Guillaume Lettre

Integrated genotyping, annotation and epigenetic characterization of transposable elements with GraffiTE

GraffiTE v1.1 is a Nextflow pipeline that genotypes structural variants, annotates polymorphic mobile elements, and maps epigenetic data to transposable elements using pangenome graphs, revealing hypomethylated elements and age-related demethylation.

Comparing bulk and single-cell methodologies and models to profile gene expression, chromatin accessibility and regulatory links in endothelial cells treated with TNFα

The paper compares bulk and single-cell RNA-seq/ATAC-seq data and models to assess their impact on predicting causal genes from GWAS variants in TNFα-treated endothelial cells.

Proteogenomic analysis of 5,411 plasma proteins in sickle cell disease patients

The paper identifies 560 plasma protein quantitative trait loci (pQTL) in sickle cell disease patients and links them to HbF production through Mendelian randomization.

Genetic contribution to asthma informs acute chest syndrome pathophysiology and risk stratification

This study uses polygenic scores to show asthma genetics are linked to ACS recurrence risk, but not occurrence, and highlights the role of HbF in modulating this risk.

A multi-ancestry genetic reference for the Quebec population

The paper constructs a genetic reference panel for the Quebec population using whole-genome sequencing and GWAS to improve phenotype-genotype association discovery.

Pooled CRISPR screens identify genes and non-coding genomic regions that regulate red blood cell density

The paper uses CRISPR screens to identify genes and non-coding regions affecting red blood cell density, finding 17 genes and 13 regions, some novel, that regulate this trait.

LIPTER, a cardiomyocyte-enriched long noncoding RNA, controls cardiac cytoskeletal maturation and is regulated by a cardiomyocyte-specific enhancer.

The paper identifies LIPTER, a cardiomyocyte-specific long noncoding RNA, and shows it regulates cytoskeletal maturation and is controlled by a cardiomyocyte-specific enhancer.

Single-cell transcriptomic analyses unveil exercise-induced changes in murine skin vascular endothelial cells

The paper uses single-cell RNA sequencing to show exercise increases Zbtb16 expression and suppresses oxidative stress and metabolism in murine skin vascular endothelial cells.

Using the ancestral recombination graph to study the history of rare variants in founder populations

This paper uses ancestral recombination graphs to impute and trace rare variants in founder populations, showing high accuracy in mutation age and regional frequency estimation.

Robust fine-mapping in the presence of linkage disequilibrium mismatch

RSparsePro improves fine-mapping accuracy in the presence of LD mismatch by using a probabilistic graphical model and variational inference, outperforming SuSiE in simulations and real applications.

Replication of a GWAS signal near HLA-DQA2 with acute myeloid leukemia using a disease-only cohort and external population-based controls

The paper replicates a GWAS signal near HLA-DQA2 associated with AML risk using a disease-only cohort and external population-based controls, finding a stronger effect in patients with NPM1 mutations.

Joint genotypic and phenotypic outcome modeling improves base editing variant effect quantification

This paper improves variant effect quantification in base editing screens by integrating genotypic and phenotypic data using a Bayesian network called BEAN.

Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results

This paper introduces the shortest reactional distance (SRD) metric to improve the biological interpretation of metabolite genome-wide association study (mGWAS) results by linking genes to metabolites based on metabolic pathway knowledge.

Association analyses of predicted loss-of-function variants prioritized 15 genes as blood pressure regulators

The paper identifies 15 genes associated with blood pressure regulation by analyzing loss-of-function variants in a large exome sequencing dataset.

Systematic elucidation of genetic mechanisms underlying cholesterol uptake

This study identifies 21 genes whose rare variants affect LDL-C levels by altering cholesterol uptake, using CRISPR screening and co-essentiality analysis.

CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions

The paper assesses the impact of CRISPR perturbations on vascular endothelial cell functions at CAD loci, identifying variants that significantly affect endothelial phenotypes.

Major cell-types in multiomic single-nucleus datasets impact statistical modeling of links between regulatory sequences and target genes

The paper identifies limitations in current methods for inferring regulatory links between cCREs and genes in multiomic data, showing that cell-type-specific correlations affect null distributions and power.

Variation and impact of polygenic hematological traits in monogenic sickle cell disease

The paper evaluates polygenic trait scores for hematological traits in sickle cell disease patients, finding limited predictive power for complications but significant associations for fetal hemoglobin.

Transcriptome-wide association study in UK Biobank Europeans identifies associations with blood cell traits.

This study identifies 557 new gene-trait associations for hematological traits using transcriptome-wide association analysis in UK Biobank data.

From GWAS Variant to Function: a Study of ~148,000 Variants for Blood Cell Traits.

This study prioritizes functional elements of ~148,000 GWAS variants for blood cell traits using a web tool, showing prioritized variants are more likely to be experimentally validated.

Transcriptomic profiling of atrial fibrillation canine models at disease onset

This study profiles transcriptomic changes in canine atrial fibrillation models at disease onset, identifying novel genes and pathways involved in AF pathophysiology.

find-tfbs: a tool to identify functional non-coding variants associated with complex human traits using open chromatin maps and phased whole-genome sequences

Causal role of L-glutamine in sickle cell disease painful crises: a Mendelian randomization analysis

The paper uses Mendelian randomization to confirm a causal link between L-glutamine levels and reduced painful crises in sickle cell disease, while finding no significant causal relationships for other metabolites.

Pleiotropic effects for Parkin and LRRK2 in leprosy type-1 reactions and Parkinson’s disease

The paper identifies rare variants in PRKN and LRRK2 associated with leprosy type-1 reactions and finds overlap with Parkinson’s disease pathogenic mechanisms.

Validation of genome-wide polygenic risk scores for coronary artery disease in French Canadians

This study validates two genome-wide polygenic risk scores for coronary artery disease in French Canadians, showing good performance for prevalent CAD but limited utility for incident and recurrent CAD.

Exome chip meta-analysis elucidates the genetic architecture of rare coding variants in smoking and drinking behavior

The paper analyzes rare coding variants in smoking and drinking behavior using exome chip data, finding that they contribute to phenotypic variation but require larger samples for individual variant associations.