Evolutionary and Medical Genomics

Leader: Odile LECOMPTE

Participants: Nathalie AL MAKDESSI, Ali AYADI, Anne JEANNIN, Claudine MAYER, Christian MICHEL, Luc MOULINIER, Olivier POCH, Laetitia POIDEVIN, Jean-Sébastien SERENI, Julie THOMPSON

Post-doctoral researcher : Kirsley CHENNEN

Engineer : Arnaud KRESS

PhD students : Lena BONASSIN, Luka Ljudevit BOSTJANCIC, Nicolas Haas, Hiba KHODJI, Dorine MERLAT, Corentin MEYER, Quentin Rott, Christelle RUTZ, Alix SIMON

Objectives and approaches

Our work is focused on knowledge extraction from omics data (genomes, transcriptomes, proteomes, metabolomes, lipidomes, interactomes) with two main objectives:

The characterization of genotype/phenotype relationships, in particular in the context of complex genetic diseases
The understanding of the evolution of biological systems, either biological processes or species.

To achive this, we use and develop a wide range of approaches:

analysis of biological sequences
study of sequence/structure/function relationships
intra- and inter-species comparative genomics
graphs
artificial intelligence

One of the specificities of our team lies in the exploitation of traditional bioinformatics methods to generate knowledge that can then guide artificial intelligence approaches. This original combination is based on the plurality and complementarity of the team's in-house skills.

Application domains and current projects

=== Health: complex genetic diseases and cancers We rely on close and long-lasting collaborations with the medical field, within the Strasbourg Biomedicine Research Center (CRBS), at the local level (IGBMC, IBMC, Faculty of Pharmacy), at the national level with the teams of the Institut de la Vision in Paris or at the European level with our participation in the Rare Genetic Diseases WorkPackage of the European project Elixir-Excelerate. These collaborations allow us to benefit from the expertise of clinicians, particularly in terms of phenotyping, and to access large volumes of patient data, including genomic and phenotypic (imaging, histological, metabolomic, environmental) data.

These collaborations concern in particular:

ciliopathies
myopathies
eye diseases
obesity
pediatric gliomas

Evolution and Biodiversity

Evolution of decapod genomes

Decapod genomes show considerable variation in size. We are currently sequencing the giant genome of the noble crayfish Astacus astacus (17 Gb), a European species currently threatened by crayfish plague. This genome will be compared to other available decapod genomes to understand the evolution of chromosome organization, gene repertoires and repeating elements. This project is carried out in collaboration with the LOEWE Centre for Translational Biodiversity Genomics in Frankfurt and is funded by ANR/DFG. It is part of the ERGA (European Reference Genome Atlas) initiative.

The genome coupled with complementary omics data will also be used to identify the molecular basis of immunity in crayfish and to understand the differences in resistance to crayfish plague observed between populations in order to allow, in the long term, the reintroduction of resistant individuals.

Genomic exploration of Myriapod diversity

We are working on the annotation and comparison of 20 Myriapod genomes. Myriapods (millipedes) are essential invertebrates for the biodiversity of the soil but are still largely unknown at the genomic level. The comparative analysis of these genomes should allow us to learn more about metamerization, the ancestral genome of arthropods and the adaptation of species to more or less anthropized environments. This study is part of the collaborative project MetaInvert which aims to characterize the genomes of soil invertebrates and to establish correlations between genomic and ecological traits. The genomes will then serve as a reference for the identification and quantification of individuals by metagenomic approaches.

Resource development (knowledge bases and software)

PipeAlign2 : suite of programs dedicated to protein family analysis
PROBE : analysis and visualization of conservations within a multiple alignment
OrthoInspector : program and databases of orthology relations covering the 3 domains of life
BLUR : analysis of divergences between proteomes between taxa (presence/absence of genes or domains, divergence of regions between orthologues)
MISTIC : prediction of variant effects
Spliceator : prediction of splice sites