Benjamin Gläser

The paper analyzes over 800,000 human genomes to assess penetrance of clinically relevant variants, finding that 95% of pLoF variants in severe diseases have explanations for lack of disease manifestation.

The paper constructs a single-cell multiomics atlas of the human pancreas across development, health, and T2D, identifying plastic cell states and lineage trajectories.

The paper shows that DNA methylation changes at clustered CpG sites encode chronological age with high accuracy using deep learning on blood samples.

The paper creates a comprehensive atlas of allele-specific DNA methylation across 39 human cell types, identifying 325k genomic regions and 460 novel imprinted loci with cell-type-specific patterns.

This study identifies G6PC2's role in regulating glucagon secretion in α-cells, showing it controls glucose setpoint and suggests G6PC2 inhibitors could improve glycemic control.

This paper develops a probabilistic model for cell type deconvolution using single-molecule DNA methylation haplotypes, showing improved accuracy in detecting rare cell types.

Rare-variant depletion in 1kb windows of 76,156 gnomAD genomes, versus feature-adjusted mutation expectations, marks regulatory elements and outperforms seven alternative scores at flagging functional non-coding variants.

The paper develops a method to infer compound heterozygosity from exome sequencing data, achieving high accuracy in phasing rare variants for recessive disease diagnosis.

The paper introduces GP-age, a DNA methylation-based age prediction model using 30 CpG sites and a cohort-based machine learning approach, achieving high accuracy on both array and sequencing data.

The paper constructs a human DNA methylation atlas using whole-genome bisulfite sequencing of 39 cell types, revealing cell type-specific methylation patterns and regulatory elements.

The paper identifies megakaryocytes and erythroblasts as major contributors to circulating cell-free DNA (cfDNA) and shows their DNA can serve as biomarkers for blood cell production disorders.

The paper identifies ten new genes with coding variants linked to Crohn's disease risk using sequencing data from over 30,000 patients and 80,000 controls.

This study identifies 35 genes associated with circulating lipid levels using rare coding variants from 170,000 exomes across multiple ancestries.

The paper uses immune cell type-specific methylation patterns in circulating cell-free DNA to monitor immune dynamics and find that immune-derived cfDNA levels reflect immune homeostasis and predict immune responses to perturbations.

The paper evaluates penetrance and variable expressivity of monogenic metabolic conditions using exome data from 77,184 individuals, finding that monogenic variants have larger effect sizes than polygenic scores but low penetrance.

The paper introduces cfChIP-seq to analyze cell-free nucleosomes and shows it can detect disease-related transcriptional changes and patient-specific features in cancer.

The paper evaluates potential drug targets using loss-of-function genetic variants from gnomAD, highlighting the importance of deep curation and targeted recall studies for drug discovery.

From 125,748 exomes and 15,708 genomes, 443,769 high-confidence predicted loss-of-function variants yield LOEUF, a continuous gene intolerance score tracking mouse lethality, cell essentiality, and disease associations.

The paper develops an expression-based annotation metric to improve rare variant interpretation by filtering false-positive loss-of-function variants and identifying pathogenic variants in highly expressed exons.

The paper analyzes loss-of-function variants in LRRK2 across large genomic datasets to assess the safety of partial LRRK2 inhibition as a Parkinson's disease therapy.

The paper analyzes multi-nucleotide variants (MNVs) in 125,748 exomes and 15,708 genomes, identifying their distribution, mutational origins, and functional implications.

The paper develops a method to determine the tissue origins of circulating cell-free DNA using a methylation atlas and validates it in healthy and disease states.

The paper identifies methylation patterns specific to intestinal epithelial cells to detect cell-free DNA in plasma, showing increased levels in advanced CRC compared to IBD and PDAC.

This study identifies rare genetic variants associated with type 2 diabetes using exome sequencing of 20,791 cases and 24,440 controls, and provides a Bayesian framework to improve variant prioritization.

This paper clusters T2D genetic loci using multi-trait associations to identify disease mechanisms and subtypes, finding distinct clinical outcomes linked to each cluster.