ArticlePloS one2018
Whole-exome sequencing capture kit biases yield false negative mutation calls in TCGA cohorts.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
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- CCDC154 knockdown inhibits growth of liver cancer via suppressing expression of Snail.European journal of medical research · 2025Article
- Comparative evaluation of four exome enrichment solutions in 2024: Agilent, Roche, Vazyme and Nanodigmbio.BMC genomics · 2025Article
- Determinants of gastric cancer immune escape identified from non-coding immune-landscape quantitative trait loci.Nature communications · 2024Article
- Association of tumor immune infiltration and prognosis with homologous recombination repair genes mutations in early triple-negative breast cancer.Frontiers in immunology · 2024Article
- Transcriptome analysis of peripheral blood of Schistosoma mansoni infected children from the Albert Nile region in Uganda reveals genes implicated in fibrosis pathology.PLoS neglected tropical diseases · 2023Article
- Whole-exome sequencing of rectal neuroendocrine tumors.Endocrine-related cancer · 2023Article
- Genomic and immune characteristics of HER2-mutated non-small-cell lung cancer and response to immune checkpoint inhibitor-based therapy.Molecular oncology · 2023Article
- Deep learning image analysis quantifies tumor heterogeneity and identifies microsatellite instability in colon cancer.Journal of surgical oncology · 2023Article
- Fast, accurate, and racially unbiased pan-cancer tumor-only variant calling with tabular machine learning.NPJ precision oncology · 2023Article
- A Genomically and Clinically Annotated Patient-Derived Xenograft Resource for Preclinical Research in Non-Small Cell Lung Cancer.Cancer research · 2022Article
- The genomic landscape of pediatric renal cell carcinomas.iScience · 2022Article
- MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil.Frontiers in immunology · 2022Article
- Coiled-Coil Domain-Containing (CCDC) Proteins: Functional Roles in General and Male Reproductive Physiology.Reproductive sciences (Thousand Oaks, Calif.) · 2021Review
- Deep sequencing of pre-translational mRNPs reveals hidden flux through evolutionarily conserved alternative splicing nonsense-mediated decay pathways.Genome biology · 2021Article
- A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency.Genome biology · 2021Article
- Impact of variant-level batch effects on identification of genetic risk factors in large sequencing studies.PloS one · 2021Article
- Methodological differences can affect sequencing depth with a possible impact on the accuracy of genetic diagnosis.Genetics and molecular biology · 2020Article
- Computational Prediction and Validation of Tumor-Associated Neoantigens.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The Cancer Genome Atlas (TCGA) provides a genetic characterization of more than ten thousand tumors, enabling the discovery of novel driver mutations, molecular subtypes, and enticing drug targets across many histologies. Here we investigated why some mutations are common in particular cancer types but absent in others. As an example, we observed that the gene CCDC168 has no mutations in the stomach adenocarcinoma (STAD) cohort despite its common presence in other tumor types. Surprisingly, we found that the lack of called mutations was due to a systematic insufficiency in the number of sequencing reads in the STAD and other cohorts, as opposed to differential driver biology. Using strict filtering criteria, we found similar behavior in four other genes across TCGA cohorts, with each gene exhibiting systematic sequencing depth issues affecting the ability to call mutations. We identified the culprit as the choice of exome capture kit, as kit choice was highly associated with the set of genes that have insufficient reads to call a mutation. Overall, we found that thousands of samples across all cohorts are subject to some capture kit problems. For example, for the 6353 samples using the Broad Institute's Custom capture kit there are undercalling biases for at least 4833 genes. False negative mutation calls at these genes may obscure biological similarities between tumor types and other important cancer driver effects in TCGA datasets.
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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.