Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA

Nature Genetics
Shicheng GuoKun Zhang

Abstract

Adjacent CpG sites in mammalian genomes can be co-methylated owing to the processivity of methyltransferases or demethylases, yet discordant methylation patterns have also been observed, which are related to stochastic or uncoordinated molecular processes. We focused on a systematic search and investigation of regions in the full human genome that show highly coordinated methylation. We defined 147,888 blocks of tightly coupled CpG sites, called methylation haplotype blocks, after analysis of 61 whole-genome bisulfite sequencing data sets and validation with 101 reduced-representation bisulfite sequencing data sets and 637 methylation array data sets. Using a metric called methylation haplotype load, we performed tissue-specific methylation analysis at the block level. Subsets of informative blocks were further identified for deconvolution of heterogeneous samples. Finally, using methylation haplotypes we demonstrated quantitative estimation of tumor load and tissue-of-origin mapping in the circulating cell-free DNA of 59 patients with lung or colorectal cancer.

References

Apr 1, 1981·Cell·M WiglerM Perucho
Mar 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Daiya Takai, Peter A Jones
Apr 25, 2006·Biostatistics·W Evan JohnsonAriel Rabinovic
Feb 1, 2011·Nucleic Acids Research·Hehuang XieMarcelo B Soares
Apr 15, 2011·Nature·Kristine WilliamsKristian Helin
Jun 28, 2011·Nature Genetics·Kasper Daniel HansenAndrew P Feinberg
Mar 20, 2012·Cell·Elisabet Pujadas, Andrew P Feinberg
May 10, 2012·BMC Bioinformatics·E Andres HousemanKarl T Kelsey
Jun 13, 2012·Proceedings of the National Academy of Sciences of the United States of America·Holger HeynManel Esteller
Sep 8, 2012·Nature·ENCODE Project Consortium
Sep 8, 2012·Nature·Robert E ThurmanJohn A Stamatoyannopoulos
Aug 9, 2013·Nature·Michael J ZillerAlexander Meissner
Oct 15, 2013·Cell·Denes HniszRichard A Young
Mar 29, 2014·Nature·Robin AnderssonAlbin Sandelin
Jul 30, 2014·Nature Reviews. Genetics·Bryony Jones
Aug 6, 2014·Nature Reviews. Genetics·Esther Lau
Feb 20, 2015·Nature·Roadmap Epigenomics ConsortiumManolis Kellis
Jun 2, 2015·Nature·Matthew D SchultzJoseph R Ecker
Sep 9, 2015·Genome Biology·James A TimmonsIain J Gallagher
Sep 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Kun SunYuk Ming Dennis Lo
Oct 16, 2015·Nature Reviews. Genetics·Omer Schwartzman, Amos Tanay
Nov 18, 2015·Epigenetics : Official Journal of the DNA Methylation Society·Daisuke Saito, Mikita Suyama
Mar 16, 2016·Proceedings of the National Academy of Sciences of the United States of America·Roni Lehmann-WermanYuval Dor
Jul 1, 2016·BMC Bioinformatics·E Andres HousemanCarmen J Marsit

Citations

May 5, 2017·International Journal of Cancer. Journal International Du Cancer·Peter UlzMichael R Speicher
Jul 5, 2017·Nature Reviews. Clinical Oncology·Sebastián MoranManel Esteller
Jan 31, 2018·The Journal of Pathology·Caitlin M StewartDana Wy Tsui
Feb 14, 2018·Epigenetics : Official Journal of the DNA Methylation Society·Olga VeraInmaculada Ibanez de Caceres
Sep 14, 2017·BMC Genomics·Camila M Lopes-RamosKimberly Glass
Oct 29, 2018·Annals of Hematology·Fang-Tian WuJian-Yong Li
Jan 27, 2019·Genes·Julia Romanowska, Anagha Joshi
Feb 15, 2019·Expert Review of Molecular Diagnostics·Vivian Weiwen XueWilliam Chi Shing Cho
Feb 13, 2019·International Journal of Cancer. Journal International Du Cancer·Jian WuJinke Wang
Mar 27, 2019·Journal of Cellular and Molecular Medicine·Pingting GaoPinghong Zhou
Nov 14, 2017·Nature Reviews. Genetics·Andrew E Teschendorff, Caroline L Relton
Jun 20, 2019·Cancers·Chiang-Ching HuangLiang Wang
Aug 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Alexandre Pellan ChengIwijn De Vlaminck
Feb 10, 2019·Clinical Chemistry·Huichuan YuYanxin Luo
Feb 28, 2020·Nucleic Acids Research·Michael SchererMarkus List
Mar 11, 2020·PLoS Neglected Tropical Diseases·Zhengqing WanZhuohua Zhang
Apr 28, 2020·Journal of Cancer Research and Clinical Oncology·Sameer A Dhayat, Zixuan Yang
May 13, 2020·Critical Reviews in Clinical Laboratory Sciences·Vida UngererStefan Holdenrieder
Dec 4, 2019·Nature Communications·Harry MacKayRobert A Waterland
Sep 20, 2017·The Cancer Journal·Rachael J WernerJean-Pierre J Issa
Jul 15, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Ruben Van PaemelBram De Wilde
Jul 29, 2018·Nature Genetics·Dinh Diep, Kun Zhang
Nov 28, 2018·Nature Materials·Andrew E Teschendorff
Dec 24, 2019·Critical Reviews in Clinical Laboratory Sciences·Abel Jacobus BronkhorstStefan Holdenrieder
Jul 23, 2020·Journal of Oncology·Rilan BaiJiuwei Cui
Nov 9, 2017·Cellular and Molecular Life Sciences : CMLS·Lesca M HoldtDaniel Teupser
Oct 25, 2017·Journal of Hematology & Oncology·Yi-Chen ZhangYi-Long Wu
Aug 1, 2018·Frontiers in Oncology·Kentaro SawadaHideaki Bando
Apr 20, 2018·Briefings in Bioinformatics·Hao FengHao Wu
Nov 10, 2018·Nature Reviews. Genetics·Ellen HeitzerMichael R Speicher
Apr 20, 2019·BMC Bioinformatics·Andrea TangherloniDaniela Besozzi
Jun 7, 2018·NPJ Precision Oncology·Ellen HeitzerMichael R Speicher
Dec 28, 2019·Genes·Mariarita BrancaccioTiziana Angrisano
Dec 23, 2018·Aging Cell·Yee Voan TeoNicola Neretti
Jul 24, 2019·Nucleic Acids Research·Mengchi WangWei Wang
Apr 8, 2020·BioMed Research International·Yuhan DingLei Ding
Oct 17, 2017·Annual Review of Pharmacology and Toxicology·Volker M LauschkeMagnus Ingelman-Sundberg
Sep 25, 2020·Cancer Science·DaPeng LiBinBin Cui
Oct 20, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Ruben Van PaemelKatleen De Preter
Dec 15, 2020·Briefings in Bioinformatics·Yue YinDeqiang Sun
Dec 19, 2020·Biomolecules·Francesca GalardiMatteo Benelli
Sep 29, 2018·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Wensheng ZhangKun Zhang
Aug 21, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thomas R PisanicIe-Ming Shih
Jan 5, 2021·The Journal of Clinical Endocrinology and Metabolism·Hui ZhangZhiyong Liang

Related Concepts

Genome Mapping
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