|Title||Assessing reproducibility of inherited variants detected with short-read whole genome sequencing.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Pan, B, Ren, L, Onuchic, V, Guan, M, Kusko, R, Bruinsma, S, Trigg, L, Scherer, A, Ning, B, Zhang, C, Glidewell-Kenney, C, Xiao, C, Donaldson, E, Sedlazeck, FJ, Schroth, G, Yavas, G, Grunenwald, H, Chen, H, Meinholz, H, Meehan, J, Wang, J, Yang, J, Foox, J, Shang, J, Miclaus, K, Dong, L, Shi, L, Mohiyuddin, M, Pirooznia, M, Gong, P, Golshani, R, Wolfinger, R, Lababidi, S, Sahraeian, SMohammad E, Sherry, S, Han, T, Chen, T, Shi, T, Hou, W, Ge, W, Zou, W, Guo, W, Bao, W, Xiao, W, Fan, X, Gondo, Y, Yu, Y, Zhao, Y, Su, Z, Liu, Z, Tong, W, Xiao, W, Zook, JM, Zheng, Y, Hong, H|
|Date Published||2022 Jan 03|
|Keywords||Genome, Human, High-Throughput Nucleotide Sequencing, Humans, INDEL Mutation, Polymorphism, Single Nucleotide, Reproducibility of Results, Whole Genome Sequencing|
BACKGROUND: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS.
RESULTS: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×.
CONCLUSIONS: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.
|Alternate Journal||Genome Biol|
|PubMed Central ID||PMC8722114|
|Grant List||UM1 HG008898 / HG / NHGRI NIH HHS / United States|
Assessing reproducibility of inherited variants detected with short-read whole genome sequencing.
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