Ryan Tewhey

Atlas of HIV cis-regulatory elements reveals extensive transcriptional variation across clades, isolates, and within individuals

The paper creates a regulatory atlas of HIV-1 and HIV-2 by analyzing transcriptional variation across clades, isolates, and individuals using MPRAs and predictive models.

Position-dependent variant effects reveal importance of context in genomic regulation

This study shows that variant position within MPRAs affects regulatory activity, revealing positional bias in variant effect size estimation.

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.

Systematic functional dissection of germline noncoding risk variants impacting clonal hematopoiesis

The paper identifies non-coding variants associated with clonal hematopoiesis and demonstrates their regulatory impact on gene expression and clonal expansion.

Linking candidate causal autoimmune variants to T cell networks using genetic and epigenetic screens in primary human T cells.

The paper identifies 545 expression-modulating variants in CD4+ T cells linked to autoimmune diseases and shows they regulate genes in a lymphocyte activation network.

Global cis-regulatory landscape of double-stranded DNA viruses

The paper identifies ~2,000 cis-regulatory elements (CREs) across 27 dsDNA viruses using reporter assays and machine learning, revealing their regulatory features and associated transcription factors.

Expanding the DNA Motif Lexicon of the Transcriptional Regulatory Code

The paper expands the DNA motif lexicon of transcriptional regulatory code by identifying composite elements and using a deep learning model to predict their activity and impact of variants.

GAME: Genomic API for Model Evaluation

GAME provides a standardized framework for benchmarking genomics models across tasks, enabling consistent evaluation and community contributions.

Identifying non-coding variant effects at scale via machine learning models of cis-regulatory reporter assays

This study introduces MPAC, a machine learning model that predicts the cis-regulatory impact of non-coding variants, demonstrating its accuracy across diverse applications and datasets.

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.

Machine-guided design of synthetic cell type-specific cis-regulatory elements

This paper designs synthetic cis-regulatory elements (CREs) that outperform natural ones in driving cell type-specific gene expression using deep learning and experimental validation.

Three linked opposing regulatory variants under selection associate with IVD

The paper identifies three regulatory variants associated with IVD expression and linked to GWAS signals, showing synergistic and opposing effects through functional experiments.

Multi-center integrated analysis of non-coding CRISPR screens

The paper reports 109 non-coding CRISPR screens analyzing 13.3Mb of the genome, identifies CRE-gene links, and provides guidelines and tools for screening non-coding regulatory elements.

Whole genome functional characterization of RE1 silencers using a modified massively parallel reporter assay

The paper identifies 1,500 human variants affecting RE1 silencers using a modified MPRA assay and shows how REST binding motifs influence silencing.

Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells

The paper identifies causal genetic variants in autoimmune diseases by combining allele-specific reporter assays with chromatin accessibility data, showing their impact on gene expression and T cell function.

A Systematic Strategy for Identifying Causal Single Nucleotide Polymorphisms and Their Target Genes on Juvenile Arthritis Risk Haplotypes

This paper identifies causal SNPs and their target genes in JIA risk haplotypes using MPRA and CRISPRi, finding 84 SNPs that alter gene expression and regulate multiple genes in TRAF1 and LNPEP/ERAP2 loci.

CoRE-ATAC: A deep learning model for the functional classification of regulatory elements from single cell and bulk ATAC-seq data

CoRE-ATAC is a deep learning model that classifies regulatory elements from ATAC-seq data, accurately predicting cis-RE functions across multiple cell types and identifying cell-specific variations in regulatory activity.

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.

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.

Functional characterization of thousands of type 2 diabetes-associated and chromatin-modulating variants under steady state and endoplasmic reticulum stress

The paper identifies functional β cell transcriptional variants from T2D GWAS SNPs using MPRA, showing strong correlation with chromatin accessibility and revealing regulatory features under stress conditions.

Genome-wide regulatory model from MPRA data predicts functional regions, eQTLs, and GWAS hits

The paper trains a machine learning model on MPRA data to predict regulatory activity, eQTLs, and GWAS hits across the genome.