortium
  • GJ. Barton; Univeristy of Dundee, Scotland
  • P. Collet, N. Lachiche, P. Gançarski; ICube, Strasbourg
  • A. Dejaegere; IGBMC, Strasbourg
  • MD. Devignes; LORIA, Nancy
  • TJ. Gibson; EMBL, Heidelberg, Germany
  • DG. Higgins; University College Dublin, Ireland
  • P. Jollivet; Station Biologique de Roscoff
  • B. Klaholz; IGBMC, Strasbourg
  • P. Koehl; UC Davis, USA
  • G. Labesse; CBS, Montpellier
  • C. Marino Buslje; Uni. Buenos Aires, Argentina
  • C. Mayer; Institut Pasteur, Paris
  • D. Moras; IGBMC, Strasbourg
  • P. Pontarotti; Marseille
  • E. Pontelli; University of New Mexico, USA
  • AK. Royyuru; IBM Watson, USA
  • P. Schultz; IGBMC, Strasbourg
  • P Sempé, X. Mary; IBM France
  • A. Stoltzfus; NIST, USA
  • A. Van Dorsselaer; IPHC, Strasbourg

Database development:

  • P. Bork; EMBL, Heidelberg, Germany
  • P. Dollé; IGBMC, Strasbourg
  • W. Krezel; IGBMC, Strasbourg
  • A. Pujol; Barcelona University, Spain

Ciliopathies:

  • H. Dollfus; LGM, Strasbourg
  • JL. Mandel ; IGBMC, Strasbourg

Myopathies/AFM Décrypthon:

  • J. Laporte; IGBMC, Strasbourg
  • C. Marcelle; Melbourne University, Australia
  • T. Toursel; AFM, Paris

Retinal disease:

  • AMD Consortium (7 worldwide teams)
  • EVI-Genoret Consortium (42 European teams)
  • I. Audo; Université Pierre et Marie Curie, Paris
  • S. Bhattacharya; Inst. Ophthalmology, London, UK
  • J. Demongeot; U. Joseph Fourier, Grenoble
  • C. Grimm; Zurich, Switzerland
  • T. Léveillard; Institut de la Vision, Paris
  • J. Sahel; Institut de la Vision, Paris
  • D. Zack; John Hopkins Hospital, Baltimore USA
  • C. Zeitz; Institut de la Vision, Paris

Prostate cancer:

  • J. Abecassis, IGBMC, Strasbourg
  • M. Cecchini; University of Bern, Switzerland
  • J. Schalken; NCMLS, Nijmegen, Netherland
  • B. Wazylick; IGBMC, Strasbourg

Functional genomics data analysis:

  • TF. Baumert; UdS, Strasbourg
  • B. Bihain; Genclis SAS, Nancy
  • A. Bloch-Zupan; IGBMC, Strasbourg
  • P. Carbon; IBMC, Strasbourg
  • C. da Silva; Génoscope ; Evry
  • E. Friedrich; University of Luxembourg
  • J. Laporte; IGBMC, Strasbourg
  • V Laudet; ENS, Lyon
  • A. Marchini; University of Heidelberg, Germany
  • R. Romand; IGBMC, Strasbourg
  • M. Roux; INIST, Nancy
  • M. Sissler; IBMC, Strasbourg
  • L. Tora; IGBMC, Strasbourg
  • L. Vallar; CRP-Santé, Luxembourg

Publications

A complete list of our publications is available here.