Benjamin J. Strober
A5059094748- Genetic Associations and Epidemiology
- RNA Research and Splicing
- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- Genomics and Rare Diseases
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Genetic Mapping and Diversity in Plants and Animals
- Gene Regulatory Network Analysis
- Telomeres, Telomerase, and Senescence
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
- Genetic factors in colorectal cancer
- RNA and protein synthesis mechanisms
- Gene expression and cancer classification
- Epigenetics and DNA Methylation
- Genomic variations and chromosomal abnormalities
- Molecular Biology Techniques and Applications
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Insect Resistance and Genetics
- Kruppel-like factors research
- Genetics, Aging, and Longevity in Model Organisms
- Viral Infectious Diseases and Gene Expression in Insects
- Polyomavirus and related diseases
Harvard University
2022-2025
Johns Hopkins University
2015-2023
Harvard University Press
2023
Johns Hopkins Medicine
2022-2023
University of Chicago
2022
Thermo Fisher Scientific (Sweden)
2020
Princeton University
2019
Dana-Farber Cancer Institute
2017
National Institutes of Health
1990
National Cancer Institute
1990
The Genotype-Tissue Expression (GTEx) project dissects how genetic variation affects gene expression and splicing.
Abstract Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy general robustness misspecified reference sets. We apply this framework 44 GTEx tissues 100+ from GWAS meta-analysis studies, creating growing public catalog of associations seeks capture the effects variation on human...
Telomere length within an individual varies in a correlated manner across most tissues.
Abstract Rare genetic variants are abundant in humans and expected to contribute individual disease risk 1,2,3,4 . While association studies have successfully identified common associated with susceptibility, these not practical for identifying rare 1,5 Efforts distinguish pathogenic from benign leveraged the code identify deleterious protein-coding alleles 1,6,7 , but no analogous exists non-coding variants. Therefore, ascertaining which phenotypic effects remains a major challenge. been...
Abstract The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues, and link these regulatory mechanisms trait disease associations. Here, we present analyses of v8 data, based 17,382 RNA-sequencing samples from 54 tissues 948 post-mortem donors. We comprehensively associations for gene expression splicing in cis trans , showing that are found almost all genes, describe underlying molecular their contribution...
Variants affect gene expression over time Genetic variation drives the spectrum of human phenotypes but in some cases has been linked to pathological conditions. Strober et al. set out explore how genetic diversity regulates cell differentiation time. They examined quantitative trait loci (eQTLS)—genetic variants correlated with expression—in induced pluripotent stem lines from 19 Yoruban individuals at 16 points during into cardiomyocytes. identified hundreds developmental stage–specific...
Outliers in the human transcriptome reveal functional effects of rare genetic variants.
Abstract Allele expression (AE) analysis robustly measures cis -regulatory effects. Here, we present and demonstrate the utility of a vast AE resource generated from GTEx v8 release, containing 15,253 samples spanning 54 human tissues for total 431 million measurements at SNP level 153 haplotype level. In addition, develop an extension our tool phASER that allows effect sizes variants to be estimated using haplotype-level data. This is largest date, are able make data publicly available. We...
Merkel cell carcinoma (MCC) frequently contains integrated copies of polyomavirus DNA that express a truncated form Large T antigen (LT) and an intact Small (ST). While LT binds RB inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show specifically the MYC homolog MYCL (L-MYC) recruits 15-component EP400 histone acetyltransferase chromatin remodeling complex. We performed large-scale immunoprecipitation for identified...
Dynamic and temporally specific gene regulatory changes may underlie unexplained genetic associations with complex disease. During a dynamic process such as cellular differentiation, the overall cell type composition of tissue (or an in vitro culture) profile each can both experience significant over time. To identify these effects high resolution, we collected single-cell RNA-sequencing data differentiation time course from induced pluripotent stem cells to cardiomyocytes, sampled at 7...
Uncovering the functional impact of genetic variation on gene expression is important in understanding tissue biology and pathogenesis complex traits. Despite large efforts to map quantitative trait loci (eQTLs) across many human tissues, our ability translate those findings disease has been incomplete, majority are not explained by association with a target gene. Cell-type specificity presence multiple independent causal variants for eQTLs potential confounders contributing apparent...
A sensitive exonuclease assay revealed multiple sites for interaction, in vitro, of sequence specific factors with c-myc upstream elements. At one site, more than 1500 base pairs the promoter P1, binding activity was lost as dimethyl sulfoxide (Me2SO) induced shut-off expression HL-60 and U-937 leukemia cells. The disappearance other activities not noted. In addition, noted to be cell-line specific. Me2SO-regulated factor precisely located allowing confirmation temporal pattern regulation by...
Abstract Expression quantitative trait locus (eQTL) mapping provides a powerful means to identify functional variants influencing gene expression and disease pathogenesis. We report the identification of cis-eQTLs from 7,051 post-mortem samples representing 44 tissues 449 individuals as part Genotype-Tissue (GTEx) project. find cis-eQTL for 88% all annotated protein-coding genes, with one-third having multiple independent effects. numerous tissue-specific cis-eQTLs, highlighting unique...
Abstract Genetic regulation of gene expression is a complex process, with genetic effects known to vary across cellular contexts such as cell types and environmental conditions. We developed SURGE, method for unsupervised discovery context-specific quantitative trait loci (eQTLs) from single-cell transcriptomic data. This allows the or modulating without prior knowledge. Applied peripheral blood eQTL data, SURGE capture continuous representations distinct groupings biologically related...
Abstract Differential allele-specific expression (ASE) is a powerful tool to study context-specific cis-regulation of gene expression. Such effects can reflect the interaction between genetic or epigenetic factors and measured context condition. Single-cell RNA sequencing (scRNA-seq) allows measurement ASE at individual-cell resolution, but there lack statistical methods analyze such data. We present Allelic Expression using Single-Cell data (DAESC), method for differential analysis...
Practically all studies of gene expression in humans to date have been performed a relatively small number adult tissues. Gene regulation is highly dynamic and context-dependent. In order better understand the connection between complex phenotypes, including disease, we need be able study more cell types, tissues, states that are relevant human phenotypes. particular, characterize early development as mutations affect developmental processes may particular relevance traits. To address this...
Each human genome has tens of thousands rare genetic variants; however, identifying impactful variants remains a major challenge. We demonstrate how use personal multi-omics can enable identification by using the Multi-Ethnic Study Atherosclerosis, which included several hundred individuals, with whole-genome sequencing, transcriptomes, methylomes, and proteomes collected across two time points, 10 years apart. evaluated each phenotype's ability to separately jointly inform functional...
Abstract Rare genetic variation is abundant in the human genome, yet identifying functional rare variants and their impact on traits remains challenging. Measuring aberrant gene expression has aided functional, large-effect variants. Here, we expand detection of genetically driven transcriptome abnormalities by evaluating integrating expression, allele-specific alternative splicing from multi-tissue RNA-sequencing data. We demonstrate that each signal informs unique classes further develop...
Abstract Leveraging data from multiple ancestries can greatly improve fine-mapping power due to differences in linkage disequilibrium and allele frequencies. We propose MultiSuSiE, an extension of the sum single effects model (SuSiE) that allows causal effect sizes vary across based on a multivariate normal prior informed by empirical data. evaluated MultiSuSiE via simulations analyses 14 quantitative traits leveraging whole-genome sequencing 47k African-ancestry 94k European-ancestry...