A5001206200- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- Genetic Mapping and Diversity in Plants and Animals
- Music and Audio Processing
- Pleistocene-Era Hominins and Archaeology
- RNA modifications and cancer
- Genetic Associations and Epidemiology
- Forensic Anthropology and Bioarchaeology Studies
- Neuroscience and Music Perception
- Autism Spectrum Disorder Research
- Forensic and Genetic Research
- Epigenetics and DNA Methylation
- Obsessive-Compulsive Spectrum Disorders
- Diverse Music Education Insights
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Global Maternal and Child Health
- Genetic Neurodegenerative Diseases
- Evolution and Genetic Dynamics
- Genomics and Phylogenetic Studies
- Archaeology and ancient environmental studies
- Genetics, Aging, and Longevity in Model Organisms
- Chemical Reaction Mechanisms
- Protein Degradation and Inhibitors
University of Washington
2023-2025
University of California, San Francisco
2022-2025
Vanderbilt University Medical Center
2019-2024
Vanderbilt University
2017-2024
University of North Carolina at Chapel Hill
2013-2015
SIT Graduate Institute
2015
Moving in synchrony to the beat is a fundamental component of musicality. Here we conducted genome-wide association study identify common genetic variants associated with synchronization 606,825 individuals. Beat exhibited highly polygenic architecture, 69 loci reaching significance (P < 5 × 10
Eurasians have ~2% Neanderthal ancestry, but we lack a comprehensive understanding of the genome-wide influence introgression on modern human diseases and traits. Here, quantify contribution introgressed alleles to heritability more than 400 diverse We show that genomic regions in which detectable ancestry remains are depleted for all traits considered, except those related skin hair. Introgressed variants themselves also contributions most However, shared across multiple populations...
Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on genetic etiology underlying biological mechanisms disorder. We conducted GWAS meta-analysis combining 53,660 OCD cases 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent significant SNPs SNP-based heritability 6.7%. Separate for clinical, biobank, comorbid, self-report...
Abstract Changes in gene regulation were a major driver of the divergence archaic hominins (AHs)—Neanderthals and Denisovans—and modern humans (MHs). The three-dimensional (3D) folding genome is critical for regulating expression; however, its role recent human evolution has not been explored because degradation ancient samples does permit experimental determination AH 3D folding. To fill this gap, we apply novel deep learning methods inferring organization from DNA sequence to Neanderthal,...
Comparing chromatin contact maps is an essential step in quantifying how three-dimensional (3D) genome organization shapes development, evolution, and disease. However, no gold standard exists for comparing maps, even simple methods often disagree. In this study, we propose novel comparison evaluate them alongside existing approaches using genome-wide Hi-C data 22,500
Obsessive-compulsive disorder (OCD) is a heritable disorder, but no definitive, replicated OCD susceptibility loci have yet been identified by any genome-wide association study (GWAS). Here, we report results from GWAS in the largest case-control sample (N = 14,140 cases and N 562,117 controls) to date. We explored genetic architecture of OCD, including its relationships other psychiatric non-psychiatric phenotypes. In analysis, one SNP associated with at significant level. Subsequent...
Abstract Comparing chromatin contact maps is an essential step in quantifying how three-dimensional (3D) genome organization shapes development, evolution, and disease. However, methods often disagree, no gold standard exists for comparing pairs of maps. Here, we evaluate 25 ways to compare using Micro-C Hi-C data from two cell types silico-generated We identify similarities differences between the quantify their robustness common sources biological technical variation, including losses...
Enabling discovery across the spectrum of rare and common diseases requires integration biological knowledge with clinical data; however, differences in terminologies present a major barrier. For example, Human Phenotype Ontology (HPO) is primary vocabulary for describing features diseases, while most encounters use International Classification Diseases (ICD) billing codes. ICD codes are further organized into clinically meaningful phenotypes via phecodes. Despite their prevalence, no robust...
Genome-wide association studies aim to correlate genotype with phenotype. Many common diseases including Type II diabetes, Alzheimer's, Parkinson's and Chronic Obstructive Pulmonary Disease (COPD) are complex genetic traits hundreds of different loci that associated varied disease risk. Identifying features in the genes each remains a challenge. Furthermore, role post-transcriptional regulation, particular alternative splicing, is still poorly understood most multigenic diseases. We...
The impact of inherited and somatic mutations on messenger RNA (mRNA) structure remains poorly understood. Recent technological advances that leverage next-generation sequencing to obtain experimental data, such as SHAPE-MaP, can reveal structural effects mutations, especially when these data are incorporated into modeling. Here, we analyze the ability SHAPE-MaP detect relatively subtle changes caused by single-nucleotide mutations. We find allele-specific sorting greatly improved our...
In India, only one woman is diagnosed with tuberculosis (TB) for every 2.4 men. Previous studies have indicated gender disparities in care-seeking behavior and TB diagnosis; however, little known about the specific barriers women face.This study aimed to characterize socio-cultural knowledge-based that affected diagnosis Bhopal, India.In-depth interviews were conducted 13 6 health-care workers. The Bhopal Diagnostic Microscopy Laboratory Register (n = 121) district report 261) examined...
Abstract The 3D structure of the genome is an important mediator gene expression. As phenotypic divergence largely driven by regulatory variation, comparing contacts across species can further understanding molecular basis differences. However, while experimental data on in humans are increasingly abundant, only a handful contact maps exist for other species. Here, we demonstrate that human be used to close this gap. We apply machine learning model predicts from DNA sequence genomes 56...
Abstract Understanding variation in chromatin contact patterns across diverse humans is critical for interpreting noncoding variants and their effects on gene expression phenotypes. However, experimental determination of large samples prohibitively expensive. To overcome this challenge, we develop validate a machine learning method to quantify the 3D contacts at 2 kilobase resolution from genome sequence alone. We apply approach thousands human genomes 1000 Genomes Project inferred hominin...
Abstract When the ancestors of modern Eurasians migrated out Africa and interbred with Eurasian archaic hominins, namely, Neanderthals Denisovans, DNA ancestry integrated into genomes anatomically humans. This process potentially accelerated adaptation to environmental factors, including reduced ultraviolet radiation increased variation in seasonal dynamics. However, whether these groups differed substantially circadian biology introgression adaptively contributed human chronotypes remain...
Abstract Moving in synchrony to the beat is a fundamental component of musicality. Here, we conducted genome-wide association study (GWAS) identify common genetic variants associated with synchronization 606,825 individuals. Beat exhibited highly polygenic architecture, sixty-nine loci reaching significance (p<5×10 −8 ) and SNP-based heritability (on liability scale) 13%-16%. Heritability was enriched for genes expressed brain tissues, fetal adult brain-specific gene regulatory elements,...
Establishment of DNA methylation (DNAme) patterns is essential for balanced multi-lineage cellular differentiation, but exactly how these drive phenotypes unclear. While > 80% CpG sites are stably methylated, tens thousands discrete loci form hypomethylated regions (HMRs). Because they lack DNAme, HMRs considered transcriptionally permissive, not all actively regulate genes. Unlike promoter HMRs, a subset non-coding cell type-specific and enriched tissue-specific gene regulatory functions....
Abstract In this paper, we present results of a laboratory study in which participants completed an asynchronous collaborative search task while thinking aloud. Based on analysis the think‐aloud data and screen recordings, set actions rationales that our employed. For each, describe purpose motivations, give illustrative examples. We also three high‐level strategies (independent, parallel, divergent) emerged from participants' verbalizations discuss how used these as part their overall...
ABSTRACT Neanderthal ancestry remains across modern Eurasian genomes, and introgressed sequences influence diverse phenotypes, including immune, skin, neuropsychiatric diseases. Interpretation of has focused on alleles derived in the lineage. Here, we demonstrate that introgression also reintroduced thousands ancestral hominin lost out Africa bottleneck. Combining evolutionary simulations, expression quantitative trait loci (eQTL), massively parallel reporter assay (MPRA) data, vitro...
ABSTRACT Topologically associating domains (TADs) are fundamental units of three-dimensional (3D) nuclear organization. The regions bordering TADs—TAD boundaries—contribute to the regulation gene expression by restricting interactions cis-regulatory sequences their target genes. TAD and boundary disruption have been implicated in rare disease pathogenesis; however, we a limited framework for integrating TADs variation across cell types into interpretation common trait-associated variants....
Comparing chromatin contact maps is an essential step in quantifying how three-dimensional (3D) genome organization shapes development, evolution, and disease. However, no gold standard exists for comparing maps, even simple methods often disagree. In this study, we propose novel comparison evaluate them alongside existing approaches using genome-wide Hi-C data 22,500 silico predicted maps. We also quantify the robustness of to common sources biological technical variation, such as boundary...