Alexander Gusev

Deep transcriptomic analysis of molecular mediators of complex traits in heterogeneous stock (HS) rats

This paper expands the RatGTEx resource with transcriptome-wide associations across 3,160 RNA-seq samples, identifying 7,473 gene-trait links and 144,876 QTLs for 22,599 genes.

Data-driven RNA phenotyping captures genetically regulated dimensions of the transcriptome

LaDDR improves xQTL and GWAS discovery by generating latent RNA phenotypes without requiring complete gene annotations, outperforming existing knowledge-driven methods in multiple tissues.

Meta-Analysis of Rare Cancers Leveraging Clinically Ascertained Cohorts Reveals Novel Germline Susceptibility Loci

This study performs GWAS on 20 rare cancers using three cohorts, identifying nine novel susceptibility loci with replication across eight cancer types.

Breaking the sparsity barrier in clinical targeted-panel sequencing: Mapping the inherited determinants of mutational signatures

This paper introduces GroupSig, a framework to overcome sparsity in clinical targeted-panel sequencing data, identifying inherited determinants of mutational signatures in cancer.

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.

A time-to-event heritability framework for inferring the genetic architecture of longitudinal traits

This paper introduces COXMM, a model for estimating heritability of time-to-event traits, showing it outperforms non-TTE methods and reveals heritability patterns in longitudinal data.

Integrating perturbational screens, eQTL, and GWAS data identifies mediating genes for complex traits

The paper integrates perturbational screens, eQTL, and GWAS data to identify mediating genes for complex traits, finding 546 significant genes enriched for immune response and cellular signaling.

Cancers modulate p53 truncal neoantigen display to evade T cell detection

This study identifies that cancers limit p53 neoantigen display on MHC molecules, evading T cell detection through immune selection and ERAP1-mediated destruction.

Circulating chromatin reveals the effects of disease-associated variants on gene regulation

The paper identifies cell-free chromatin QTLs (cfcQTLs) from cancer patients' blood to uncover regulatory effects of genetic variants across diverse tissues and diseases.

Discovery of disease-associated cellular states using ResidPCA in single-cell RNA and ATAC sequencing data

The paper introduces ResidPCA, a method for identifying cell states in single-cell RNA and ATAC sequencing data, showing improved accuracy over existing methods in both simulated and real datasets.

Limited overlap between genetic effects on disease susceptibility and disease survival

The paper compares genetic effects on disease susceptibility and progression, finding limited overlap and suggesting larger samples or different progression measures are needed.

Polygenic modifiers of expressivity in telomere biology disorders

This study identifies polygenic modifiers of expressivity in telomere biology disorders by showing how common and rare genetic variants interact to influence clinical variability.

Clinico-genomic features predict distinct metastatic phenotypes in cutaneous melanoma

This study identifies distinct metastatic phenotypes in cutaneous melanoma using clinico-genomic data and machine learning, linking specific mutations and clinical factors to organ-specific metastasis.

Rare germline structural variants increase risk for pediatric solid tumors

This study identifies rare germline structural variants as risk factors for pediatric solid tumors, particularly neuroblastoma, by analyzing genome sequencing data from affected children and controls.

Multimodal analysis of RNA sequencing data powers discovery of complex trait genetics

The paper introduces Pantry, a framework for generating diverse RNA phenotypes from RNA-seq data and integrating them with genetic data, leading to increased gene-trait association discoveries.

Aladynoulli: A Bayesian approach to disease progression modeling for genomic discovery and clinical prediction

ALADYNOULLI integrates longitudinal health records and genetic data to model disease progression, identifying interpretable disease signatures with cross-population consistency and improving clinical prediction.

Improved multi-ancestry fine-mapping identifies cis-regulatory variants underlying molecular traits and disease risk

The paper introduces SuShiE, a model that improves multi-ancestry fine-mapping of cis-molQTLs, identifying more genes and prioritizing functionally enriched variants.

The lingering effects of Neanderthal introgression on human complex traits

This study assesses the contribution of Neanderthal introgression to human complex traits using UK Biobank data, finding significant but depleted effects compared to modern human variants.

Cross-ancestry, cell-type-informed atlas of gene, isoform, and splicing regulation in the developing human brain

The paper constructs a cross-ancestry, cell-type-informed gene regulatory atlas of the developing human brain, identifying genetic regulation and linking it to neuropsychiatric disorders.

Compressed Perturb-seq: highly efficient screens for regulatory circuits using random composite perturbations

Compressed Perturb-seq reduces cost and complexity of CRISPR screens by using random composite perturbations and computational decomposition, achieving similar accuracy to conventional methods with greater power to detect genetic interactions.

Utilizing Electronic Health Records (EHR) and Tumor Panel Sequencing to Demystify Prognosis of Cancer of Unknown Primary (CUP) patients

This paper develops OncoNPC, a machine learning classifier for CUP patients using tumor sequencing data, showing improved survival outcomes with treatment aligned to predicted cancer types.

Optimized high-throughput screening of non-coding variants identified from genome-wide association studies

This study develops snpSTARRseq, a high-throughput method to test non-coding variants from GWAS, showing 37% of prostate cancer risk loci alter enhancer activity.

Polygenic Prediction of Molecular Traits using Large-Scale Meta-analysis Summary Statistics

The paper develops TWAS models using eQTL summary statistics to predict gene expression and identifies novel schizophrenia associations.

The regulatory landscape of multiple brain regions in outbred heterogeneous stock rats

The paper identifies cis-QTLs and eQTLs in HS rats across five brain regions, finds colocalization with human GWAS results, and shows higher eQTL density compared to human data.

Multi-context genetic modeling of transcriptional regulation resolves novel disease loci

The paper introduces CONTENT, a method for multi-context genetic modeling of transcriptional regulation, which improves power and discovers more gene-phenotype associations in TWAS.

Genetic determinants of chromatin reveal prostate cancer risk mediated by context-dependent gene regulation

The paper introduces CWAS, a method linking genetic variation to chromatin states, identifying novel prostate cancer risk loci and regulatory mechanisms not detectable by eQTLs.

Germline cancer gene expression quantitative trait loci influence local and global tumor mutations

The paper identifies germline variants that influence somatic mutations in cancer genes through expression regulation across multiple cancer types.

Multi-ancestry fine-mapping improves precision to identify causal genes in transcriptome-wide association studies

This paper introduces MA-FOCUS, a multi-ancestry fine-mapping framework that improves the identification of causal genes in TWAS by leveraging ancestry-specific LD and eQTL patterns.

Germline predisposition to pediatric Ewing sarcoma is uniquely characterized by inherited pathogenic variants in DNA damage repair genes

This study identifies inherited pathogenic variants in DNA damage repair genes as a distinct germline risk factor for Ewing sarcoma, with FANCC showing significant enrichment.

Germline variants associated with immunotherapy-related adverse events

This study identifies three germline variants associated with immune-related adverse events in patients treated with immune checkpoint inhibitors.