A5028223846- Genetic Associations and Epidemiology
- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- RNA and protein synthesis mechanisms
- vaccines and immunoinformatics approaches
- Tuberculosis Research and Epidemiology
- Chronic Lymphocytic Leukemia Research
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Atherosclerosis and Cardiovascular Diseases
- Monoclonal and Polyclonal Antibodies Research
- Molecular Biology Techniques and Applications
- Cell Image Analysis Techniques
- Systemic Sclerosis and Related Diseases
- Genetic factors in colorectal cancer
- interferon and immune responses
- Genomics and Rare Diseases
- Celiac Disease Research and Management
University of California, San Diego
2023-2025
Harvard University
2017-2024
Center for Systems Biology
2018-2024
Broad Institute
2017-2023
Brigham and Women's Hospital
2017-2022
Harvard University Press
2018
Mass General Brigham
2017
École Polytechnique Fédérale de Lausanne
2016
Recent improvements in quantitative proteomics approaches, including Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS), permit reproducible large-scale protein measurements across diverse cohorts. Together with genomics, transcriptomics, and other technologies, transomic data sets can be generated that detailed analyses broad molecular interaction networks. Here, we examine mitochondrial links to liver metabolism through the genome, transcriptome, proteome, metabolome...
Abstract Many diseases exhibit population-specific causal effect sizes with trans-ethnic genetic correlations significantly less than 1, limiting polygenic risk prediction. We develop a new method, S-LDXR, for stratifying squared correlation across genomic annotations, and apply S-LDXR to genome-wide summary statistics 31 complex traits in East Asians (average N = 90K) Europeans 267K) an average of 0.85. determine that is 0.82× (s.e. 0.01) depleted the top quintile background selection...
Abstract The morphology of cells is dynamic and mediated by genetic environmental factors. Characterizing how variation impacts cell can provide an important link between disease association cellular function. Here, we combine genomic sequencing high-content imaging approaches on iPSCs from 297 unique donors to investigate the relationship variants map what term morphological quantitative trait loci (cmQTLs). We identify novel associations rare protein altering in WASF2 , TSPAN15 PRLR with...
Abstract Of the 1.8 billion people worldwide infected with Mycobacterium tuberculosis , 5–15% will develop active (TB). Approximately half progress to TB within first 18 months after infection, presumably because they fail mount an effective initial immune response. Here, in a genome-wide genetic study of early progression, we genotype 4002 cases and their household contacts Peru. We quantify heritability ( $${\it{h}}_{\it{g}}^2$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML">...
Recent studies have highlighted the role of gene networks in disease biology. To formally assess this, we constructed a broad set pathway, network, and pathway+network annotations applied stratified LD score regression to 42 diseases complex traits (average N = 323K) identify enriched annotations. First, analyzed 18,119 biological pathways. We identified 156 pathway-trait pairs whose enrichment was statistically significant (FDR < 5%) after conditioning on all genes 75 known functional (from...
Despite significant progress in annotating the genome with experimental methods, much of regulatory noncoding remains poorly defined. Here we assert that elements may be characterized by leveraging local epigenomic signatures where specific transcription factors (TFs) are bound. To link these two features, introduce IMPACT, a annotation strategy identifies defined cell-state-specific TF binding profiles, learned from 515 chromatin and sequence annotations. We validate IMPACT using multiple...
Cytokines are critical to human disease and attractive therapeutic targets given their widespread influence on gene regulation transcription. Defining the downstream regulatory mechanisms influenced by cytokines is central defining drug mechanisms. One promising strategy use interactions between expression quantitative trait loci (eQTLs) cytokine levels define target genes
Regulatory variation plays a major role in complex disease and that cell type-specific binding of transcription factors (TF) is critical to gene regulation. However, assessing the contribution genetic TF-binding sites heritability challenging, as often annotations from directly measured TF are not currently available for most type-TF pairs. We investigate approaches annotate binding, including chromatin data sequence-based predictions. find constructed by intersecting predictions with...
Abstract The morphology of cells is dynamic and mediated by genetic environmental factors. Characterizing how variation impacts cell can provide an important link between disease association cellular function. Here, we combined genomic high-content imaging approaches on iPSCs from 297 unique donors to investigate the relationship variants map what term morphological quantitative trait loci (cmQTLs). We identified novel associations rare protein altering in WASF2, TSPAN15 , PRLR with several...
Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of cellular heterogeneity by providing gene expression data at single-cell resolution, uncovering insights into rare cell populations, cell-cell interactions, and regulation. Foundation models pretrained on large-scale scRNA-seq datasets have shown great promise in analyzing such data, but existing approaches are often limited to modeling a small subset highly expressed genes lack integration external genespecific knowledge....
Significance The anti-HIV drug KP1212 was designed to intentionally increase the mutation rate of HIV, thereby causing viral population collapse. Its mutagenicity and thus antiviral activity proposed be result tautomerization. We used 2D IR spectroscopy identify rapidly interconverting tautomers under physiological conditions. traditionally rare enol–imino tautomer for nucleobases found major species KP1212, providing a structural support hypothesis. further that is significantly protonated...
Abstract Trans-ancestry genetic research promises to improve power detect signals, fine-mapping resolution, and performances of polygenic risk score (PRS). We here present a large-scale genome-wide association study (GWAS) rheumatoid arthritis (RA) which includes 276,020 samples five ancestral groups. conducted trans-ancestry meta-analysis identified 124 loci ( P < 5 × 10 -8 ), 34 were novel. Candidate genes at the novel suggested essential roles immune system (e.g., TNIP2 TNFRSF11A )...
Abstract Human height can be divided into sitting and leg length, reflecting growth of different parts the skeleton whose relative proportions are captured by ratio to total (as ratio, SHR). Height is a highly heritable trait, its genetic basis has been well-studied. However, determinants skeletal proportion much less well-characterized. Expanding substantially on past work, we performed genome-wide association study (GWAS) SHR in ∼450,000 individuals with European ancestry ∼100,000 East...
Abstract Heritable diseases often manifest in a highly tissue-specific manner, with different disease loci mediated by genes distinct tissues or cell types. We propose Tissue-Gene Fine-Mapping (TGFM), fine-mapping method that infers the posterior probability (PIP) for each gene-tissue pair to mediate locus analyzing GWAS summary statistics (and in-sample LD) and leveraging eQTL data from diverse build cis-predicted expression models; TGFM also assigns PIPs causal variants are not gene...