Integrative genomics
The Integrative Genomics in Neurodevelopment group gathers members interested in normal and diseased brain development, and mainly focuses on statistical and computational biology approaches to integrate -omics data from patients, healthy individuals, animal or in vitro models. Our research applies to neurodevelopmental and neuropsychiatric disorders especially epilepsy, bipolar disorders, and complications of prematurity.
A.D.D
A.D.D
We develop tools to analyze and combine newly generated and existing open-source data. Genome-wide transcriptional profiling, using spatial or single-cell transcriptomics, can help to identify candidate regulators and drivers of the disease under investigation. Our methodological research emphasizes on gene regulatory networks and network analysis to prioritize key regulators that govern developmental and pathological processes. In order to study mood disorders, we use integration of multi-omics data (mRNA-seq, miRNA-seq, methylomes, and GWAS) with phenotype data from patients to identify candidate biomarkers and to help to stratify patient groups. Beyond a better understanding of molecular drivers of neurodevelopment and neuropsychiatric disorders, we aim at providing new candidate targets for drug discovery and repurposing. To this purpose, we currently study the use of machine learning methods to repurpose drugs based on their transcriptional impact.
VS3600: Integrated AI-assisted virtual screening pipelines and database mining to assist early stages drug discovery and foster actionable knowledge (Bruno Villoutreix)
The aim of virtual screening (VS) is to identify
bioactive compounds (small molecules, short peptides…) through computational means by using as input the 3D structure of a putative protein target (structure-based VS) and/or known
bioactive molecules against this selected target (ligand-based VS). In VS, a large number of
molecules (approved drugs, already synthesized compounds, virtual compounds) are ranked according to their likelihood of being bioactive using different metrics. The top fraction of the resulting predicted list can then be tested experimentally. Modified VS algorithms can also be used to predict off-targets and anti-targets, drug combination, multi-target drugs… While such computations assist decision making, in real life scenario, many other information are needed so as to get a panoramic view about the investigated drug-target-disease axis (e.g., projection of the compounds onto the human interactome, onto disease pathways, consideration of ADMET properties…). We develop VS360O, a tool that combines LBVS and SBVS and various data mining approaches so as to generate a comprehensive profile around the investigated system (i.e., a 360o view with integrated experimental and predicted data). VS360O can be used for drug repurposing, to discover novel high quality compounds and novel targets/pathways/mechanisms. The tool can be easily combined with experimental methods and should definitively contribute to de-risking therapeutic development in an academic setting.
Contacts
Andrée Delahaye-Duriez
Inserm U1141 – NeuroDiderot
Robert Debré Hospital
48 Boulevard Sérurier
75019 Paris
andree.delahaye@insem.fr
Bruno Villoutreix
Inserm U1141 – NeuroDiderot
Robert Debré Hospital
48 Boulevard Sérurier
75019 Paris
bruno.villoutreix@inserm.fr
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Job opportunity within The Integrative Genomics in Neurodevelopment group
The Integrative Genomics in Neurodevelopment group is seeking a highly motivated post-doctoral researcher. Check out the opportunity here: Post-doc researcher position in Computational Biology
Sleep2Develop research program
The Sleep2Develop program investigates the role of sleep as a promotor of neurodevelopment and identifies the sleep determinants of childhood development. This is rephrased as Sleep(to)Develop? or Sleep(to)Develop! Our sleep research combines clinical and...
Job opportunity
NemoClinics platform is hiring an engineer. Check out the opportunity here: U 1141 -Ingénieur-e en expérimentation et instrumentation biologiques- CDD 2023 Read more
Research program on CCHS
CCHS is a disease characterized by a congenital impairment of the central control of breathing, associated with dysfunctions of the autonomic nervous system (ANS) (Gallego, 2012). At birth, patients have severe and persistent hypoventilation during sleep and a...