Cargando…
Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2
HepG2 is one of the most widely used human cancer cell lines in biomedical research and one of the main cell lines of ENCODE. Although the functional genomic and epigenomic characteristics of HepG2 are extensively studied, its genome sequence has never been comprehensively analyzed and higher order...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486628/ https://www.ncbi.nlm.nih.gov/pubmed/30864654 http://dx.doi.org/10.1093/nar/gkz169 |
_version_ | 1783414376444723200 |
---|---|
author | Zhou, Bo Ho, Steve S Greer, Stephanie U Spies, Noah Bell, John M Zhang, Xianglong Zhu, Xiaowei Arthur, Joseph G Byeon, Seunggyu Pattni, Reenal Saha, Ishan Huang, Yiling Song, Giltae Perrin, Dimitri Wong, Wing H Ji, Hanlee P Abyzov, Alexej Urban, Alexander E |
author_facet | Zhou, Bo Ho, Steve S Greer, Stephanie U Spies, Noah Bell, John M Zhang, Xianglong Zhu, Xiaowei Arthur, Joseph G Byeon, Seunggyu Pattni, Reenal Saha, Ishan Huang, Yiling Song, Giltae Perrin, Dimitri Wong, Wing H Ji, Hanlee P Abyzov, Alexej Urban, Alexander E |
author_sort | Zhou, Bo |
collection | PubMed |
description | HepG2 is one of the most widely used human cancer cell lines in biomedical research and one of the main cell lines of ENCODE. Although the functional genomic and epigenomic characteristics of HepG2 are extensively studied, its genome sequence has never been comprehensively analyzed and higher order genomic structural features are largely unknown. The high degree of aneuploidy in HepG2 renders traditional genome variant analysis methods challenging and partially ineffective. Correct and complete interpretation of the extensive functional genomics data from HepG2 requires an understanding of the cell line’s genome sequence and genome structure. Using a variety of sequencing and analysis methods, we identified a wide spectrum of genome characteristics in HepG2: copy numbers of chromosomal segments at high resolution, SNVs and Indels (corrected for aneuploidy), regions with loss of heterozygosity, phased haplotypes extending to entire chromosome arms, retrotransposon insertions and structural variants (SVs) including complex and somatic genomic rearrangements. A large number of SVs were phased, sequence assembled and experimentally validated. We re-analyzed published HepG2 datasets for allele-specific expression and DNA methylation and assembled an allele-specific CRISPR/Cas9 targeting map. We demonstrate how deeper insights into genomic regulatory complexity are gained by adopting a genome-integrated framework. |
format | Online Article Text |
id | pubmed-6486628 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64866282019-05-01 Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2 Zhou, Bo Ho, Steve S Greer, Stephanie U Spies, Noah Bell, John M Zhang, Xianglong Zhu, Xiaowei Arthur, Joseph G Byeon, Seunggyu Pattni, Reenal Saha, Ishan Huang, Yiling Song, Giltae Perrin, Dimitri Wong, Wing H Ji, Hanlee P Abyzov, Alexej Urban, Alexander E Nucleic Acids Res Data Resources and Analyses HepG2 is one of the most widely used human cancer cell lines in biomedical research and one of the main cell lines of ENCODE. Although the functional genomic and epigenomic characteristics of HepG2 are extensively studied, its genome sequence has never been comprehensively analyzed and higher order genomic structural features are largely unknown. The high degree of aneuploidy in HepG2 renders traditional genome variant analysis methods challenging and partially ineffective. Correct and complete interpretation of the extensive functional genomics data from HepG2 requires an understanding of the cell line’s genome sequence and genome structure. Using a variety of sequencing and analysis methods, we identified a wide spectrum of genome characteristics in HepG2: copy numbers of chromosomal segments at high resolution, SNVs and Indels (corrected for aneuploidy), regions with loss of heterozygosity, phased haplotypes extending to entire chromosome arms, retrotransposon insertions and structural variants (SVs) including complex and somatic genomic rearrangements. A large number of SVs were phased, sequence assembled and experimentally validated. We re-analyzed published HepG2 datasets for allele-specific expression and DNA methylation and assembled an allele-specific CRISPR/Cas9 targeting map. We demonstrate how deeper insights into genomic regulatory complexity are gained by adopting a genome-integrated framework. Oxford University Press 2019-05-07 2019-03-13 /pmc/articles/PMC6486628/ /pubmed/30864654 http://dx.doi.org/10.1093/nar/gkz169 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Data Resources and Analyses Zhou, Bo Ho, Steve S Greer, Stephanie U Spies, Noah Bell, John M Zhang, Xianglong Zhu, Xiaowei Arthur, Joseph G Byeon, Seunggyu Pattni, Reenal Saha, Ishan Huang, Yiling Song, Giltae Perrin, Dimitri Wong, Wing H Ji, Hanlee P Abyzov, Alexej Urban, Alexander E Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2 |
title | Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2 |
title_full | Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2 |
title_fullStr | Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2 |
title_full_unstemmed | Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2 |
title_short | Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2 |
title_sort | haplotype-resolved and integrated genome analysis of the cancer cell line hepg2 |
topic | Data Resources and Analyses |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486628/ https://www.ncbi.nlm.nih.gov/pubmed/30864654 http://dx.doi.org/10.1093/nar/gkz169 |
work_keys_str_mv | AT zhoubo haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT hosteves haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT greerstephanieu haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT spiesnoah haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT belljohnm haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT zhangxianglong haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT zhuxiaowei haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT arthurjosephg haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT byeonseunggyu haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT pattnireenal haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT sahaishan haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT huangyiling haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT songgiltae haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT perrindimitri haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT wongwingh haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT jihanleep haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT abyzovalexej haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 AT urbanalexandere haplotyperesolvedandintegratedgenomeanalysisofthecancercelllinehepg2 |