A5007861233- Pancreatic function and diabetes
- Diabetes and associated disorders
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- Coastal wetland ecosystem dynamics
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Diabetes Management and Research
- Genetic diversity and population structure
- Marine and coastal plant biology
- Genomics and Chromatin Dynamics
- Chromatin Remodeling and Cancer
- Genetic Mapping and Diversity in Plants and Animals
- Constructed Wetlands for Wastewater Treatment
- Genetic Associations and Epidemiology
- Immune Cell Function and Interaction
- State Capitalism and Financial Governance
- Cannabis and Cannabinoid Research
- GABA and Rice Research
- Glycosylation and Glycoproteins Research
- Genetics and Neurodevelopmental Disorders
- Diet, Metabolism, and Disease
- Plant responses to water stress
- Global Financial Regulation and Crises
- T-cell and B-cell Immunology
Salk Institute for Biological Studies
2022-2025
University of California, San Diego
2015-2024
UC San Diego Health System
2022
We present BUSTED, a new approach to identifying gene-wide evidence of episodic positive selection, where the non-synonymous substitution rate is transiently greater than synonymous rate. BUSTED can be used either on an entire phylogeny (without requiring priori hypothesis regarding which branches are under selection) or pre-specified subset foreground lineages (if suitable available). Selection modeled as varying stochastically over and sites, we propose computationally inexpensive metric...
Abstract Genetic variants affecting pancreatic islet enhancers are central to T2D risk, but the gene targets of enhancer activity largely unknown. We generate a high-resolution map chromatin loops using Hi-C assays in three samples and use annotate target genes defined ATAC-seq published ChIP-seq data. identify candidate for thousands enhancers, find that looping is correlated with islet-specific expression. fine-map risk these eQTL mapping enriched protein transport secretion pathways. At...
Gene regulation is highly cell type-specific and understanding the function of non-coding genetic variants associated with complex traits requires molecular phenotyping at type resolution. In this study we performed single nucleus ATAC-seq (snATAC-seq) genotyping in peripheral blood mononuclear cells from 13 individuals. Clustering chromatin accessibility profiles 96,002 total nuclei identified 17 immune types sub-types. We mapped QTLs (caQTLs) each sub-type using individuals European...
Cannabis sativa is a globally significant seed-oil, fiber, and drug-producing plant species. However, century of prohibition has severely restricted legal breeding germplasm resource development, leaving potential hemp-based nutritional fiber applications unrealized. Existing cultivars are highly heterozygous lack competitiveness in the overall grain markets, relegating hemp to less than 200,000 hectares globally1. The relaxation drug laws recent decades generated widespread interest...
Summary The Lemnaceae (duckweeds) are the world’s smallest but fastest growing flowering plants. Prolific clonal propagation facilitates continuous micro-cropping for plant-based protein and starch production, holds tremendous promise sequestration of atmospheric CO 2 . Here, we present chromosomal assemblies, annotations, phylogenomic analysis Lemna genomes that uncover candidate genes responsible metabolic developmental traits family, such as anatomical reduction, adaxial stomata, lack...
Summary Over 15 families of aquatic plants are known to use a strategy developmental switching upon environmental stress produce dormant propagules called turions. However, few molecular details for turion biology have been elucidated due the difficulties in isolating high‐quality nucleic acids from this tissue. We successfully developed new protocol isolate transcripts and carried out RNA‐seq analysis mature turions Greater Duckweed Spirodela polyrhiza . Comparison transcriptomes that...
The extent to which shared genetic risk contributes T1D and T2D etiology is unknown. In this study, we generated association data of 15k samples imputed into the HRC panel compared published 1000 Genomes. effects variants on at known loci genome-wide were positively correlated. Increased was correlated with higher fasting insulin glucose level decreased birth weight, among other correlations. Variants further enriched in pancreatic, adipose, B cell, endoderm regulatory elements. We...
Abstract Summary Pangenomes are replacing single reference genomes as the definitive representation of DNA sequence within a species or clade. Pangenome analysis predominantly leverages graph-based methods that require computationally intensive multiple genome alignments, do not scale to highly complex eukaryotic genomes, limit their scope identifying structural variants (SVs), incur bias by relying on genome. Here, we present PanKmer, toolkit designed for reference-free pangenome datasets...
The Lemnaceae (duckweeds) are the world's smallest but fastest-growing flowering plants. Prolific clonal propagation facilitates continuous micro-cropping for plant-based protein and starch production holds tremendous promise sequestration of atmospheric CO2. Here, we present chromosomal assemblies, annotations, phylogenomic analysis Lemna genomes that uncover candidate genes responsible unique metabolic developmental traits family, such as anatomical reduction, adaxial stomata, lack...
Abstract Most asset pricing theories suggest that prices are forward looking and reflect market expectations of future earnings. By aggregating across companies, aggregate may then be used as leading indicators growth in income, well its constituent components. Data compiled from 23 countries, including 15 developing order to examine the ability stock predict economic consumption investment. It is found generally have predictive ability, but with substantial variation countries. Moreover,...
We combined functional genomics and human genetics to investigate processes that affect type 1 diabetes (T1D) risk by mediating beta cell survival in response proinflammatory cytokines. mapped 38,931 cytokine-responsive candidate cis-regulatory elements (cCREs) cells using ATAC-seq snATAC-seq linked them target genes co-accessibility HiChIP. Using a genome-wide CRISPR screen EndoC-βH1 cells, we identified 867 affecting cytokine-induced survival, promoting up-regulated cytokines were enriched...
Genetic variants associated with type 2 diabetes (T2D) risk affect gene regulation in metabolically relevant tissues, such as pancreatic islets. Here, we investigated contributions of regulatory programs active during development to T2D risk. Generation chromatin maps from developmental precursors throughout differentiation human embryonic stem cells (hESCs) identifies enrichment progenitor-specific stretch enhancers that are not Genes predicted regulate processes, most notably tissue...
Glucocorticoids are key regulators of glucose homeostasis and pancreatic islet function, but the gene regulatory programs driving responses to glucocorticoid signaling in islets contribution these diabetes risk unknown. In this study we used ATAC-seq RNA-seq map chromatin accessibility expression from eleven primary human samples cultured vitro with dexamethasone at multiple doses durations. We identified thousands accessible sites genes significant changes activity response glucocorticoids....
Abstract DNA, RNA, and proteins are synthesized using template molecules, but glycosylation is not believed to be constrained by a template. However, if cellular environment the only determinant of glycosylation, all sites should receive same glycans on average. This template-free assertion inconsistent with observations microheterogeneity—wherein each site receives distinct reproducible glycan structures. Here, we test assumption biosynthesis. Through structural analysis site-specific data,...
Abstract Gene regulation is highly cell type-specific and understanding the function of non-coding genetic variants associated with complex traits requires molecular phenotyping at type resolution. In this study we performed single nucleus ATAC-seq (snATAC-seq) genotyping in peripheral blood mononuclear cells from 10 individuals. Clustering chromatin accessibility profiles 66,843 total nuclei identified 14 immune types sub-types. We mapped QTLs (caQTLs) each sub-type which 6,248 caQTLs,...
ABSTRACT Genetic variants associated with type 2 diabetes (T2D) risk affect gene regulation in metabolically relevant tissues, such as pancreatic islets. Here, we investigated contributions of regulatory programs active during development to T2D risk. Generation chromatin maps from developmental precursors throughout differentiation human embryonic stem cells (hESCs) identifies enrichment progenitor-specific stretch enhancers that are not Genes predicted regulate processes, most notably...
Abstract The gene targets of enhancer activity in pancreatic islets are largely unknown, impeding discovery islet regulatory networks involved type 2 diabetes (T2D) risk. We mapped chromatin state, accessibility and conformation using ChIP-seq, ATAC-seq Hi-C human islets, which we integrated with T2D genetic fine-mapping expression QTL data. Active elements preferentially interacted other active elements, often at distances over 1MB, identified target genes for thousands distal enhancers. A...
Abstract Glucocorticoids are key regulators of glucose homeostasis and pancreatic islet function, but the gene regulatory programs driving responses to glucocorticoid signaling in islets contribution these diabetes risk unknown. In this study we used ATAC-seq RNA-seq map chromatin accessibility expression from eight primary human samples cultured vitro with dexamethasone. We identified 2,838 accessible sites 1,114 genes significant changes activity response glucocorticoids. Chromatin...
ABSTRACT Beta cells intrinsically contribute to the pathogenesis of type 1 diabetes (T1D), but genes and molecular processes that mediate beta cell survival in T1D remain largely unknown. We combined high throughput functional genomics human genetics identify risk loci regulating affecting response proinflammatory cytokines IL-1β, IFNγ, TNFα. mapped 38,931 cytokine-responsive candidate cis -regulatory elements (cCREs) active using ATAC-seq single nuclear (snATAC-seq), linked cCREs putative...
Abstract The role of shared genetic risk in the etiology type 1 diabetes (T1D) and 2 (T2D) mechanisms these effects is unknown. In this study, we generated T1D association data 15k samples imputed into HRC reference panel which compared to T2D 159k 1000 Genomes. variants on at known loci genome-wide were positively correlated, replicated using from UK Biobank clinically-defined WTCCC. Increased was correlated with higher fasting insulin glucose level decreased birth weight, among T1D-...
Abstract Summary Pangenomes are replacing single reference genomes as the definitive representation of DNA sequence within a species or clade. Pangenome analysis predominantly leverages graph-based methods that require computationally intensive multiple genome alignments, do not scale to highly complex eukaryotic genomes, limit their scope identifying structural variants (SVs), incur bias by relying on genome. Here, we present PanKmer, toolkit designed for reference-free pangenome datasets...
Abstract Sample preservation often impedes efforts to generate high-quality reference genomes or pangenomes for Earth’s more than 2 million plant and animal species due nucleotide degradation. Here we compare the impacts of storage methods including solution type, temperature, time on DNA quality Oxford Nanopore long-read sequencing in 9 fish 4 species. We show 95% ethanol largely protects against degradation blood (22 °C, ≤6 weeks) tissue (4 ≤3 weeks). From this furthest timepoint, assemble...
Summary Over 15 families of aquatic plants are known to use a strategy developmental switching upon environmental stress produce dormant propagules called turions. However, few molecular details for turion biology have been elucidated due the difficulties in isolating high-quality nucleic acids from this tissue. We successfully developed new protocol isolate transcripts and carried out RNA-seq analysis mature turions Greater Duckweed Spirodela polyrhiza . Comparison transcriptome that...