Je présenterai les transformations actuelles des structures en faveur de l’intégrité scientifique en France et dans le monde et je passerai en revue différentes facettes de l’intégrité scientifique, de la réflexion méthodologique aux règles de promotion et de recrutement, en passant par le soin que l’on doit porter collectivement aux données et l’incitation à la science ouverte.

How did evolution emerge in physical-chemical systems during the origin of life? Reproduction requires autocatalysis, but evolution further requires a diversity of autocatalytic systems. In a first study, we found universal stoichiometric criteria to recognize autocatalysis in reaction networks. This analysis unifies our view of self-reproductionin already known systems and indicates that there may exist many others. In a second study, we experimentally measured the dynamics of thousands of autocatalytic RNA reaction networks. The resulting landscape reveals trade-offs between the Darwinian properties of variation and selection in self-reproducing systems. Finally, I will discuss how Darwinian evolution may ultimately be implemented in RNA recombination networks. Bibliography [1] Ameta, S., Arsène, S., Foulon, S., Saudemont, B., Clifton, B. E., Griffiths, A. D., & Nghe, P. (2021). Darwinian properties and theirtrade-offs in autocatalytic RNA reaction networks, Nature Communications (2021, in press) [2] Blokhuis, A., Lacoste, D., & Nghe, P., Universal motifs and the diversity of autocatalytic systems. Proceedings of the National Academyof Sciences, 117(41), 25230-25236…

Comparative genomics studies are central in identifying the coding and non-coding elements associated with complex traits, and the functional annotation of genomes is a critical step to decipher the genotype-to-phenotype relationships in livestock animals. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project aimed to create reference functional maps of domesticated animals by profiling the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells). RNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs. ATAC-seq highlighted an enrichment for transcription factor binding sites in differentially accessible regions of the chromatin. Comparative analyses revealed a core set of conserved regulatory regions across species. Topologically associating domains (TADs) and epigenetic…

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I will describe two projects going on in my lab: 1) CACTUS: integrating clonal architecture with genomic clustering and transcriptome profiling of single tumor cells and 2) Interpretable deep recommender system model for prediction of kinase inhibitor efficacy across cancer cell lines. Below I provide a short summary for both of them.1) CACTUS: integrating clonal architecture with genomic clustering and transcriptome profiling of single tumor cells  Drawing genotype-to-phenotype maps in tumors is of paramount importance for understanding tumor heterogeneity. Assignment of single cells to their tumor clones of origin can be approached by matching the genotypes of the clones to the mutations found in RNA sequencing of the cells. CACTUS is a probabilistic model that leverages the information from an independent genomic clustering of cells and exploits the scarce single cell RNA sequencing data to map single cells to given imperfect genotypes of tumor clones. We apply CACTUS to two follicular lymphoma patient samples, integrating three…

To understand the sequence relationships between many genomes, we build a graphical data structure that represents their mutual alignment. This pangenome graph can serve as a powerful tool for research into genome variation, selection, and evolution. Generating and refining pangenome graphs is an area of active research that has necessitated the development of novel alignment and graph induction methods. We discuss these issues in detail and illustrate how they are addressed in the pangenome graph builder tool (pggb). We close with an overview of the application of our approach to the 90 haplotypes in the year 1 assemblies of the Human Pangenome Project, where our method provides an unprecedented view of variation in the full human pangenome.

Cancer is a genetic disease, where cell division, mutation and selection produce a heterogeneous tumor composed of multiple subpopulations of cells with different sets of mutations. During later stages of cancer progression, cancerous cells from the primary tumor migrate and seed metastases at distant anatomical sites. The cell division and mutation history of an individual tumor can be represented by a phylogenetic tree, which helps guide patient-specific treatments. In this talk, I will introduce combinatorial algorithms for reconstructing tumor phylogenies from bulk DNA sequencing data, where the measurements are a mixture of thousands of cells. These algorithms are based on a combinatorial characterization of phylogenetic trees as a restricted class of spanning trees in a graph, a characterization that also demonstrates the computational complexity of the problem. In addition, I will introduce a novel framework for analyzing the history of cellular migrations between anatomical sites in metastatic cancers. Finally, I will discuss…