Genome measures used for quality control are dependent on gene function and ancestry
Open accessAbstract
MOTIVATION: The transition/transversion (Ti/Tv) ratio and heterozygous/nonreference-homozygous (het/nonref-hom) ratio have been commonly computed in genetic studies as a quality control (QC) measurement. Additionally, these two ratios are helpful in our understanding of the patterns of DNA sequence evolution. RESULTS: To thoroughly understand these two genomic measures, we performed a study using 1000 Genomes Project (1000G) released genotype data (N=1092). An additional two datasets (N=581 and N=6) were used to validate our findings from the 1000G dataset. We compared the two ratios among continental ancestry, genome regions and gene functionality. We found that the Ti/Tv ratio can be used as a quality indicator for single nucleotide polymorphisms inferred from high-throughput sequencing data. The Ti/Tv ratio varies greatly by genome region and functionality, but not by ancestry. The het/nonref-hom ratio varies greatly by ancestry, but not by genome regions and functionality. Furthermore, extreme guanine + cytosine content (either high or low) is negatively associated with the Ti/Tv ratio magnitude. Thus, when performing QC assessment using these two measures, care must be taken to apply the correct thresholds based on ancestry and genome region. Failure to take these considerations into account at the QC stage will bias any following analysis. CONTACT: yan.guo@vanderbilt.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Repeating the analyses using only transversion SNPs found no indication of systematic bias in the Sidon individuals' genetic patterns.
“To test this, we repeated the analyses using only transversion SNPs, which are less prone to characteristic ancient DNA errors, but found no indication of systematic bias (Wang et al., 2015).”
From The Genomic History of the Bronze Age Southern Levant (2020) · cites this paper as Wang et al., 2015
The Introduction defines transversion SNPs, and the Discussion describes transition/transversion ratios as a sequencing quality-control measure. Neither section addresses characteristic ancient-DNA errors or Sidon individuals. The repeated analysis and its finding of no systematic bias are presented in the citing sentence as the citing authors’ own work, not Wang et al.’s. (LLM, conf=0.78)
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- Authors
- Wang, J., Raskin, L., Samuels, D. C., Shyr, Y., & Guo, Y.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Shyr, Yu
- Guo, Yan
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-10-08
- Volume
- 31
- Issue
- 3
- Pages
- 318-323
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- PMC
- PMC4308666
- OpenAlex
- W2127495773
- Cited by
- 173
- References
- 22
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 15 · 2023: 18 · 2022: 19 · 2021: 28 · 2020: 26 · 2019: 15 · 2018: 11 · 2017: 9 · 2016: 3 · 2015: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Bioinformatics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P30 CA 68485, R01CA125558, R01CA148667, U01CA163056, R01CA118229, R01CA64266, R00CA158141, R01CA158473, P30CA068485)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- genotype quality control, transition/transversion ratio, single nucleotide polymorphisms, 1000 Genomes Project, continental ancestry, gene function, genomic regions, GC content, DNA sequence evolution, sequencing data quality
- MeSH terms
- Genotype, Humans, Phenotype, Quality Control, Genome, Human, Evolution, Molecular, Polymorphism, Single Nucleotide, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing
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