Jean‐Laurent Casanova

Mechanistic 5'UTR Variant Scoring Expands Rare Variant Discovery in the UK Biobank

The paper introduces 5ULTRA, a machine-learning tool for annotating 5'UTR variants, identifying new gene-phenotype associations in the UK Biobank that are missed by existing methods.

Humans homozygous for rare or common hypomorphic IL23R variants are prone to tuberculosis

Homozygosity for hypomorphic IL23R variants (G149R, G300V, R381Q) partly impairs IL-23-dependent IFN-γ production in patient cells; with L372F (effect inferred), they are enriched in tuberculosis, not MSMD or CMC patients.

Polyunsaturated fatty acid-derived lipid mediator networks characterize COVID-19 severity and risk for critical illness

The paper identifies lipid mediator networks associated with COVID-19 severity and risk of critical illness using multi-omics profiling across disease severity groups.

Elevated levels of intracellular RNA lariats suppress the antiviral response

The paper shows that accumulation of intracellular RNA lariats in DBR1-null cells reduces antiviral response by desensitizing dsRNA sensors.

A flow cytometry-based assay to quantify the binding of transmembrane ligands to their cognate receptors using fluorescent virus-like particles

This paper introduces a flow cytometry-based assay using fluorescent virus-like particles to quantify transmembrane ligand-receptor binding, showing it can study patient-derived variants and enable single-cell analysis of multiple interactions.

ARAP2 regulates responses to interferon-gamma by restricting SOCS1

This study identifies ARAP2 as a regulator of IFN-gamma signaling by modulating SOCS1 function through a phosphorylation-dependent interaction.

Human iPSC derived alveolar macrophages reveal macrophage subtype specific functions of itaconate in M. tuberculosis host defense

This study investigates itaconate's role in human macrophages, showing distinct effects in alveolar-like and M-CSF-derived macrophages during M. tuberculosis infection.

Mechanism of neurodegeneration mediated by clonal inflammatory microglia

The paper identifies clonal inflammatory microglia as a cause of neurodegeneration in LCH and ECD, showing their association with neuronal loss and suggesting CSF1R inhibitors as a therapeutic option.

A microglia clonal inflammatory disorder in Alzheimer's Disease

The paper identifies microglia-specific somatic clones with pathogenic variants in Alzheimer's Disease patients that drive neuro-inflammation through the MAPK pathway.

A genome-wide arrayed CRISPR screen identifies PLSCR1 as an intrinsic barrier to SARS-CoV-2 entry that recent virus variants have evolved to resist

The paper identifies PLSCR1 as a host factor restricting SARS-CoV-2 entry, which recent variants have evolved to bypass, through a CRISPR screen and integration of genetic studies.

Human Germline Heterozygous Gain-of-Function STAT6 Variants Cause Severe Allergic Disease

This study identifies heterozygous gain-of-function STAT6 variants in two patients with severe allergic disease and shows JAK inhibitors reduce the enhanced STAT6 responses.

Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe

This study uses ancient genomics to show that genetic adaptation to pathogens in post-Neolithic Europe increased inflammatory disease risk through antagonistic pleiotropy.

Environmental and genetic drivers of population differences in SARS-CoV-2 immune responses

The paper identifies environmental and genetic factors influencing population differences in SARS-CoV-2 immune responses using single-cell RNA-sequencing data.

Genome-wide detection of human variants that disrupt intronic branchpoints

The paper introduces BPHunter, a computational tool to detect intronic variants disrupting branchpoints, identifies known and novel mutations, and validates them experimentally.

DPP9 deficiency: an inflammasomopathy which can be rescued by lowering NLRP1/IL-1 signaling

This study identifies DPP9 deficiency as a Mendelian disorder causing inflammasome hyperactivity, which can be rescued by reducing NLRP1/IL-1 signaling in mice.

Deciphering the consequence of deep intronic variants: a progeroid syndrome caused by a TAPT1 mutation is revealed by combined RNA/SI-NET sequencing

The paper identifies a deep intronic TAPT1 mutation causing progeroid syndrome using RNA-seq and homozygosity mapping, showing it leads to exon skipping and protein-null allele.

A common TMPRSS2 variant protects against severe COVID-19

This paper identifies a common TMPRSS2 variant that reduces the risk of severe COVID-19 by impairing SARS-CoV-2 entry into cells.

Heterogeneity of monocyte subsets and susceptibility to influenza virus contribute to inter-population variability of protective immunity

The paper investigates monocyte subset heterogeneity and its impact on influenza virus susceptibility across populations, revealing differences in transcriptional responses and infection resistance between African and European ancestry individuals.

Controlling for Human Population Stratification in Rare Variant Association Studies

This paper evaluates methods to control population stratification in rare variant association studies, finding that a novel permutation method maintains correct type I error across all scenarios.

Taking population stratification into account by local permutations in rare-variant association studies on small samples

This paper introduces LocPerm, a permutation method that accounts for population stratification in rare-variant association studies, showing it maintains type I error control and stable power across small samples and stratification levels.

Loss of C2orf69 defines a fatal auto-inflammatory mitochondriopathy in Humans and Zebrafish

The paper identifies C2orf69 deficiency as a cause of a fatal auto-inflammatory syndrome in humans and zebrafish, affecting mitochondrial function and immune/cNS development.

Detection of homozygous and hemizygous partial exon deletions by whole-exome sequencing

HMZDelFinder_opt improves detection of homozygous and hemizygous partial exon deletions in WES data by optimizing reference controls and using a sliding window approach.

Genome-wide association study of resistance to Mycobacterium tuberculosis infection identifies a locus at 10q26.2 in three distinct populations

Negative selection on human genes causing severe inborn errors depends on disease outcome and both the mode and mechanism of inheritance

The paper develops CoNeS to assess negative selection on genes causing severe inborn errors, finding that disease outcome and inheritance mode/mechanism influence selection strength.

Multi-batch cytometry data integration for optimal immunophenotyping

The paper introduces iMUBAC, a framework for integrating multi-batch cytometry data to identify cell types and detect immunophenotype abnormalities across datasets.

A genome-wide case-only test for the detection of digenic inheritance in human exomes

The paper introduces a genome-wide case-only test to detect digenic inheritance in human exomes, showing it is more powerful than case-control tests and robust to population stratification.

Common homozygosity for predicted loss-of-function variants reveals both redundant and advantageous effects of dispensable human genes

The paper identifies 166 dispensable human genes with common loss-of-function variants that show relaxed selective constraints and some evidence of positive selection.

A toxic palmitoylation on Cdc42 drives a severe autoinflammatory syndrome

The paper identifies a mutation in Cdc42 that causes a severe autoinflammatory syndrome by trapping the protein in the Golgi and disrupting its membrane interaction.

SeqTailor: a user-friendly webserver for the extraction of DNA or protein sequences from next-generation sequencing data

SeqTailor extracts DNA or protein sequences from VCF files for genetic variant analysis, providing a user-friendly webserver to support sequence-based predictions.

Incomplete penetrance for isolated congenital asplenia in humans with mutations in translated and untranslated RPSA exons

The paper reports new RPSA mutations causing isolated congenital asplenia, including 5-UTR mutations and incomplete penetrance in some cases.