A5090252960- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Glioma Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Cancer Immunotherapy and Biomarkers
- Molecular Biology Techniques and Applications
- Bacterial Genetics and Biotechnology
- DNA Repair Mechanisms
- interferon and immune responses
- Gene Regulatory Network Analysis
- RNA and protein synthesis mechanisms
- T-cell and B-cell Immunology
- Lung Cancer Treatments and Mutations
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Multiple Myeloma Research and Treatments
- Breast Cancer Treatment Studies
- Cancer Cells and Metastasis
- Endoplasmic Reticulum Stress and Disease
- Glycosylation and Glycoproteins Research
- Viral Infectious Diseases and Gene Expression in Insects
Washington University in St. Louis
2018-2023
James S. McDonnell Foundation
2018-2023
Baylor College of Medicine
2016-2019
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...
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 Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated treatment resistance, it remains unclear whether this diversity observed within metastases and to what extent cancer cell–intrinsic sculpts local immune microenvironment. Here, we profiled immunogenomic state 93 spatially distinct regions from 30...
Neoantigens are tumor-specific peptide sequences resulting from sources such as somatic DNA mutations. Upon loading onto major histocompatibility complex (MHC) molecules, they can trigger recognition by T cells. Accurate neoantigen identification is thus critical for both designing cancer vaccines and predicting response to immunotherapies. Neoantigen prioritization relies on correctly whether the presenting sequence successfully induce an immune response. Because most mutations...
Abstract Although endometrial cancer is the most common of female reproductive tract, we have little understanding what controls beyond transcriptional effects steroid hormones such as estrogen. As a result, limited therapeutic options for ~62,000 women diagnosed with each year in United States. Here, an attempt to identify new prognostic and targets, focused on area this cancer—alternative mRNA splicing—and investigated whether splicing factor, SF3B1, plays important role pathogenesis....
Freeze-frame synthetic proteins trap DNA reaction intermediates in single live cells, revealing origins of genome instability.
Abstract Circulating tumor DNA (ctDNA) in peripheral blood has been used to predict prognosis and therapeutic response for triple-negative breast cancer (TNBC) patients. However, previous approaches typically use large comprehensive panels of genes commonly mutated across all cancers. Given the reduction sequencing costs decreased turnaround times associated with panel generation, objective this study was assess custom micro-panels tracking disease predicting clinical outcomes patients TNBC....
ABSTRACT Microbes and human cells possess mechanisms of mutagenesis activated by stress responses. Stress-inducible may provide important models for that drives host-pathogen interactions, antibiotic resistance, possibly much evolution generally. In Escherichia coli , repair DNA double-strand breaks is switched to a mutagenic mode, using error-prone polymerases, via the SOS damage general (σ S ) We investigated small RNA (sRNA) clients Hfq, an chaperone promotes break (MBR), found GcvB MBR...
SUMMARY DNA damage provokes mutations and cancer, results from external carcinogens or endogenous cellular processes. Yet, the intrinsic instigators of are poorly understood. Here we identify proteins that promote when overproduced: DNA-damaging (DDPs). We discover a large network DDPs in Escherichia coli deconvolute them into six DNA-damage-causing function clusters, demonstrating DDP mechanisms three: reactive-oxygen increase by transmembrane transporters, chromosome loss replisome...
Abstract Background: While surgical resection of early stage cancers is often curative, a number patients will experience disease recurrence. Given the genomic heterogeneity cancer, we hypothesized that different driver mutations present in patient’s tumor may influence whether and when recurrence occurs. To investigate this, association between presence rates molecular residual (MRD) detection by circulating DNA (ctDNA) was evaluated with I-III colorectal cancer (CRC). Methods: This...
Abstract Neoantigens are novel peptide sequences resulting from sources such as somatic mutations in tumors. Upon loading onto major histocompatibility complex (MHC) molecules, they can trigger recognition by T cells. Accurate neoantigen identification is thus critical for both designing cancer vaccines and predicting response to immunotherapies. Neoantigen prioritization relies on correctly whether the presenting sequence successfully induce an immune response. As majority of single...
Abstract While the degree of spatial genomic heterogeneity within primary glioblastoma (GBM) has been previously investigated, extent this in other malignant brain tumors and its connection to local immune microenvironment remains unknown. To address this, we performed whole-exome, RNA, TCR sequencing on multiple spatially distinct sectors from a cohort comprised both metastases recurrent GBMs. Our results suggest striking difference which majority mutations predicted neoantigens are shared...
Abstract Purpose : Patients with triple negative breast cancer (TNBC) who do not achieve pathological complete response (pCR) following neoadjuvant chemotherapy have a high risk of recurrence and death. Molecular characterization may identify patients unlikely to pCR. This trial was conducted determine the pCR rate docetaxel carboplatin, molecular alterations and/or immune gene signatures predicting Experimental Design clinical stages II/III TNBC received 6 cycles carboplatin. The primary...
<div>Abstract<p>Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated treatment resistance, it remains unclear whether this diversity observed within metastases and to what extent cancer cell–intrinsic sculpts local immune microenvironment. Here, we profiled immunogenomic state 93 spatially distinct...
Supplementary Figure from Characterization of the Genomic and Immunologic Diversity Malignant Brain Tumors through Multisector Analysis