J Stamatoyannopoulos
A5006847496- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Genetic Associations and Epidemiology
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- Nuclear Physics and Applications
- Gene expression and cancer classification
- Prenatal Screening and Diagnostics
- Bioinformatics and Genomic Networks
- Biomedical Text Mining and Ontologies
- Hemoglobinopathies and Related Disorders
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
- Genomic variations and chromosomal abnormalities
- Sensor Technology and Measurement Systems
- Inorganic Fluorides and Related Compounds
- Genetic Mapping and Diversity in Plants and Animals
- Cancer Genomics and Diagnostics
- Estrogen and related hormone effects
- Advanced biosensing and bioanalysis techniques
University of Washington
2015-2024
Altius Institute for Biomedical Sciences
2016-2024
Fred Hutch Cancer Center
2023
Thermo Fisher Scientific (Sweden)
2020
Seattle University
2004-2018
Imperial College London
2012
University of Washington Medical Center
1994-2011
University of Massachusetts Chan Medical School
2010
Bar-Ilan University
2010
Brown University
2008
We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. constructed spatial proximity maps human genome Hi-C at resolution 1 megabase. These confirm presence chromosome territories and small, gene-rich chromosomes. identified an additional level organization is characterized segregation open closed chromatin to form two genome-wide compartments. At megabase scale, conformation...
The reference human genome sequence set the stage for studies of genetic variation and its association with disease, but epigenomic lack a similar reference. To address this need, NIH Roadmap Epigenomics Consortium generated largest collection so far epigenomes primary cells tissues. Here we describe integrative analysis 111 as part programme, profiled histone modification patterns, DNA accessibility, methylation RNA expression. We establish global maps regulatory elements, define modules...
Genome-wide association studies have identified many noncoding variants associated with common diseases and traits. We show that these are concentrated in regulatory DNA marked by deoxyribonuclease I (DNase I) hypersensitive sites (DHSs). Eighty-eight percent of such DHSs active during fetal development enriched gestational exposure-related phenotypes. distant gene targets for hundreds variant-containing may explain phenotype associations. Disease-associated systematically perturb...
DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery all classes cis-regulatory elements including enhancers, promoters, insulators, silencers locus control regions. Here we present first extensive map human DHSs identified through genome-wide profiling in 125 diverse cell tissue types. We identify ∼2.9 million that encompass virtually known experimentally validated sequences expose a vast trove novel elements, most with highly cell-selective...
Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding histone modifications in living cells. Despite its widespread use, there are considerable differences how these experiments conducted, results scored evaluated quality, data metadata archived public use. These practices affect quality utility any global ChIP experiment. Through our experience...
A common question within the context of de novo motif discovery is whether a newly discovered, putative resembles any previously discovered in an existing database. To answer this question, we define statistical measure motif-motif similarity, and describe algorithm, called Tomtom, for searching database motifs with given query motif. Experimental simulations demonstrate accuracy Tomtom's E values its effectiveness finding similar motifs.
The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence from the many potentially functional present in any human genome are urgently needed. Without rigorous standards we risk an acceleration false-positive reports causality, which would impede translation genomic research findings into clinical diagnostic setting hinder biological understanding disease. Here discuss key challenges assessing disease, integrating both...
Abstract Summary: The large and growing number of genome-wide datasets highlights the need for high-performance feature analysis data comparison methods, in addition to efficient storage retrieval techniques. We introduce BEDOPS, a software suite common genomic tasks which offers improved flexibility, scalability execution time characteristics over previously published packages. includes utility compress inputs into lossless format that can provide greater space savings faster extractions...
Eukaryotic chromosomes replicate in a temporal order known as the replication-timing program. In mammals, replication timing is cell-type-specific with at least half genome switching during development, primarily units of 400-800 kilobases ('replication domains'), whose positions are preserved different cell types, conserved between species, and appear to confine long-range effects chromosome rearrangements. Early late correlate, respectively, open closed three-dimensional chromatin...
Regulatory factor binding to genomic DNA protects the underlying sequence from cleavage by DNase I, leaving nucleotide-resolution footprints. Using I footprinting across 41 diverse cell and tissue types, we detected 45 million transcription occupancy events within regulatory regions, representing differential 8.4 distinct short elements. Here show that this small compartment, roughly twice size of exome, encodes an expansive repertoire conserved recognition sequences for DNA-binding proteins...
As studies of DNA methylation increase in scope, it has become evident that a complex relationship with gene expression, plays an important role defining cell types, and is disrupted many diseases. We describe large-scale single-base resolution profiling on diverse collection 82 human lines tissues using reduced representation bisulfite sequencing (RRBS). Analysis integrating RNA-seq ChIP-seq data illuminates the functional this dynamic mark. Loci are hypermethylated across cancer types...
Genome-wide association studies (GWASs) have ascertained numerous trait-associated common genetic variants, frequently localized to regulatory DNA. We found that variation at BCL11A associated with fetal hemoglobin (HbF) level lies in noncoding sequences decorated by an erythroid enhancer chromatin signature. Fine-mapping uncovers a motif-disrupting variant reduced transcription factor (TF) binding, modestly diminished expression, and elevated HbF. The surrounding function vivo as...
CTCF is a ubiquitously expressed regulator of fundamental genomic processes including transcription, intra- and interchromosomal interactions, chromatin structure. Because its critical role in genome function, binding patterns have long been assumed to be largely invariant across different cellular environments. Here we analyze genome-wide occupancy by ChIP-seq 19 diverse human cell types, normal primary cells immortal lines. We observed highly reproducible yet surprisingly plastic...
Cancer is a disease potentiated by mutations in somatic cells. are not distributed uniformly along the human genome. Instead, different genomic regions vary up to fivefold local density of cancer mutations, posing fundamental problem for statistical methods used genomics. Epigenomic organization has been proposed as major determinant mutational landscape. However, both mutagenesis and epigenomic features highly cell-type-specific. We investigated distribution multiple independent samples...
Faithful transmission of genetic material to daughter cells involves a characteristic temporal order DNA replication, which may play significant role in the inheritance epigenetic states. We developed genome-scale approach--Repli Seq--to map temporally ordered replicating using massively parallel sequencing and applied it study regional variation human replication time across multiple cell types. The method requires as few 8,000 cytometry-fractionated for single analysis, provides...