ArticlePacific Symposium on Biocomputing. Pacific Symposium on Biocomputing2016
REPURPOSING GERMLINE EXOMES OF THE CANCER GENOME ATLAS DEMANDS A CAUTIOUS APPROACH AND SAMPLE-SPECIFIC VARIANT FILTERING.
Article in Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- A comprehensive analysis of clinical and polygenic germline influences on somatic mutational burden.American journal of human genetics · 2024Article
- A method to delineate de novo missense variants across pathways prioritizes genes linked to autism.Science translational medicine · 2021Article
- Harnessing the paradoxical phenotypes of APOE ɛ2 and APOE ɛ4 to identify genetic modifiers in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Impact of variant-level batch effects on identification of genetic risk factors in large sequencing studies.PloS one · 2021Article
- Germline genomic patterns are associated with cancer risk, oncogenic pathways, and clinical outcomes.Science advances · 2020Article
- CAGI5: Objective performance assessments of predictions based on the Evolutionary Action equation.Human mutation · 2019Article
- Substantial batch effects in TCGA exome sequences undermine pan-cancer analysis of germline variants.BMC cancer · 2019Article
- The Germline Variants rs61757955 and rs34988193 Are Predictive of Survival in Lower Grade Glioma Patients.Molecular cancer research : MCR · 2019Article
- Comprehensive Genomic Characterization of Parathyroid Cancer Identifies Novel Candidate Driver Mutations and Core Pathways.Journal of the Endocrine Society · 2019Article
- Article
- A framework for the estimation of the proportion of true discoveries in single nucleotide variant detection studies for human data.PloS one · 2018Article
- Objective assessment of the evolutionary action equation for the fitness effect of missense mutations across CAGI-blinded contests.Human mutation · 2017Review
- Article
- METHODS TO ENHANCE THE REPRODUCIBILITY OF PRECISION MEDICINE.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
When seeking to reproduce results derived from whole-exome or genome sequencing data that could advance precision medicine, the time and expense required to produce a patient cohort make data repurposing an attractive option. The first step in repurposing is setting some quality baseline for the data so that conclusions are not spurious. This is difficult because there can be variations in quality from center to center, clinic to clinic and even patient to patient. Here, we assessed the quality of the whole-exome germline mutations of TCGA cancer patients using patterns of nucleotide substitution and negative selection against impactful mutations. We estimated the fraction of false positive variant calls for each exome with respect to two gold standard germline exomes, and found large variability in the quality of SNV calls between samples, cancer subtypes, and institutions. We then demonstrated how variant features, such as the average base quality for reads supporting an allele, can be used to identify sample-specific filtering parameters to optimize the removal of false positive calls. We concluded that while these germlines have many potential applications to precision medicine, users should assess the quality of the available exome data prior to use and perform additional filtering steps.
Indexed as
Identifiers
26776187PMC4720392What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.