Steven K. Reilly
A5069908459- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Cardiac, Anesthesia and Surgical Outcomes
- SARS-CoV-2 and COVID-19 Research
- Genetic Associations and Epidemiology
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Developmental Biology and Gene Regulation
- Genetic diversity and population structure
- SARS-CoV-2 detection and testing
- Single-cell and spatial transcriptomics
- COVID-19 epidemiological studies
- Enhanced Recovery After Surgery
- Genomics and Rare Diseases
- Bioinformatics and Genomic Networks
- COVID-19 and healthcare impacts
- RNA modifications and cancer
- Bat Biology and Ecology Studies
- interferon and immune responses
- Marine animal studies overview
- Respiratory Support and Mechanisms
Yale University
2010-2024
North Middlesex Hospital
2024
Middlesex University
2024
Broad Institute
2016-2023
Howard Hughes Medical Institute
2023
University of California, Santa Cruz
2023
University of California, Riverside
2023
Morningside College
2023
University of Massachusetts Chan Medical School
2023
Science for Life Laboratory
2023
Is there a global consensus on the management of endometriosis that considers views women with endometriosis?It was possible to produce an international statement current through engagement representatives national and international, medical non-medical societies interest in endometriosis.Management anywhere world has been based partially evidence-based practices unsubstantiated therapies approaches. Several guidelines have developed by number bodies, yet areas controversy uncertainty...
Abstract Recent studies implicate chromatin modifiers in autism spectrum disorder (ASD) through the identification of recurrent de novo loss function mutations affected individuals. ASD risk genes are co-expressed human midfetal cortex, suggesting that converge specific regulatory networks during neurodevelopment. To elucidate such networks, we identify targeted by CHD8, a chromodomain helicase strongly associated with ASD, brain, neural stem cells (hNSCs) and embryonic mouse cortex. CHD8...
Human higher cognition is attributed to the evolutionary expansion and elaboration of human cerebral cortex. However, genetic mechanisms contributing these developmental changes are poorly understood. We used comparative epigenetic profiling human, rhesus macaque, mouse corticogenesis identify promoters enhancers that have gained activity in humans. These gains significantly enriched modules coexpressed genes cortex function neuronal proliferation, migration, cortical-map organization....
Phylogenetics of superspreading One important characteristic coronavirus epidemiology is the occurrence events. These are marked by a disproportionate number cases originating from often-times asymptomatic individuals. Using rich sequence dataset early stages Boston outbreak, Lemieux et al. identified events in specific settings and analyzed them phylogenetically (see Perspective Alizon). ancestral trait inference, authors several importation events, further investigated context contribution...
Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes 240 species, we identify bases that, when mutated, are likely affect fitness and alter disease risk. At least 332 million (~10.7%) in human genome unusually conserved across species (evolutionarily constrained) relative neutrally evolving repeats, 4552 ultraconserved elements nearly perfectly conserved. Of 101 significantly constrained single bases, 80% outside protein-coding exons half...
Annotating coding genes and inferring orthologs are two classical challenges in genomics evolutionary biology that have traditionally been approached separately, limiting scalability. We present TOGA (Tool to infer Orthologs from Genome Alignments), a method integrates structural gene annotation orthology inference. implements different paradigm orthologous loci, improves ortholog detection of conserved compared with state-of-the-art methods, handles even highly fragmented assemblies. scales...
The precise pattern and timing of speciation events that gave rise to all living placental mammals remain controversial. We provide a comprehensive phylogenetic analysis genetic variation across an alignment 241 mammal genome assemblies, addressing prior concerns regarding limited genomic sampling species. compared neutral genome-wide phylogenomic signals using concatenation coalescent-based approaches, interrogated chromosomes, analyzed extensive catalogs structural variants. Interordinal...
Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability discern which positions functionally important. Evolutionary constraint is a powerful predictor function, agnostic cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% the genome as significantly constrained and likely functional. We compared annotation, association studies, copy-number variation,...
We examined transposable element (TE) content of 248 placental mammal genome assemblies, the largest de novo TE curation effort in eukaryotes to date. found that although mammals resemble one another total and diversity, they show substantial differences with regard recent accumulation. This includes multiple expansion quiescence events across mammalian tree. Young TEs, particularly long interspersed elements, drive increases size, whereas DNA transposons are associated smaller genomes....
Human accelerated regions (HARs) are conserved genomic loci that evolved at an rate in the human lineage and may underlie human-specific traits. We generated HARs chimpanzee with automated pipeline alignment of 241 mammalian genomes. Combining deep learning chromatin capture experiments neural progenitor cells, we discovered a significant enrichment topologically associating domains containing variants change three-dimensional (3D) genome organization. Differential gene expression between...
Understanding the regulatory landscape of human genome is a long-standing objective modern biology. Using reference-free alignment across 241 mammalian genomes produced by Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million candidate cis-regulatory elements (cCREs) and 15.6 transcription factor binding sites (TFBSs). We identified 439,461 cCREs 2,024,062 TFBSs under constraint. Genes near constrained perform fundamental cellular processes, whereas genes...
Species persistence can be influenced by the amount, type, and distribution of diversity across genome, suggesting a potential relationship between historical demography resilience. In this study, we surveyed genetic variation single genomes 240 mammals that compose Zoonomia alignment to evaluate how effective population size (
Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent functionally conserved despite low sequence conservation. We developed Tissue-Aware Conservation Inference Toolkit (TACIT) associate candidate with species' using predictions from machine learning...
Cis-regulatory elements (CREs) control gene expression, orchestrating tissue identity, developmental timing and stimulus responses, which collectively define the thousands of unique cell types in body
Abstract The ENCODE Consortium’s efforts to annotate noncoding cis -regulatory elements (CREs) have advanced our understanding of gene regulatory landscapes. Pooled, CRISPR screens offer a systematic approach investigate mechanisms. ENCODE4 Functional Characterization Centers conducted 108 in human cell lines, comprising >540,000 perturbations across 24.85 megabases the genome. Using 332 functionally confirmed CRE–gene links K562 cells, we established guidelines for screening endogenous...
The regulatory elements that direct tissue-specific gene expression in the developing mammalian embryo remain largely unknown. Although chromatin profiling has proven to be a powerful method for mapping sequences cultured cells, states characteristic of active developmental enhancers have not been directly identified embryonic tissues. Here we use whole-transcriptome analysis coupled with genome-wide H3K27ac and H3K27me3 map mouse forelimb hindlimb. We show gene-expression differences...
Cohesin is implicated in establishing tissue-specific DNA loops that target enhancers to promoters, and also localizes sites bound by the insulator protein CTCF, which blocks enhancer-promoter communication. However, cohesin-associated interactions have not been characterized on a genome-wide scale. Here we performed chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) of cohesin subunit SMC1A developing mouse limb. We identified 2264 interactions, 1491 (65%) involved...
Morphological innovations such as the mammalian neocortex may involve evolution of novel regulatory sequences. However, de novo birth elements active during morphogenesis has not been extensively studied in mammals. Here, we use H3K27ac-defined human and mouse corticogenesis to identify enhancers that were likely ancient forebrain. We infer phylogenetic origins these find ∼20% arose stem lineage, coincident with emergence neocortex. Implementing a permutation strategy controls for nonrandom...
Significance Uniquely human biology is the result of genetic differences between humans and other primates, but identifying critical changes still poses a major challenge. We screened >32,000 human-specific substitutions in two classes putative transcriptional enhancers implicated evolution for their effects on enhancer activity neural stem cells, cell type fundamental cortical development expansion. identify hundreds that modify either alone or combination with variants. find different...
Abstract Despite the great success of genome-wide association studies (GWAS) in identifying genetic loci significantly associated with diseases, vast majority causal variants underlying disease-associated have not been identified 1–3 . To create an atlas variants, we performed and integrated fine-mapping across 148 complex traits three large-scale biobanks (BioBank Japan 4,5 , FinnGen 6 UK Biobank 7,8 ; total n = 811,261), resulting 4,518 variant-trait pairs high posterior probability (>...