A5000094987- RNA modifications and cancer
- Genetic Associations and Epidemiology
- Single-cell and spatial transcriptomics
- Cancer-related molecular mechanisms research
- Liver Disease Diagnosis and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Epigenetics and DNA Methylation
- Adipose Tissue and Metabolism
- Congenital heart defects research
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Lipid metabolism and disorders
- Bioinformatics and Genomic Networks
- Pancreatic function and diabetes
- Nutrition, Genetics, and Disease
- Multilevel Inverters and Converters
- Genomic variations and chromosomal abnormalities
- Extracellular vesicles in disease
- Digestive system and related health
- Rangeland Management and Livestock Ecology
- Cell Image Analysis Techniques
- Lipoproteins and Cardiovascular Health
- Alcohol Consumption and Health Effects
- Genomics and Rare Diseases
University of California, Los Angeles
2017-2024
Princeton University
2022-2023
Mpala Research Center and Wildlife Foundation
2023
University of California, San Diego
2014
Abstract We present Bisque, a tool for estimating cell type proportions in bulk expression. Bisque implements regression-based approach that utilizes single-cell RNA-seq (scRNA-seq) or single-nucleus (snRNA-seq) data to generate reference expression profile and learn gene-specific transformations robustly decompose data. These significantly improve decomposition performance compared existing methods when there is significant technical variation the generation of observed Importantly,...
Embryonic heart formation requires the production of an appropriate number cardiomyocytes; likewise, cardiac regeneration following injury relies upon recovery lost cardiomyocytes. The basic helix-loop-helix (bHLH) transcription factor Hand2 has been implicated in promoting cardiomyocyte formation. It is unclear, however, whether plays instructive or permissive role during this process. Here, we find that overexpression hand2 early zebrafish embryo able to enhance production, resulting...
Single-nucleus RNA sequencing (snRNA-seq) measures gene expression in individual nuclei instead of cells, allowing for unbiased cell type characterization solid tissues. We observe that snRNA-seq is commonly subject to contamination by high amounts ambient RNA, which can lead biased downstream analyses, such as identification spurious types if overlooked. present a novel approach quantify and filter droplets experiments, called Debris Identification using Expectation Maximization (DIEM). Our...
Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options drug development. Here we perform promoter Capture Hi-C in human adipocytes investigate interactions between gene promoters distal elements as transcription-regulating mechanism contributing these phenotypes. We find promoter-interacting are enriched for...
Gene expression variance has been linked to organismal function and fitness but remains a commonly neglected aspect of molecular research. As result, we lack comprehensive understanding the patterns transcriptional across genes, how this is context-specific gene regulation function. Here, use 57 large publicly available RNA-seq data sets investigate landscape variance. These studies cover wide range tissues allowed us assess if there are consistently more or less variable genes what...
Age and obesity are dominant risk factors for several common cardiometabolic disorders, both known to impair adipose tissue function. However, the underlying cellular genetic linking aging on function have remained elusive. Adipose stem precursor cells (ASPCs) an understudied, yet crucial cell type due their deterministic adipocyte differentiation potential, which impacts capacity store fat in a metabolically healthy manner. We integrated subcutaneous (SAT) bulk (n=435) large single-nucleus...
Obesity predisposes individuals to multiple cardiometabolic disorders, including type 2 diabetes (T2D). As body mass index (BMI) cannot reliably differentiate fat from lean mass, the metabolically detrimental abdominal obesity has been estimated using waist-hip ratio (WHR). Waist-hip adjusted for (WHRadjBMI) in turn is a well-established sex-specific marker and adiposity, predictor of adverse metabolic outcomes, such as T2D. However, underlying genes regulatory mechanisms orchestrating sex...
The prevalence of non-alcoholic fatty liver disease (NAFLD), now also known as metabolic dysfunction-associated (MAFLD), is rapidly increasing worldwide due to the ongoing obesity epidemic. However, currently NALFD diagnosis requires non-readily available imaging technologies or biopsy, which has drastically limited sample sizes NAFLD studies and hampered discovery its genetic component. Here we utilized large UK Biobank (UKB) accurately estimate status in UKB based on common serum traits...
The global obesity epidemic is driving the concomitant rise in nonalcoholic fatty liver disease (NAFLD). To identify new genes involved central functions, we examined RNA-sequence data from 259 patients who underwent morbidly obese bariatric surgery. Of these patients, 84 had normal histology, 40 simple steatosis, 43 steatohepatitis, and remaining 92 varying degrees of NAFLD based on histology. We discovered oligodendrocyte maturation-associated long intergenic noncoding RNA (OLMALINC), a...
Abstract Insulin is an essential hormone that regulates glucose homeostasis and metabolism. resistance (IR) arises when tissues fail to respond insulin, it leads serious health problems including Type 2 Diabetes (T2D). Obesity a major contributor the development of IR T2D. We previously showed gene expression alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity in subcutaneous adipose tissue Mexican Americans. In current study, meta-analysis relationship between ADH1B BMI...
Abstract Obesity-induced adipose tissue dysfunction can cause low-grade inflammation and downstream obesity comorbidities. Although preadipocytes may contribute to this pro-inflammatory environment, the underlying mechanisms are unclear. We used human primary from body mass index (BMI) -discordant monozygotic (MZ) twin pairs generate epigenetic (ATAC-sequence) transcriptomic (RNA-sequence) data for testing whether increased BMI alters subnuclear compartmentalization of open chromatin in...
The Turkana people inhabit arid regions of east Africa-where temperatures are high and water is scarce-and they practice subsistence pastoralism, such that their diet primarily composed animal products. Working with communities, we sequenced 367 genomes identified 8 putatively involved in adaptation to stress pastoralism. One these includes a putative enhancer for STC1-a kidney-expressed gene the response dehydration metabolism purine-rich foods as red meat. We show STC1 induced by...
Abstract Single-nucleus RNA sequencing (snRNA-seq) measures gene expression in individual nuclei instead of cells, allowing for unbiased cell type characterization solid tissues. Contrary to single-cell seq (scRNA-seq), we observe that snRNA-seq is commonly subject contamination by high amounts extranuclear background RNA, which can lead identification spurious types downstream clustering analyses if overlooked. We present a novel approach remove debris-contaminated droplets experiments,...
Abstract Gene expression variance has been linked to organismal function and fitness but remains a commonly ne-glected aspect of molecular research. As result, we lack comprehensive understanding the patterns transcriptional across genes, how this is context-specific gene regulation function. Here, use 57 large publicly available RNA-seq data sets investigate landscape variance. These studies cover wide range tissues allowed us assess if there are consistently more or less variable genes...
Abstract Given the fast-increasing prevalence of obesity and its comorbidities, it would be critical to improve our understanding cell-type level differences between two key human adipose tissue depots, subcutaneous (SAT) visceral (VAT), in their depot-specific contributions cardiometabolic health. We integrated RNA- ATAC-seq data from SAT VAT biopsies cell-lines comprehensively elucidate transcriptomic, epigenetic, genetic fat depots. identify marker genes for specificity functional...
ABSTRACT Although recent studies provide evidence for a common genetic basis between complex traits and Mendelian disorders, thorough quantification of their overlap in phenotype-specific manner remains elusive. Here, we quantify the genes identified through large-scale genome-wide association (GWAS) 62 diseases with known to cause 20 broad categories disorders. We identify significant enrichment phenotypically-matched disorder GWAS gene sets. Further, observe elevated effect sizes near...
Obesity perturbs central functions of human adipose tissue, centred on differentiation preadipocytes to adipocytes, i.e., adipogenesis. The large environmental component obesity makes it important elucidate epigenetic regulatory factors impacting Promoter Capture Hi-C (pCHi-C) has been used identify chromosomal interactions between promoters and associated elements. However, long range (LRIs) greater than 1 Mb are often filtered out pCHi-C datasets, due technical challenges their low...