A5039487615- Cancer Genomics and Diagnostics
- BRCA gene mutations in cancer
- RNA Research and Splicing
- Genetic factors in colorectal cancer
- Gene expression and cancer classification
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Radioactivity and Radon Measurements
- Data-Driven Disease Surveillance
- Molecular Biology Techniques and Applications
- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Colorectal Cancer Treatments and Studies
- Genomics and Rare Diseases
- Radioactive contamination and transfer
- Radiation Dose and Imaging
- Effects of Radiation Exposure
- Carcinogens and Genotoxicity Assessment
- Bioinformatics and Genomic Networks
- COVID-19 epidemiological studies
- Spatial and Panel Data Analysis
- Genomic variations and chromosomal abnormalities
- Respiratory viral infections research
- Radiation Therapy and Dosimetry
Western University
2014-2023
Cytodiagnostics (Canada)
2021-2022
Washington Center
2016
University of Washington
2016
University of Windsor
2008
Abstract The selection of effective genes that accurately predict chemotherapy responses might improve cancer outcomes. We compare optimized gene signatures for cisplatin, carboplatin, and oxaliplatin in the same cell lines validate each signature using data from patients with cancer. Supervised support vector machine learning is used to derive sets whose expression related line GI 50 values by backwards feature cross-validation. Specific functional pathways distinguishing sensitive...
<ns4:p>The interpretation of genomic variants has become one the paramount challenges in post-genome sequencing era. In this review we summarize nearly 20 years research on applications information theory (IT) to interpret coding and non-coding mutations that alter mRNA splicing rare common diseases. We compile spectrum published analyzed by IT, provide a broad perspective distribution deleterious natural cryptic splice site detected, as well those affecting regulatory sequences. Results for...
Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial remain unexplained. To determine whether some missing heritability is due to rare variants conferring high moderate risk, we tested for an association between c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 FANCM gene and cancer. An analysis genotyping data from 8635 cases 6625 controls different countries yielded [odds ratio (OR) = 3.93 (95%...
Formalin-fixed paraffin embedded (FFPE) samples are challenging to profile using existing high-throughput sequencing technologies, including RNA-seq. This difficulty primarily arises from the degradation of nucleic acids, a problem that becomes particularly acute with stored for extended periods. FFPE-derived RNA-seq (fRNA-seq) data have high rate transcript dropout, property shared single cell Transcript counts also variance and prone extreme values. We introduce PaRaffin Embedded...
Ductal Carcinoma in Situ (DCIS) management is challenged by the absence of reliable markers predictive radiotherapy (RT) response, leading to both overtreatment indolent disease and inadequate treatment for aggressive cases. Through whole-exome sequencing 147 DCIS cases, we characterized genomic landscape identified prognosis - specifically risk local recurrence (in situ or invasive) within 10 years after diagnosis. Our analysis revealed that pure frequent mutations genes governing tissue...
Mutations that affect mRNA splicing often produce multiple isoforms, resulting in complex molecular phenotypes. Definition of an exon and its inclusion mature relies on joint recognition both acceptor donor splice sites. This study predicts cryptic exon-skipping isoforms produced by mutations from the combined information contents (Ri, which measures binding-site strength, bits) distribution sites defining these exons. The total content (Ri,total) is sum Ri values sites, adjusted for...
BRCA1 and BRCA2 testing for hereditary breast ovarian cancer (HBOC) does not identify all pathogenic variants. Sequencing of 20 complete genes in HBOC patients with uninformative test results (N = 287), including noncoding flanking sequences ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51B, STK11, TP53, XRCC2, identified 38,372 unique We apply information theory (IT) to predict prioritize variants uncertain significance regulatory,...
<ns4:p>Genomic aberrations and gene expression-defined subtypes in the large METABRIC patient cohort have been used to stratify predict survival. The present study normalized expression signatures of paclitaxel drug response outcome for different survival times patients receiving hormone (HT) and, some cases, chemotherapy (CT) agents. This machine learning method, which distinguishes sensitivity vs. resistance breast cancer cell lines validates predictions patients; was also derive other HT...
Sequencing of both healthy and disease singletons yields many novel low frequency variants uncertain significance (VUS). Complete gene genome sequencing by next generation (NGS) significantly increases the number VUS detected. While prior studies have emphasized protein coding variants, non-coding sequence also been proven to contribute high penetrance disorders, such as hereditary breast ovarian cancer (HBOC). We present a strategy for analyzing different functional classes based on...
Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE peak datasets 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating need to compensate for skewed nucleotide composition, distinguishes true motifs noise, quantifies strengths individual sites computed affinity detects adjacent cofactor that...
Splice isoform structure and abundance can be affected by either non-coding or masquerading coding variants that alter the of transcripts. When these are common in population, non-constitutive transcripts sufficiently frequent so as to resemble naturally occurring, alternative mRNA splicing. Prediction effects such has been shown accurate using information theory-based methods. Single nucleotide polymorphisms (SNPs) predicted significantly natural and/or cryptic splice site strength were...
hYVH1 [human orthologue of YVH1 (yeast VH1-related phosphatase)] is an atypical dual-specificity phosphatase that widely conserved throughout evolution. Deletion studies in yeast have suggested a role for this regulating cell growth. However, the human unknown. The present study used MS to identify Hsp70 (heat-shock protein 70) as novel hYVH1-binding partner. interaction was confirmed using endogenous co-immunoprecipitation experiments and direct binding purified proteins. Endogenous...
Variants of uncertain significance (VUS) in the BRCA1 and BRCA2 genes potentially affecting coding sequence as well normal splicing activity have confounded predisposition testing breast cancer. Here, we apply information theory to analyze BRCA1/2 mRNA mutations categorized VUS. The method was validated for 31 36 known cause missplicing all 26 that do not alter splicing. All single-nucleotide variants Breast Cancer Information Resource (BIC; Core Database; http://research.nhgri.nih.gov/bic;...
Abstract Information theory-based methods have been shown to be sensitive and specific for predicting quantifying the effects of non-coding mutations in Mendelian diseases. We present Shannon pipeline software genome-scale mutation analysis provide evidence that predicts variants affecting mRNA splicing. Individual information contents (in bits) reference variant splice sites are compared significant differences annotated prioritized. The has implemented CLC-Bio Genomics platform. Annotation...
<ns3:p><ns3:bold>Background:</ns3:bold> Gene signatures derived from transcriptomic data using machine learning methods have shown promise for biodosimetry testing. These may not be sufficiently robust large scale testing, as their performance has been adequately validated on external, independent datasets. The present study develops human and murine with biochemically-inspired that are strictly k-fold traditional approaches.</ns3:p><ns3:p> <ns3:bold>Methods:</ns3:bold> Expression Omnibus...
<ns4:p>The interpretation of genomic variants has become one the paramount challenges in post-genome sequencing era. In this review we summarize nearly 20 years research on applications information theory (IT) to interpret coding and non-coding mutations that alter mRNA splicing rare common diseases. We compile spectrum published analyzed by IT, provide a broad perspective distribution deleterious natural cryptic splice site detected, as well those affecting regulatory sequences. Results for...
The widespread use of next generation sequencing for clinical testing is detecting an escalating number variants in noncoding regions the genome. significance majority these currently unknown, which presents a significant challenge. We have screened over 6,000 early-onset and/or familial breast cancer (BC) cases collected by ENIGMA consortium sequence 5′ BC susceptibility genes BRCA1 and BRCA2, identified 141 rare with global minor allele frequency < 0.01, 76 not been reported previously....
<ns4:p>Genomic aberrations and gene expression-defined subtypes in the large METABRIC patient cohort have been used to stratify predict survival. The present study normalized expression signatures of paclitaxel drug response outcome for different survival times patients receiving hormone (HT) and, some cases, chemotherapy (CT) agents. This machine learning method, which distinguishes sensitivity vs. resistance breast cancer cell lines validates predictions patients, was also derive other HT...
<ns3:p><ns3:bold>Background:</ns3:bold>Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear bound replicating sequences.</ns3:p><ns3:p><ns3:bold>Methods:</ns3:bold>Information theory-based analysis interactions between RBPs and individual sequences the Severe Acute Respiratory Syndrome CoronaVirus 2...
Background Accurate radiation dose estimates are critical for determining eligibility therapies by timely triaging of exposed individuals after large-scale events. However, the universal assessment a large population subjected to nuclear spill incident or detonation is not feasible. Even with high-throughput dosimetry analysis, test volumes far exceed capacities first responders measure exposures directly, acquire and process samples follow-on biodosimetry testing. Aim To significantly...
<ns4:p><ns4:bold>Background:</ns4:bold> Gene signatures derived from transcriptomic data using machine learning methods have shown promise for biodosimetry testing. These may not be sufficiently robust large scale testing, as their performance has been adequately validated on external, independent datasets. The present study develops human and murine with biochemically-inspired that are strictly k-fold traditional approaches.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> Expression Omnibus...
Background: Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear bound replicating sequences. Methods: Information theory-based analysis interactions between RBPs and individual sequences the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N1), HIV-1, Dengue genomes...
<ns4:p>We present a major public resource of mRNA splicing mutations validated according to multiple lines evidence abnormal gene expression. Likely in all tumor types reported the Cancer Genome Atlas (TCGA) were identified based on comparative strengths splice sites versus normal genomes, and then by respectively comparing counts junction spanning abundance transcript reads RNA-Seq data from matched tissues tumors lacking these mutations. The comprehensive features 351,423 mutations,...