Jacob C. Ulirsch

Host control and regulation of human anellovirus persistence

This study identifies host factors and cellular contexts governing anellovirus persistence through genomic, transcriptomic, and functional analyses.

Functional dissection of complex and molecular trait variants at single nucleotide resolution

This study functionally characterizes 221,412 trait-associated variants using MPRA in 5 cell types, identifying 12,025 regulatory variants and revealing widespread epistasis and non-TF mechanisms.

Flexibly Modeling Rare Variant Pathogenicity Improves Gene Discovery for Complex Traits

FlexRV improves gene discovery for complex traits by modeling nonlinear relationships between variant annotations and phenotypes, outperforming existing methods in association detection and replication.

A consensus variant-to-function score to functionally prioritize variants for disease

This paper introduces a consensus variant-to-function score to prioritize disease-causing variants, showing improved performance in heritability enrichment and fine-mapping.

Simplifying causal gene identification in GWAS loci

This paper introduces CALDERA, a gene prioritization tool for GWAS loci that outperforms existing methods in identifying causal genes.

Improving fine-mapping by modeling infinitesimal effects

This paper introduces improved fine-mapping methods that model infinitesimal effects, showing better calibration and increased PRS accuracy for causal variant identification in complex traits.

An encyclopedia of enhancer-gene regulatory interactions in the human genome

ENCODE-rE2G, a classifier trained on K562 CRISPR perturbations, maps 13,455,443 enhancer-gene interactions across 352 biosamples, matching or exceeding prior models on CRISPR, eQTL, and GWAS benchmarks.

Systematic visualisation of molecular QTLs reveals variant mechanisms at GWAS loci

The paper visualises molecular QTLs to better understand genetic effects on gene expression and identifies causal genes at GWAS loci.

RNA Polymerase II pausing temporally coordinates cell cycle progression and erythroid differentiation

This study shows that SUPT5H mutations disrupt RNA polymerase II pausing, delaying erythroid differentiation and cell cycle progression in human cells.

Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases

The paper introduces a method to prioritize causal genes for complex traits by integrating GWAS data with gene expression and biological data, achieving high precision in gene-trait pair identification.

Rare penetrant mutations confer severe risk of common diseases

The paper identifies rare variant polygenic risk scores as more effective than common variant polygenic risk scores in identifying individuals with outlier phenotypes in common human diseases and complex traits.

Codon affinity in mitochondrial DNA shapes evolutionary and somatic fitness

The paper identifies a synonymous mtDNA variant that affects codon-anticodon affinity and shows its impact on cellular fitness in immune cells.

A cross-disorder dosage sensitivity map of the human genome

This study identifies 114 genome-wide significant rare CNV-disease associations across 30 neurological disorders, revealing 38 novel triplosensitive genes and developing a model to predict dosage sensitivity.

Insights from complex trait fine-mapping across diverse populations

Fine-mapping 148 complex traits in three biobanks with combined n = 811,261 yields 4,518 causal variant-trait pairs, 285 of them repeating in more than one population.

Genome-wide functional screen of 3'UTR variants uncovers causal variants for human disease and evolution

The paper identifies causal 3'UTR variants linked to human disease and evolution using a new high-throughput assay and functional analysis.

Leveraging supervised learning for functionally-informed fine-mapping of cis-eQTLs identifies an additional 20,913 putative causal eQTLs

The paper uses supervised learning to fine-map cis-eQTLs, identifying 20,913 additional putative causal eQTLs and 310 candidate genes.

Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.

A coronary artery disease GWAS of 181,522 cases among 1,165,690 participants yields 241 associations (54 new); an eight-predictor consensus nominates 185 candidate causal genes, 94 with ≥3 predictors.

Tractor: A framework allowing for improved inclusion of admixed individuals in large-scale association studies.

Tractor improves GWAS power and resolution by including admixed individuals through local ancestry-aware analysis.

Functionally-informed fine-mapping and polygenic localization of complex trait heritability

This paper introduces PolyFun, a method that improves fine-mapping accuracy by integrating genome-wide functional data, leading to more causal variant identifications and polygenic localization of trait heritability.

Genome-wide maps of enhancer regulation connect risk variants to disease genes

The paper uses the ABC Model to map enhancer-gene regulation across 131 cell types and tissues, linking GWAS variants to disease genes, particularly in IBD.

HCR-FlowFISH: A flexible CRISPR screening method to identify cis-regulatory elements and their target genes

HCR-FlowFISH identifies cis-regulatory elements and their target genes by quantifying gene expression changes after CRISPR perturbations, using >270,000 perturbations to detect CREs for multiple genes.

Gene-centric functional dissection of human genetic variation uncovers regulators of hematopoiesis

The paper performs a pooled loss-of-function screen in hematopoietic cells to identify genes underlying GWAS loci associated with red blood cell traits, finding 77 genes at 38 loci with biological relevance.

Interrogation of human hematopoiesis at single-cell and single-variant resolution

This study fine-maps genetic variants associated with blood cell traits and identifies cell types and causal mechanisms using single-cell chromatin accessibility data from the UK Biobank.

Genetic predisposition to mosaic Y chromosome loss in blood is associated with genomic instability in other tissues and susceptibility to non-haematological cancers

The paper identifies genetic determinants of mosaic Y chromosome loss in blood and links it to genomic instability and non-haematological cancer risk.

The Genetic Landscape of Diamond-Blackfan Anemia

This study identifies genetic mutations in 78% of Diamond-Blackfan anemia patients using whole exome sequencing, finds new RP genes, and reports genotype-phenotype associations.

Iron and Heme Coordinate Erythropoiesis through HRI-Mediated Regulation of Protein Translation and Gene Expression

The paper investigates how iron, heme, and HRI regulate protein translation and gene expression in erythroblasts during iron deficiency, identifying novel pathways and regulators of erythropoiesis.

Detecting genome-wide directional effects of transcription factor binding on polygenic disease risk

The paper introduces a method to detect directional effects of transcription factor binding on disease risk using GWAS data and applies it to identify new causal genes and mechanisms.