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Assessing reproducibility of inherited variants detected with short-read 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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722114/ https://www.ncbi.nlm.nih.gov/pubmed/34980216 http://dx.doi.org/10.1186/s13059-021-02569-8 |
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author | 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 |
author_facet | 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 |
author_sort | Pan, Bohu |
collection | PubMed |
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 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-021-02569-8. |
format | Online Article Text |
id | pubmed-8722114 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-87221142022-01-06 Assessing reproducibility of inherited variants detected with short-read whole genome sequencing 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 Genome Biol Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-021-02569-8. BioMed Central 2022-01-03 /pmc/articles/PMC8722114/ /pubmed/34980216 http://dx.doi.org/10.1186/s13059-021-02569-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research 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 Assessing reproducibility of inherited variants detected with short-read whole genome sequencing |
title | Assessing reproducibility of inherited variants detected with short-read whole genome sequencing |
title_full | Assessing reproducibility of inherited variants detected with short-read whole genome sequencing |
title_fullStr | Assessing reproducibility of inherited variants detected with short-read whole genome sequencing |
title_full_unstemmed | Assessing reproducibility of inherited variants detected with short-read whole genome sequencing |
title_short | Assessing reproducibility of inherited variants detected with short-read whole genome sequencing |
title_sort | assessing reproducibility of inherited variants detected with short-read whole genome sequencing |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722114/ https://www.ncbi.nlm.nih.gov/pubmed/34980216 http://dx.doi.org/10.1186/s13059-021-02569-8 |
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