| Title: |
Assessing reproducibility of inherited variants detected with short-read whole genome sequencing |
| Authors: |
Pan, Bohu; Ren, Luyao; Onuchic, Vitor; Guan, Meijian; Kusko, Rebecca; Bruinsma, Steve; Trigg, Len; Scherer, Andreas; Ning, Baitang; Zhang, Chaoyang; Glidewell-Kenney, Christine; Xiao, Chunlin; Donaldson, Eric; Sedlazeck, Fritz J.; Schroth, Gary; Yavas, Gokhan; Grunenwald, Haiying; Chen, Haodong; Meinholz, Heather; Meehan, Joe; Wang, Jing; Yang, Jingcheng; Foox, Jonathan; Shang, Jun; Miclaus, Kelci; Dong, Lianhua; Shi, Leming; Mohiyuddin, Marghoob; Pirooznia, Mehdi; Gong, Ping; Golshani, Rooz; Wolfinger, Russ; Lababidi, Samir; Sahraeian, Sayed Mohammad Ebrahim; Sherry, Steve; Han, Tao; Chen, Tao; Shi, Tieliu; Hou, Wanwan; Ge, Weigong; Zou, Wen; Guo, Wenjing; Bao, Wenjun; Xiao, Wenzhong; Fan, Xiaohui; Gondo, Yoichi; Yu, Ying; Zhao, Yongmei; Su, Zhenqiang; Liu, Zhichao; Tong, Weida; Xiao, Wenming; Zook, Justin M.; Zheng, Yuanting; Hong, Huixiao |
| Contributors: |
Institute for Molecular Medicine Finland |
| Publisher Information: |
BioMed Central Ltd |
| Publication Year: |
2022 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
DATA SETS; GENOTYPE; MUTATION; CANCER; Medical biotechnology; 11832 Microbiology and virology; Genetics; developmental biology; physiology |
| Description: |
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 30x. 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. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Yuanting Zheng and Leming Shi were supported in part by the National Key R&D Project of China (2018YFE0201603, 2018YFE0201600, and 2017YFF0204600), the National Natural Science Foundation of China (31720103909 and 32170657), and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), State Key Laboratory of Genetic Engineering (SKLGE-2117), and the 111 Project (B13016). Chunlin Xiao and Steve Sherry were supported by the Intramural Research Program of the National Library of Medicine, National Institutes of Health. Yoichi Gondo was partly supported by JSPS KAKENHI no. 17H00789. Tieliu Shi was supported by the Open Research Fund of Key Laboratory of Advanced Theory and Application in Statistics and Data Science -MOE, ECNU and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01). Fritz J. Sedlazeck was supported by NIH (UM1 HG008898).; https://hdl.handle.net/10138/338968; 000737977500004 |
| Availability: |
https://hdl.handle.net/10138/338968 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.39389907 |
| Database: |
BASE |