William Phu
A5085065389- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Genomics and Phylogenetic Studies
- Genetic Associations and Epidemiology
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Genetic factors in colorectal cancer
- MicroRNA in disease regulation
- Neurogenesis and neuroplasticity mechanisms
Boston Children's Hospital
2021-2024
Broad Institute
2021-2024
Massachusetts General Hospital
2021-2024
Harvard University
2021-2022
Institut thématique Génétique, génomique et bioinformatique
2021
Massachusetts Institute of Technology
2020
Whitehead Institute for Biomedical Research
2020
Abstract The depletion of disruptive variation caused by purifying natural selection (constraint) has been widely used to investigate protein-coding genes underlying human disorders, but attempts assess constraint for non-protein-coding regions have proven more difficult. Here we aggregate, process, and release a dataset 76,156 genomes from the Genome Aggregation Database (gnomAD), largest public open-access genome reference dataset, use this build mutational map whole genome. We present...
Exome and genome sequencing have become the tools of choice for rare disease diagnosis, leading to large amounts data available analyses. To identify causal variants in these datasets, powerful filtering decision support that can be efficiently used by clinicians researchers are required. address this need, we developed seqr - an open-source, web-based tool family-based monogenic analysis allows work collaboratively search annotate genomic callsets. date, is being several research pipelines...
Multiple sclerosis (MS) is an autoimmune disease characterized by attack on oligodendrocytes within the central nervous system (CNS). Despite widespread use of immunomodulatory therapies, patients may still face progressive disability because failure myelin regeneration and loss neurons, suggesting additional cellular pathologies. Here, we describe a general approach for identifying specific cell types in which allele exerts pathogenic effect. Applying this to MS risk loci, pinpoint likely...
Summary Genome organization is intricately tied to regulating genes and associated cell fate decisions. Here, we examine the positioning functional significance of human genes, grouped by their lineage restriction level, within 3D genome. We reveal that different levels have distinct relationships with both domains loop anchors, remarkably consistent boundaries across types. While associations each group are primarily type-specific, conserved maintain greater stability genomic features...
Abstract Missense variants can have a range of functional impacts depending on factors such as the specific amino acid substitution and location within gene. To interpret their deleteriousness, studies sought to identify regions genes that are specifically intolerant missense variation 1–12 . Here, we leverage patterns rare in 125,748 individuals Genome Aggregation Database (gnomAD) 13 against null mutational model transcripts display regional differences constraint. Missense-depleted...
Abstract Exome and genome sequencing have become the tools of choice for rare disease diagnosis, leading to large amounts data available analyses. To identify causal variants in these datasets, powerful filtering decision support that can be efficiently used by clinicians researchers are required. address this need, we developed seqr - an open source, web-based tool family-based monogenic analysis allows work collaboratively search annotate genomic callsets. date, is being several research...
ABSTRACT The precise regulation of gene expression is fundamental to neurodevelopment, plasticity, and cognitive function. While several studies have deeply profiled mRNA dynamics in the developing human brain, there a gap our understanding accompanying translational regulation. We perform ribosome profiling from more than 70 prenatal adult cortex samples across ontogeny into adulthood, mapping translation events at nucleotide resolution. In addition characterizing annotated open reading...