A5022780099- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Pancreatic function and diabetes
- Single-cell and spatial transcriptomics
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Diabetes and associated disorders
- Immune cells in cancer
- Immune responses and vaccinations
- Endoplasmic Reticulum Stress and Disease
- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Gene Regulatory Network Analysis
- Genetic Syndromes and Imprinting
- RNA Research and Splicing
- Telomeres, Telomerase, and Senescence
- Genomics and Phylogenetic Studies
- Error Correcting Code Techniques
- COVID-19 Clinical Research Studies
- Genetics, Aging, and Longevity in Model Organisms
- Genomic variations and chromosomal abnormalities
- Chemokine receptors and signaling
- Cancer Genomics and Diagnostics
- Machine Learning in Bioinformatics
- COVID-19 Impact on Reproduction
Jackson Laboratory
2018-2025
UConn Health
2022
University of Connecticut
2016-2018
EndoC-βH1 is emerging as a critical human β cell model to study the genetic and environmental etiologies of (dys)function diabetes. Comprehensive knowledge its molecular landscape lacking, yet required, for effective use this model. Here, we report chromosomal (spectral karyotyping), (genotyping), epigenomic (ChIP-seq ATAC-seq), chromatin interaction (Hi-C Pol2 ChIA-PET), transcriptomic (RNA-seq miRNA-seq) maps EndoC-βH1. Analyses these define known (e.g., PDX1 ISL1) putative PCSK1 mir-375)...
Abstract Detecting multiplets in single nucleus (sn)ATAC-seq data is challenging due to sparsity and limited dynamic range. AMULET (ATAC-seq MULtiplet Estimation Tool) enumerates regions with greater than two uniquely aligned reads across the genome effectively detect multiplets. We evaluate method by generating snATAC-seq human blood pancreatic islet samples. has high precision, estimated via donor-based multiplexing, recall, simulated multiplets, compared alternatives identifies most when...
Broad domain promoters and super enhancers are regulatory elements that govern cell-specific functions harbor disease-associated sequence variants. These characterized by distinct epigenomic profiles, such as expanded deposition of histone marks H3K27ac for H3K4me3 broad domains, however little is known about how they interact with each other the rest genome in three-dimensional chromatin space. Using network theory methods, we studied interactions between domains three ENCODE cell lines...
<title>Abstract</title> Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection hospitalizations in infants and poses a significantly higher risk failure than SARS-CoV-2. The mechanisms underlying these differences remain unclear. We analyzed blood samples from (median age 2.3 months) with SARS-CoV-2 (n = 30), RSV 19), healthy controls 17) using single-cell transcriptomics epigenomics, cytokine profiling. Both viruses triggered comparable interferon...
Enhancers are cis-acting sequences that regulate transcription rates of their target genes in a cell-specific manner and harbor disease-associated sequence variants cognate cell types. Many complex diseases associated with enhancer malfunction, necessitating the discovery study enhancers from clinical samples. Assay for Transposase Accessible Chromatin (ATAC-seq) technology can interrogate chromatin accessibility small numbers facilitate studying pathologies. However, on average, ~35% open...
Abstract Severe coronavirus disease 2019 (COVID-19) is characterized by systemic inflammation and can result in protracted symptoms. Robust may trigger persistent changes hematopoietic cells innate immune memory through epigenetic mechanisms. We reveal that rare circulating stem progenitor (HSPC), enriched from human blood, match the diversity of HSPC bone marrow, enabling investigation hematopoiesis epigenomics. Following COVID-19, retain epigenomic alterations are conveyed,...
Monocytes can differentiate into macrophages (Mo-Macs) or dendritic cells (Mo-DCs). The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the differentiation of monocytes Mo-Macs, while combination GM-CSF/interleukin (IL)-4 is widely used to generate Mo-DCs for clinical applications and study human DC biology. Here, we report that pharmacological inhibition nuclear receptor peroxisome proliferator-activated gamma (PPARγ) in presence GM-CSF absence IL-4 monocyte...
Recent studies of the human genome have indicated that regulatory elements (e.g. promoters and enhancers) at distal genomic locations can interact with each other via chromatin folding affect gene expression levels. Genomic technologies for mapping interactions between DNA regions, e.g., ChIA-PET HiC, generate genome-wide maps elements. These interaction datasets are important resources to infer targets non-coding facilitate prioritization critical loci cellular functions. With increasing...
Endoplasmic reticulum (ER) and inflammatory stress responses contribute to islet dysfunction in type 2 diabetes (T2D). Comprehensive genomic understanding of these human whether T2D-associated genetic variants modulate them is lacking. Here, comparative transcriptome epigenome analyses islets exposed ex vivo stressors revealed 30% expressed genes 14% cis-regulatory elements (CREs) as responsive, modulated largely an ER- or cytokine-specific fashion. T2D overlapped 86 stress-responsive CREs,...
Cis -Regulatory elements ( cis -REs) include promoters, enhancers, and insulators that regulate gene expression programs via binding of transcription factors. ATAC-seq technology effectively identifies active -REs in a given cell type (including from single cells) by mapping accessible chromatin at base-pair resolution. However, these maps are not immediately useful for inferring specific functions -REs. For this purpose, we developed deep learning framework (CoRE-ATAC) with novel data...
ABSTRACT Endoplasmic reticulum (ER) and inflammatory stress responses are two pathophysiologic factors contributing to islet dysfunction failure in Type 2 Diabetes (T2D). However, how human cells respond these stressors whether T2D-associated genetic variants modulate is unknown. To fill this knowledge gap, we profiled transcriptional (RNA-seq) epigenetic (ATAC-seq) remodeling islets exposed ex vivo ER (thapsigargin) or (IL-1β+IFN-γ) stress. 5,427 genes (∼32%) were associated with responses;...
Abstract Cis -Regulatory elements (cis-REs) include promoters, enhancers, and insulators that regulate gene expression programs via binding of transcription factors. ATAC-seq technology effectively identifies active cis -REs in a given cell type (including from single cells) by mapping accessible chromatin at base-pair resolution. However, these maps are not immediately useful for inferring specific functions -REs. For this purpose, we developed deep learning framework (CoRE-ATAC) with novel...
SUMMARY EndoC-βH1 is emerging as a critical human beta cell model to study the genetic and environmental etiologies of function, especially in context diabetes. Comprehensive knowledge its molecular landscape lacking yet required fully take advantage this model. Here, we report extensive chromosomal (spectral karyotyping), (genotyping), epigenetic (ChIP-seq, ATAC-seq), chromatin interaction (Hi-C, Pol2 ChIA-PET), transcriptomic (RNA-seq, miRNA-seq) maps Integrated analyses these define known...
ABSTRACT Similar to other droplet-based single cell assays, nucleus ATAC-seq (snATAC-seq) data harbor multiplets that confound downstream analyses. Detecting in snATAC-seq is particularly challenging due its sparsity and trinary nature (0 reads: closed chromatin, 1: open one allele, 2: both alleles), yet offers a unique opportunity infer when >2 uniquely aligned reads are observed at multiple loci. Here, we implemented the first read count-based multiplet detection method,...
Current approaches for pathway analyses focus on representing gene expression levels graph representations of pathways and conducting enrichment among differentially expressed genes. However, by themselves do not reflect the overall picture as non-coding factors play an important role to regulate expression. To incorporate these into systematically prioritize genes in a we introduce new software: Triangulation Perturbation Origins Identification Non-Coding Targets. Targets is analysis tool,...