A5091650582- Genetic Associations and Epidemiology
- Cancer Genomics and Diagnostics
- Ethics in Clinical Research
- Genomics and Rare Diseases
- Prostate Cancer Treatment and Research
- Single-cell and spatial transcriptomics
- Cancer-related molecular mechanisms research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- RNA Research and Splicing
- Genetic factors in colorectal cancer
- Genetic Mapping and Diversity in Plants and Animals
- Bioinformatics and Genomic Networks
- BRCA gene mutations in cancer
- COVID-19 Clinical Research Studies
- Genomics and Phylogenetic Studies
- Prostate Cancer Diagnosis and Treatment
- Long-Term Effects of COVID-19
- Cancer-related gene regulation
- Extracellular vesicles in disease
- Gene expression and cancer classification
- COVID-19 and healthcare impacts
- COVID-19 and Mental Health
- RNA modifications and cancer
University of California, Los Angeles
2019-2025
Abstract Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as grade. To interrogate the evolutionary origins cancer heterogeneity, we analyzed 666 whole genomes. We identified a compendium 223 recurrently mutated driver regions, influencing downstream processes gene expression. validated individual germline variants that predispose tumors to acquire specific...
Summary With the continuing coronavirus disease 2019 (COVID-19) pandemic coupled with phased reopening, it is critical to identify risk factors associated susceptibility and severity of in a diverse population help shape government policies, guide clinical decision making, prioritize future COVID-19 research. In this retrospective case-control study, we used de-identified electronic health records (EHR) from University California Los Angeles (UCLA) Health System between March 9 th , 2020...
Single-cell RNA-sequencing (scRNA-Seq) is a compelling approach to directly and simultaneously measure cellular composition state, which can otherwise only be estimated by applying deconvolution methods bulk RNA-Seq estimates. However, it has not yet become widely used tool in population-scale analyses, due its prohibitively high cost. Here we show that given the same budget, statistical power of cell-type-specific expression quantitative trait loci (eQTL) mapping increased through...
Abstract Background Large medical centers in urban areas, like Los Angeles, care for a diverse patient population and offer the potential to study interplay between genetic ancestry social determinants of health. Here, we explore implications within University California, Angeles (UCLA) ATLAS Community Health Initiative—an ancestrally biobank genomic data linked with de-identified electronic health records (EHRs) UCLA patients ( N =36,736). Methods We quantify extensive continental...
Coronavirus disease 2019 (COVID-19) has exposed health care disparities in minority groups including Hispanics/Latinxs (HL). Studies of COVID-19 risk factors for HL have relied on county-level data. We investigated using individual-level, electronic records a Los Angeles system between March 9, 2020, and August 31, 2020. Of 9,287 tested SARS-CoV-2, 562 were positive. constituted an increasing percentage all positive individuals as severity escalated. Multiple identified Non-Hispanic/Latinx...
Abstract Large medical centers located in urban areas such as Los Angeles care for a diverse patient population and offer the potential to study interplay between genomic ancestry social determinants of health within single system. Here, we introduce UCLA ATLAS Community Health Initiative – biobank data linked with de-identified electronic records (EHRs) patients. We leverage unique diversity explore self-reported race/ethnicity genetic disease context using phenotypes extracted from EHR....
<h2>Summary</h2> Genome-wide association studies (GWASs) have uncovered susceptibility loci associated with psychiatric disorders such as bipolar disorder (BP) and schizophrenia (SCZ). However, most of these are in non-coding regions the genome, causal mechanisms link between genetic variation disease risk is unknown. Expression quantitative trait locus (eQTL) analysis bulk tissue a common approach used for deciphering underlying mechanisms, although this can obscure cell-type-specific...
Mapping genetic variants that regulate gene expression (eQTL mapping) in large-scale RNA sequencing (RNA-seq) studies is often employed to understand functional consequences of regulatory variants. However, the high cost RNA-seq limits sample size, depth, and, therefore, discovery power eQTL studies. In this work, we demonstrate that, given a fixed budget, can be increased by lowering depth per and increasing number individuals sequenced assay. We perform whole-blood tissue across 1,490 at...
Abstract The vast majority of disease-associated single nucleotide polymorphisms (SNP) identified from genome-wide association studies (GWAS) are localized in non-coding regions. A significant fraction these variants impact transcription factors binding to enhancer elements and alter gene expression. To functionally interrogate the activity such we developed snpSTARRseq, a high-throughput experimental method that can functional hundreds thousands on activity. snpSTARRseq dramatically...
Abstract Single-cell RNA-sequencing (scRNA-Seq) is a compelling approach to simultaneously measure cellular composition and state which impossible with bulk profiling approaches. However, it has not yet become widely used tool in population-scale analyses, due its prohibitively high cost. Here we show that given the same budget, statistical power of cell-type-specific expression quantitative trait loci (eQTL) mapping can be increased through low-coverage per-cell sequencing more samples...
Abstract Genome-wide association studies (GWAS) have identified more than 140 prostate cancer (PrCa) risk regions which provide potential insights into causal mechanisms. Multiple lines of evidence show that a significant proportion PrCa can be explained by germline variants dysregulate nearby target genes in prostate-relevant tissues thus altering disease risk. The traditional approach to explore this hypothesis has been correlating GWAS with steady-state transcript levels, referred as...
Genetic predisposition for complex traits often acts through multiple tissues at different time points during development. As a simple example, the genetic obesity could be manifested either inherited variants that control metabolism regulation of genes expressed in brain, or fat storage dysregulation adipose tissue, both. Here we describe statistical approach leverages tissue-specific expression quantitative trait loci (eQTLs) corresponding to prioritize relevant tissue underlying given...
Abstract Methods that link genetic variation to steady-state gene expression levels, such as quantitative trait loci (eQTLs), are widely used functionally annotate trait-associated variants, but they limited in identifying context-dependent effects on transcription. To address this challenge, we developed the cistrome-wide association study (CWAS), a framework for nominating variants impact traits through their chromatin state. CWAS associates determinants of cistromes ( e.g. , genome-wide...
Abstract Genetic predisposition for complex traits often acts through multiple tissues at different time points during development. As a simple example, the genetic obesity could be manifested either inherited variants that control metabolism regulation of genes expressed in brain, or fat storage dysregulation adipose tissue, both. Here we describe statistical approach leverages tissue-specific expression quantitative trait loci (eQTLs) corresponding to prioritize relevant tissue underlying...
Abstract Genome-wide association studies (GWAS) have uncovered susceptibility loci associated with psychiatric disorders like bipolar disorder (BP) and schizophrenia (SCZ). However, most of these are in non-coding regions the genome unknown causal mechanisms link between genetic variation disease risk. Expression quantitative trait (eQTL) analysis bulk tissue is a common approach to decipher underlying mechanisms, though this can obscure cell-type specific signals thus masking trait-relevant...
Abstract Methods that link genetic variation to steady-state gene expression levels, such as quantitative trait loci (eQTLs), are widely used functionally annotate trait-associated variants, but they limited in identifying context-dependent effects on transcription. To address this challenge, we developed the cistrome-wide association study (CWAS), a framework for nominating variants impact traits through their chromatin state. CWAS associates determinants of cistromes (e.g., genome-wide...
ABSTRACT Mapping genetic variants that regulate gene expression (eQTL mapping) in large-scale RNA sequencing (RNA-seq) studies is often employed to understand functional consequences of regulatory variants. However, the high cost RNA-Seq limits sample size, depth, and therefore, discovery power. In this work, we demonstrate that, given a fixed budget, eQTL power can be increased by lowering depth per increasing number individuals sequenced assay. We perform whole blood tissue across 1490 at...
ABSTRACT Genome-wide association studies (GWAS) have identified numerous genetic loci associated with breast and prostate cancer risk, suggesting that germline dysregulation influences tumorigenesis. However, the biological function underlying many associations is not well-understood. Previous efforts to annotate focused on protein-coding genes (pcGenes) largely ignore non-coding RNAs (ncRNAs) which account for most transcriptional output in human cells can regulate transcription of both...
Abstract The vast majority of disease-associated single nucleotide polymorphisms identified from genome-wide association study (GWAS) are localized in non-coding regions. A significant fraction these variants impact transcription factors binding to enhancer elements and alter gene expression. To functionally interrogate the activity such we developed snpSTARRseq, a high-throughput experimental method that can functional hundreds thousands on activity. snpSTARRseq dramatically improves...