A5036126324- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- RNA modifications and cancer
- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- Genetic factors in colorectal cancer
- Molecular Biology Techniques and Applications
- Hepatocellular Carcinoma Treatment and Prognosis
- BRCA gene mutations in cancer
- Lung Cancer Treatments and Mutations
- Genetics, Bioinformatics, and Biomedical Research
- Genomics and Phylogenetic Studies
- Gene expression and cancer classification
- Hepatitis B Virus Studies
- Liver Disease Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Reproductive Health and Technologies
- Biological and pharmacological studies of plants
- Breast Cancer Treatment Studies
- Peptidase Inhibition and Analysis
- Lung Cancer Research Studies
- Genomics and Chromatin Dynamics
- Advanced Breast Cancer Therapies
- Protist diversity and phylogeny
- Endoplasmic Reticulum Stress and Disease
University of Utah
2024
James S. McDonnell Foundation
2016-2023
Washington University in St. Louis
2015-2022
Abstract Summary: Visualizing and summarizing data from genomic studies continues to be a challenge. Here, we introduce the GenVisR package addresses this challenge by providing highly customizable, publication-quality graphics focused on cohort level genome analyses. provides rapid easy-to-use suite of visualization tools, while maintaining high degree flexibility leveraging abilities ggplot2 Bioconductor. Availability Implementation: is an R available via Bioconductor...
Abstract Somatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools ( www.regtools.org ), a computationally efficient, free, open-source software package designed to integrate somatic variants from genomic data with splice junctions bulk or single cell transcriptomic identify cause aberrant splicing. We apply over 9000 tumor samples both DNA RNA sequence data. discovers...
Nearly all patients with small cell lung cancer (SCLC) eventually relapse chemoresistant disease. The molecular mechanisms driving chemoresistance in SCLC remain un-characterized. Here, we describe whole-exome sequencing of paired tumor samples procured at diagnosis and from 12 patients, unpaired 18 additional patients. Multiple somatic copy number alterations, including gains ABCC1 deletions MYCL, MSH2, MSH6, are identifiable relapsed samples. Relapse also exhibit recurrent mutations loss...
Here we report targeted sequencing of 83 genes using DNA from primary breast cancer samples 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation prognosis. Independent validation prognostic was achieved data the METABRIC study. Previously established associations MAP3K1 PIK3CA mutations with luminal A status/favorable prognosis TP53 Luminal B/non-luminal tumors/poor were observed,...
Following automated variant calling, manual review of aligned read sequences is required to identify a high-quality list somatic variants. Despite widespread use in analyzing sequence data, methods standardize have not been described, resulting high inter- and intralab variability.This standard operating procedure (SOP) consists annotate variants with four different calls 19 tags. The indicate reviewer's confidence each the tags commonly observed sequencing patterns artifacts that inform...
Abstract Somatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools ( www.regtools.org ), a computationally efficient, free, open-source software package designed to integrate somatic variants from genomic data with splice junctions bulk or single cell transcriptomic identify cause aberrant splicing. was applied over 9,000 tumor samples both DNA RNA sequence data. We...
Abstract Male infertility is associated with elevated rates of aneuploidy and DNA breaks in spermatozoa germline precursors. This common condition not well understood poor individual familial somatic health relative to fertile men. To further understand the extent source genome instability, we used error-corrected duplex sequencing test whether impaired spermatogenesis relatively poorer oligozoospermic men are linked single nucleotide de novo mutation frequencies their sperm blood,...
Mixed fibrolamellar hepatocellular carcinoma (mFL-HCC) is a rare liver tumor defined by the presence of both pure FL-HCC and conventional HCC components, represents up to 25% cases FL-HCC, has been associated with worse prognosis. Recent genomic characterization identified highly recurrent transcript fusion (DNAJB1:PRKACA) not found in HCC.We performed exome transcriptome sequencing case mFL-HCC. A novel BAC-capture approach was developed identify 400 kb deletion as underlying mechanism for...
Summary: Visualizing and summarizing data from genomic studies continues to be a challenge. Here we introduce the GenVisR package addresses this challenge by providing highly customizable, publication-quality graphics focused on cohort level genome analyses. provides rapid easy-to-use suite of visualization tools, while maintaining high degree flexibility leveraging abilities ggplot2 bioconductor. Availability Implementation: is an R available via bioconductor...
Osteosarcoma is a rare disease in children but one of the most common cancers adult large breed dogs. The mutational landscape both primary and pulmonary metastatic tumor two dogs with appendicular osteosarcoma (OSA) was comprehensively evaluated using an automated whole genome sequencing, exome RNA-seq pipeline that adapted for this study use Chromosomal lesions were type mutation. varied substantially between within same patient similar. Copy number neutral loss heterozygosity mutant TP53...
Abstract The interpretation of variants in cancer is frequently focused on direct protein coding alterations. However, most somatic mutations are noncoding regions the genome, and even exonic may have unidentified consequences. Here we present Regtools, a software package designed to efficiently identify that cause aberrant splicing tumors. Our tool integrates variant calls from genomic data with junctions extracted transcriptomic order examine potential cis alterations near variant. Based...
Abstract More than 50 genes are recurrently affected by somatic mutation in estrogen receptor positive (ER+) breast cancer but prognostic effects have not been definitively established. Primary tumor DNA was therefore subjected to targeted sequencing from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients. Independent validation of interactions achieved using independent data the METABRIC study. Associations between MAP3K1 PIK3CA...
Abstract Purpose Manual review of aligned sequencing reads is required to develop a high-quality list somatic variants from massively parallel data (MPS). Despite widespread use in analyzing MPS data, there has been little attempt describe methods for manual review, resulting high inter- and intra-lab variability variant detection characterization tumors. Methods Open source software was used an optimal method setup. We also developed systemic approach visually inspect each during review....
Abstract The interpretation of variants in cancer is often focused on genomic alterations that have a known coding consequence. This analysis strategy excludes somatic mutations non-coding regions the genome and even exonic may unidentified consequences. To address this issue, we created RegTools, free, open-source software package integrates variant calls from data with evidence expressed splice junctions transcriptomic to efficiently identify cause aberrant splicing tumors. date, applied...
Abstract Large-scale tumor sequencing projects, like The Cancer Genome Atlas (TCGA), have implicated thousands of somatic mutations in cancer. These initiatives incentivized many improvements variant detection. However, we observed that important pathogenic variants are often missed due to stringent filtering, heterogeneity, contamination normal, low purity, alignment challenges, and other issues. idiosyncrasies can impede detection algorithms from reliably calling even the most clinically...
Abstract Large-scale tumor sequencing projects, like The Cancer Genome Atlas (TCGA), have implicated thousands of somatic mutations in cancer. These initiatives incentivized many improvements variant detection. However, we observed that important pathogenic variants are often missed due to stringent filtering, heterogeneity, contamination normal, low purity, alignment challenges, and other issues. idiosyncrasies can impede detection algorithms from reliably calling even the most clinically...
Abstract Background- Triple negative breast cancer (TNBC) is the most aggressive subtype of as these patients have highest risk recurrence and death. Only 35% TNBC achieve a pathologic complete response (pCR) following neoadjuvant chemotherapy. Patients who do not pCR 27% distant ultimate death at 3 years compared to 9% for pCR. Unidentified micrometastases are responsible overt progression Developing strategies identify with minimal residual disease curative treatment an unmet need....