A5029206240- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- interferon and immune responses
- Influenza Virus Research Studies
- HIV Research and Treatment
- Cancer-related gene regulation
- Chromosomal and Genetic Variations
- T-cell and B-cell Immunology
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Immune responses and vaccinations
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- Children's Rights and Participation
University of Chicago
2022-2025
University of Pennsylvania
2016-2017
Gene regulation shapes the evolution of phenotypic diversity. We investigated liver promoters and enhancers in six primate species using ChIP-seq (H3K27ac H3K4me1) to profile cis-regulatory elements (CREs) RNA-seq characterize gene expression same individuals. To quantify regulatory divergence, we compared CRE activity across by testing differential read depths directly measured for orthologous sequences. show that landscape is largely conserved lineage, with 63% tested human CREs showing...
Previously, we showed that a massively parallel reporter assay, mSTARR-seq, could be used to simultaneously test for both enhancer-like activity and DNA methylation-dependent enhancer millions of loci in single experiment (Lea et al., 2018). Here, apply mSTARR-seq query nearly the entire human genome, including almost all CpG sites profiled either on commonly Illumina Infinium MethylationEPIC array or via reduced representation bisulfite sequencing. We show fragments containing these are...
Genetic variants, including mobile element insertions (MEIs), are known to impact the epigenome. We hypothesized that genome graphs, which encapsulate genetic diversity, could reveal missing epigenomic signals. To test this, we sequenced epigenome of monocyte-derived macrophages from 35 ancestrally diverse individuals before and after influenza infection, allowing us investigate role MEIs in immunity. characterized variants using linked reads built a graph. Mapping epigenetic data revealed...
Influenza A virus (IAV) infections are frequent every year and result in a range of disease severity. Here, we wanted to explore the potential contribution transposable elements (TEs) variable human immune response. Transcriptome profiling monocyte-derived macrophages from 39 individuals following IAV infection revealed significant inter-individual variation viral load post-infection. Using transposase-accessible chromatin using sequencing (ATAC-seq), identified set TE families with either...
Previously, we showed that a massively parallel reporter assay, mSTARR-seq, could be used to simultaneously test for both enhancer-like activity and DNA methylation-dependent enhancer millions of loci in single experiment (Lea et al., 2018). Here, apply mSTARR-seq query nearly the entire human genome, including almost all CpG sites profiled either on commonly Illumina Infinium MethylationEPIC array or via reduced representation bisulfite sequencing. We show fragments containing these are...
SUMMARY Influenza A virus (IAV) infections are frequent every year and result in a range of disease severity. Given that transposable elements (TEs) contribute to the activation innate immunity, we wanted explore their potential role this variability. Transcriptome profiling monocyte-derived macrophages from 39 individuals following IAV infection revealed significant inter-individual variation viral load post-infection. Using ATAC-seq identified set TE families with either enhanced or...
Summary Humans display remarkable inter-individual variation in immune response when exposed to identical challenges. Yet, our understanding of the genetic and epigenetic factors contributing such remains limited. Here we carried out in-depth genetic, epigenetic, transcriptional profiling on primary macrophages derived from a panel European African-ancestry individuals before after infection with influenza A virus (IAV). We show that baseline profiles are strongly predictive IAV across...
Abstract Gene regulation plays a critical role in the evolution of phenotypic diversity. We investigated liver promoters and enhancers six primate species. performed ChlP-seq for two histone modifications RNA-seq to profile cis-regulatory element (CRE) activity gene expression. The regulatory landscape is largely conserved across lineage. Conserved CRE function associated with sequence conservation, proximity coding genes, cell type specificity function, transcription factor binding. Newly...
Previously we showed that a massively parallel reporter assay, mSTARR-seq, could be used to simultaneously test for both enhancer-like activity and DNA methylation-dependent enhancer millions of loci in single experiment (Lea et al., 2018). Here apply mSTARR-seq query nearly the entire human genome, including almost all CpG sites profiled either on commonly Illumina Infinium MethylationEPIC array or via reduced representation bisulfite sequencing. We show fragments containing these are...
Previously we showed that a massively parallel reporter assay, mSTARR-seq, could be used to simultaneously test for both enhancer-like activity and DNA methylation-dependent enhancer millions of loci in single experiment (Lea et al ., 2018). Here apply mSTARR-seq query nearly the entire human genome, including almost all CpG sites profiled either on commonly Illumina Infinium MethylationEPIC array or via reduced representation bisulfite sequencing. We show fragments containing these are...
Human epigenomic data has been generated by large consortia for thousands of cell types to be used as a reference map normal and disease chromatin states. Since epigenetic contains potentially identifiable information, similarly genetic data, most raw files these are stored in controlled-access databases. It is important protect but this should not hinder secure sharing valuable datasets.
Abstract Genetic variants, including mobile element insertions (MEIs), are known to impact the epigenome. We hypothesized that use of a genome graph, which encapsulates genetic diversity, could reveal missing epigenomic signal. Given contributions elements evolution primate innate immunity, we tested this in monocyte-derived macrophages obtained from 35 individuals before and after Influenza virus infection. After characterizing variants cohort using linked-reads, 5140 Alu, 316 L1, 94 SVAs...
Abstract Previously we showed that a massively parallel reporter assay, mSTARR-seq, could be used to simultaneously test for both enhancer-like activity and DNA methylation-dependent enhancer millions of loci in single experiment (Lea et al., 2018). Here apply mSTARR-seq query nearly the entire human genome, including almost all CpG sites profiled either on commonly Illumina Infinium MethylationEPIC array or via reduced representation bisulfite sequencing. We show fragments containing these...
Human epigenomic data has been generated by large consortia for thousands of cell types to be used as a reference map normal and disease chromatin states. Since epigenetic contains potentially identifiable information, similarly genetic data, most raw files these are stored in controlled-access databases. It is important protect but this should not hinder secure sharing valuable datasets.