A5005690333- Epigenetics and DNA Methylation
- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- Silicon and Solar Cell Technologies
- Mechanisms of cancer metastasis
- Genetic Syndromes and Imprinting
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- Genetic Associations and Epidemiology
- Gene expression and cancer classification
- Cancer-related molecular mechanisms research
- Silicon Carbide Semiconductor Technologies
- Renal cell carcinoma treatment
- Genomics and Chromatin Dynamics
- Gene Regulatory Network Analysis
- Bioinformatics and Genomic Networks
- Prenatal Screening and Diagnostics
- Plant Virus Research Studies
- Bacteriophages and microbial interactions
- RNA Research and Splicing
- Polyomavirus and related diseases
- Statistical Methods and Inference
- Health Systems, Economic Evaluations, Quality of Life
- Cancer-related gene regulation
- FOXO transcription factor regulation
University of British Columbia
2020-2025
British Columbia Children's Hospital
2020-2025
Dana-Farber Cancer Institute
2015-2021
Harvard University
2015-2021
University of Wisconsin–Madison
2014-2019
UW Health University Hospital
2011
In high-throughput studies, hundreds to millions of hypotheses are typically tested. Statistical methods that control the false discovery rate (FDR) have emerged as popular and powerful tools for error control. While classic FDR use only p values input, more modern been shown increase power by incorporating complementary information informative covariates prioritize, weight, group hypotheses. However, there is currently no consensus on how compare one another. We investigate accuracy,...
The ability to quantify cellular heterogeneity is a major advantage of single-cell technologies. However, statistical methods often treat as nuisance. We present novel method characterize differences in expression the presence distinct states within and among biological conditions. demonstrate that this framework can detect differential patterns under wide range settings. Compared existing approaches, has higher power subtle gene distributions are more complex than mean shift, those...
Abstract Lineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism adaptive resistance targeted therapy in cancer. An archetypal example development neuroendocrine prostate cancer (NEPC) after treatment adenocarcinoma (PRAD) with inhibitors androgen signaling. NEPC aggressive variant that aberrantly expresses genes characteristic (NE) tissues and no longer depends on androgens. Here, we investigate epigenomic basis this by profiling histone...
With recent advances in sequencing technology, it is now feasible to measure DNA methylation at tens of millions sites across the entire genome. In most applications, biologists are interested detecting differentially methylated regions, composed multiple with differing levels among populations. However, current computational approaches for such regions do not provide accurate statistical inference. A major challenge reporting uncertainty that a genome-wide scan involved these which needs be...
Resource15 January 2018Open Access Transparent process High-throughput identification of RNA nuclear enrichment sequences Chinmay J Shukla Department Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA Broad Institute MIT Harvard, Biostatistics Computational Dana-Farber Cancer Institute, Boston, Program in Biological Biomedical Sciences, Medical School, Search for more papers by this author Alexandra L McCorkindale Berlin Systems Max Delbrück Center Molecular Medicine,...
Androgen receptor (AR) in prostate cancer (PCa) can drive transcriptional repression of multiple genes including MYC, and supraphysiological androgen is effective some patients. Here, we show that this independent AR chromatin binding driven by coactivator redistribution, through conformation capture methods disruption the interaction between MYC super-enhancer within PCAT1 gene promoter. Conversely, deprivation vitro vivo increases expression. In parallel, global activity suppressed...
Neuroendocrine prostate cancer (NEPC) is a resistance phenotype that emerges in men with metastatic castration-resistant adenocarcinoma (CR-PRAD) and has important clinical implications, but challenging to detect practice. Herein, we report novel tissue-informed epigenetic approach noninvasively NEPC.
Chromosomal copy number alterations (CNAs) and human papillomavirus (HPV) DNA integration into the host genome are more frequent in invasive cervical cancers compared to precancers.However, relationship between CNAs viral is not well understood.We analyzed chromosomal HPV 17 biopsies from women diagnosed with intraepithelial neoplasia grade 3 (CIN3) 21 carcinoma.All samples were HPV16-positive.HPV was evaluated by sequencing of chimeric transcripts or hybrid capture reads.Chromosomal...
Cancers avoid immune surveillance through an array of mechanisms, including perturbation HLA class I antigen presentation. Merkel cell carcinoma (MCC) is aggressive, HLA-I-low, neuroendocrine the skin often caused by polyomavirus (MCPyV). Through characterization 11 newly generated MCC patient-derived lines, we identified transcriptional suppression several presentation genes. To systematically identify regulators HLA-I loss in MCC, performed parallel, genome-scale, gain- and...
Human populations have substantial genetic diversity, but the extent of epigenetic diversity remains unclear, as population-specific DNA methylation (DNAm) has only been studied for ~3.0% CpGs. This study quantifies DNAm using whole-genome bisulfite sequencing (WGBS) and analyzes it alongside genotype data to reveal a comprehensive picture DNAm. Using 'co-methylated region' (CMR) approach, 36,657 CMRs were identified in 62 lymphoblastoid B cell line (LCL) WGBS samples, with validation array...
Abstract Motivation: Identifying and prioritizing somatic mutations is an important challenging area of cancer research that can provide new insights into gene function as well targets for drug development. Most methods rely primarily on frequency-based criteria, where a identified having driver mutation if it altered in significantly more samples than expected according to background model. Although useful, are limited all treated equally. It known, however, some have no functional...
Summary With recent advances in sequencing technology, it is now feasible to measure DNA methylation at tens of millions sites across the entire genome. In most applications, biologists are interested detecting differentially methylated regions, composed multiple with differing levels among populations. However, current computational approaches for such regions do not provide accurate statistical inference. A major challenge reporting uncertainty that a genome-wide scan involved these which...
Abstract Background The recently launched DNA methylation profiling platform, Illumina MethylationEPIC BeadChip Infinium microarray v2.0 (EPICv2), is highly correlated with measurements obtained from its predecessor v1.0 (EPICv1). However, the concordance between two versions in context of methylation-based tools, including cell type deconvolution algorithms, epigenetic clocks, and inflammation lifestyle biomarkers has not yet been investigated. To address this, we profiled on both EPIC...
ABSTRACT Genetic Analysis Workshop 18 provided whole‐genome sequence data in a pedigree‐based sample and longitudinal phenotype for hypertension related traits, presenting an excellent opportunity evaluating analysis choices. We summarize the nine contributions to working group on collapsing methods, which evaluated various approaches of multiple rare variants. One contributor defined variant prioritization scheme, whereas remaining eight contributors statistical methods association...
Abstract Background In high-throughput studies, hundreds to millions of hypotheses are typically tested. Statistical methods that control the false discovery rate (FDR) have emerged as popular and powerful tools for error control. While classic FDR use only p -values input, more modern been shown increase power by incorporating complementary information “informative covariates” prioritize, weight, group hypotheses. However, there is currently no consensus on how compare one another. We...
Abstract The scientific community is increasingly embracing open science. This growing commitment to science should be applauded and encouraged, especially when it occurs voluntarily prior peer review. Thanks other researchers’ dedication science, we have had the privilege of conducting a reanalysis landmark experiment published as preprint with data made available in public repository. study question found that promoter DNA methylation frequently insufficient induce transcriptional...
Scope Polyphenols from the phytoestrogen group, including pterostilbene (PTS), are known for their antioxidant, anti‐inflammatory, and anti‐cancer effects. In recent reports, phytoestrogens attenuate age‐related diseases; however, pro‐longevity effects in healthy models mammals remain unknown. As longevity research demonstrates transcriptomic signatures human blood, current study hypothesizes that phytoestrogen‐supplemented diet may induce changes gene expression ultimately confer benefits....