Adrien Foucal
A5039491821- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Genetic diversity and population structure
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Forensic and Genetic Research
- Cancer-related gene regulation
- Prostate Cancer Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Evolution and Genetic Dynamics
- Cancer-related molecular mechanisms research
- Developmental Biology and Gene Regulation
- Prenatal Screening and Diagnostics
- Genetic Mapping and Diversity in Plants and Animals
- Cardiac Valve Diseases and Treatments
- Circular RNAs in diseases
- Genetic factors in colorectal cancer
- CRISPR and Genetic Engineering
- Genetic and phenotypic traits in livestock
- RNA Research and Splicing
- Genomics and Rare Diseases
- Genomics and Chromatin Dynamics
- Cardiomyopathy and Myosin Studies
Ontario Institute for Cancer Research
2019-2025
Research Canada
2025
Institut du Thorax
2020-2024
Centre Hospitalier Universitaire de Nantes
2024
Inserm
2020-2022
Centre National de la Recherche Scientifique
2020-2022
Nantes Université
2020-2022
University of Bern
2014-2017
SIB Swiss Institute of Bioinformatics
2014-2017
Significance The domestication of the horse revolutionized warfare, trade, and exchange people ideas. This at least 5,500-y-long process, which ultimately transformed wild horses into hundreds breeds living today, is difficult to reconstruct from archeological data modern genetics alone. We therefore sequenced two complete genomes, predating by thousands years, characterize genetic footprint domestication. These ancient genomes reveal predomestic population structure a significant fraction...
Abstract Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as grade. To interrogate the evolutionary origins cancer heterogeneity, we analyzed 666 whole genomes. We identified a compendium 223 recurrently mutated driver regions, influencing downstream processes gene expression. validated individual germline variants that predispose tumors to acquire specific...
Humans have colonized the planet through a series of range expansions, which deeply impacted genetic diversity in newly settled areas and potentially increased frequency deleterious mutations on expanding wave fronts. To test this prediction, we studied genomic French Canadians who Quebec 17th century. We used historical information records from ∼4000 ascending genealogies to select individuals whose ancestors lived mostly colonizing front remained core settlement. Comparison exomic reveals...
Abstract While 3D chromatin organization in topologically associating domains (TADs) and loops mediating regulatory element-promoter interactions is crucial for tissue-specific gene regulation, the extent of their involvement human Mendelian disease largely unknown. Here, we identify 7 families presenting a new cardiac entity associated with heterozygous deletion 2 CTCF binding sites on 4q25, inducing TAD fusion conformation remodeling. The are located desert at 1 Mb from Paired-like...
Abstract Prostate cancer is characterized by profound clinical and molecular heterogeneity. While its genomic heterogeneity well-characterized, epigenomic remains less understood. We therefore created a compendium of 3,001 multi-ancestry prostate methylomes spanning normal tissue through localized disease all grades to poly-metastatic disease. A subset 884 samples had multi-omic DNA and/or RNA characterization. identify four subtypes that risk-stratify patients reflect distinct evolutionary...
<p>Mutational hallmarks of prostate cancer grade. <b>A,</b> A linear model was fit to relate each mutational density measure ISUP GG using tumor and normal sequencing coverage as covariates. Dot size color represents the effect for a <i>Z</i>-score relative 1. The barplot right shows <i>Q</i> value from nonparametric Kruskal–Wallis test. <b>B,</b> Distribution number driver mutations per in GG; median is shown by black dot....
<div>Abstract<p>Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as grade. To interrogate the evolutionary origins cancer heterogeneity, we analyzed 666 whole genomes. We identified a compendium 223 recurrently mutated driver regions, influencing downstream processes gene expression. validated individual germline variants that predispose tumors...
<p>Functional characterization of driver mutations. <b>A,</b> Network diagrams represent multimodal pathway enrichment analysis genes. Mutation types (i.e., the type analysis) are indicated by shading circles. Circle size represents number patients. Heatmaps show mutations in cohort that affect genes contributing to two exemplar pathways dysregulated multiple mutation types. The apoptosis (GO:0042771 – intrinsic apoptotic signaling response DNA damage p53 class mediator),...
<p>Supplementary Figures & Figure Legends. Supplementary 1 | Cohort Structure and Analysis. 2 CNA Evolution Transcriptomic Effects. 3 Properties of Driver Mutations. 4 Pathway Signature Analysis Genes. 5 Patterns Mutational Drivers. 6 Molecular Correlates Clinical Behavior. 7 Heterogeneity Driver-Clinical Associations. 8 Characteristics Risk dQTL Replication. 9 Local dQTLs Discovery. 10 Replication dQTLs. 11 Enrichment Sub-threshold 12 Characterization 13 Association SNPs with eQTL...
<p>Somatic driver mutations in localized prostate cancer. Driver mutation discovery 666 tumors. The top barplot shows the distribution of number drivers patients; covariates on left show region type and statistical significance from ActiveDriverWGS GISTIC. heatmap found this study (rows) for each patient (columns). bottom an exome meta-analysis (<a href="#bib14" target="_blank">14</a>). Heatmaps are colored by type. Right per patient. Bottom covariate bars clinical features...
<p>dQTLs bias somatic mutational landscape. <b>A,</b> Schematic of dQTL detection. The PRS used was by Schumacher and colleagues (<a href="#bib16" target="_blank">16</a>). Linear local dQTLs were assessed within ±500 kbp around a driver. Spatial evaluated using regions defined RNA Pol-II ChIA-PET profiling in LNCaP, DU145, VCaP, RWPE-1 cell lines RAD21 LNCaP DU145 cells. Enhancer H3K27ac HiChIP All discovered tested for replication six cohorts....
<p>Mutational subtypes of localized prostate cancer. <b>A,</b> Mutation densities (rows) differ by ETS fusion and <i>NKX3-1</i> CNA status (columns). Dot size color gives effect-size as a <i>Z</i>-score, scaled to ETS-negative, <i>NKX3-1</i>–neutral patients. The barplot on the right shows FDR-adjusted <i>P</i> values from nonparametric Kruskal–Wallis tests. <b>B,</b> Comparison...
<p>Characterization of dQTLs. <b>A,</b> Summary all 35 dQTLs involving 25 unique SNPs. Dot size and color indicate the magnitude direction association (as OR), background shading indicates dQTL discovered strategy. <b>B,</b> Forest plot OR 95% confidence interval for associations across 1,991 prostate tumors. Background <i>Q</i> < 0.1. The middle covariate driver mutation, right heatmap cohorts included in analysis. <b>C,</b> molecular...