Home LiteratureArticle Details
PMID: 20852634 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Quantitative comparison of genome-wide DNA methylation mapping technologies.

Nature biotechnology ·Vol. 28 ·No. 10 ·2010-10-00 ·Pages 1106-14

Bock C, Tomazou EM, Brinkman AB, Müller F, Simmer F, Gu H, Jäger N, Gnirke A, Stunnenberg HG, Meissner A

Abstract

DNA methylation plays a key role in regulating eukaryotic gene expression. Although mitotically heritable and stable over time, patterns of DNA methylation frequently change in response to cell differentiation, disease and environmental influences. Several methods have been developed to map DNA methylation on a genomic scale. Here, we benchmark four of these approaches by analyzing two human embryonic stem cell lines derived from genetically unrelated embryos and a matched pair of colon tumor and adjacent normal colon tissue obtained from the same donor. Our analysis reveals that methylated DNA immunoprecipitation sequencing (MeDIP-seq), methylated DNA capture by affinity purification (MethylCap-seq), reduced representation bisulfite sequencing (RRBS) and the Infinium HumanMethylation27 assay all produce accurate DNA methylation data. However, these methods differ in their ability to detect differentially methylated regions between pairs of samples. We highlight strengths and weaknesses of the four methods and give practical recommendations for the design of epigenomic case-control studies.

MeSH Terms
Aged, 80 and over Cell Line DNA Methylation/genetics Genome, Human/genetics Humans Male Repetitive Sequences, Nucleic Acid/genetics Reproducibility of Results Sequence Analysis, DNA/methods
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Bock Christoph
Broad Institute, Cambridge, Massachusetts, USA. [email protected]
Tomazou Eleni M
Brinkman Arie B
Müller Fabian
Simmer Femke
Gu Hongcang
Jäger Natalie
Gnirke Andreas
Stunnenberg Hendrik G
Meissner Alexander
References (64)
64 references, click to expand
  1. Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping.
    Nucleic Acids Res. 2008 Jun;36(10):e55 PMID: 18413340
  2. The epigenome: archive of the prenatal environment.
    Epigenetics. 2009 Nov 16;4(8):526-31 PMID: 19923908
  3. DNA methylation biomarkers for blood-based colorectal cancer screening.
    Clin Chem. 2008 Feb;54(2):414-23 PMID: 18089654
  4. The landscape of somatic copy-number alteration across human cancers.
    Nature. 2010 Feb 18;463(7283):899-905 PMID: 20164920
  5. Methylated-CpG island recovery assay: a new technique for the rapid detection of methylated-CpG islands in cancer.
    Lab Invest. 2005 Sep;85(9):1172-80 PMID: 16025148
  6. Histone modifications at human enhancers reflect global cell-type-specific gene expression.
    Nature. 2009 May 7;459(7243):108-12 PMID: 19295514
  7. A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis.
    Nat Biotechnol. 2008 Jul;26(7):779-85 PMID: 18612301
  8. CpG island methylator phenotype in cancer.
    Nat Rev Cancer. 2004 Dec;4(12):988-93 PMID: 15573120
  9. Epigenetic biomarker development.
    Epigenomics. 2009 Oct;1(1):99-110 PMID: 22122639
  10. Cytosine methylation and the ecology of intragenomic parasites.
    Trends Genet. 1997 Aug;13(8):335-40 PMID: 9260521
  11. Comprehensive high-throughput arrays for relative methylation (CHARM).
    Genome Res. 2008 May;18(5):780-90 PMID: 18316654
  12. Genome-wide DNA methylation profiling using Infinium® assay.
    Epigenomics. 2009 Oct;1(1):177-200 PMID: 22122642
  13. Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction?
    Nat Rev Cancer. 2006 Feb;6(2):107-16 PMID: 16491070
  14. MethPrimer: designing primers for methylation PCRs.
    Bioinformatics. 2002 Nov;18(11):1427-31 PMID: 12424112
  15. Wnt antagonist gene DKK2 is epigenetically silenced and inhibits renal cancer progression through apoptotic and cell cycle pathways.
    Clin Cancer Res. 2009 Sep 15;15(18):5678-87 PMID: 19755393
  16. Excessive CpG island hypermethylation in cancer cell lines versus primary human malignancies.
    Hum Mol Genet. 2001 Jun 15;10(13):1413-9 PMID: 11440994
  17. NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins.
    Nucleic Acids Res. 2007 Jan;35(Database issue):D61-5 PMID: 17130148
  18. Cancer epigenetics comes of age.
    Nat Genet. 1999 Feb;21(2):163-7 PMID: 9988266
  19. Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency.
    Nature. 2010 Feb 25;463(7284):1101-5 PMID: 20098412
  20. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells.
    Nat Genet. 2005 Aug;37(8):853-62 PMID: 16007088
  21. Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution.
    Nat Methods. 2010 Feb;7(2):133-6 PMID: 20062050
  22. Whole-genome DNA methylation profiling using MethylCap-seq.
    Methods. 2010 Nov;52(3):232-6 PMID: 20542119
  23. GATA4 and GATA5 are potential tumor suppressors and biomarkers in colorectal cancer.
    Clin Cancer Res. 2009 Jun 15;15(12):3990-7 PMID: 19509152
  24. The history of cancer epigenetics.
    Nat Rev Cancer. 2004 Feb;4(2):143-53 PMID: 14732866
  25. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores.
    Nat Genet. 2009 Feb;41(2):178-186 PMID: 19151715
  26. Epigenetic inactivation of the canonical Wnt antagonist SRY-box containing gene 17 in colorectal cancer.
    Cancer Res. 2008 Apr 15;68(8):2764-72 PMID: 18413743
  27. Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies.
    Lancet Neurol. 2009 Nov;8(11):1056-72 PMID: 19833297
  28. ChIP-seq: advantages and challenges of a maturing technology.
    Nat Rev Genet. 2009 Oct;10(10):669-80 PMID: 19736561
  29. Genome-scale DNA methylation maps of pluripotent and differentiated cells.
    Nature. 2008 Aug 7;454(7205):766-70 PMID: 18600261
  30. The Wnt antagonist sFRP1 in colorectal tumorigenesis.
    Cancer Res. 2004 Feb 1;64(3):883-8 PMID: 14871816
  31. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific.
    Hum Mol Genet. 2009 Nov 1;18(21):4046-53 PMID: 19656776
  32. Epigenetics in cancer.
    N Engl J Med. 2008 Mar 13;358(11):1148-59 PMID: 18337604
  33. DNA-methylation analysis by the bisulfite-assisted genomic sequencing method.
    Methods Mol Biol. 2002;200:143-54 PMID: 11951649
  34. Analysis of repetitive element DNA methylation by MethyLight.
    Nucleic Acids Res. 2005 Dec 02;33(21):6823-36 PMID: 16326863
  35. CpG island mapping by epigenome prediction.
    PLoS Comput Biol. 2007 Jun;3(6):e110 PMID: 17559301
  36. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts.
    Nat Genet. 2009 Dec;41(12):1350-3 PMID: 19881528
  37. The epigenomics of cancer.
    Cell. 2007 Feb 23;128(4):683-92 PMID: 17320506
  38. Global analysis of DNA methylation and transcription of human repetitive sequences.
    Epigenetics. 2009 Jul 1;4(5):339-50 PMID: 19633427
  39. DNA hypomethylation in cancer cells.
    Epigenomics. 2009 Dec;1(2):239-59 PMID: 20495664
  40. Human DNA methylomes at base resolution show widespread epigenomic differences.
    Nature. 2009 Nov 19;462(7271):315-22 PMID: 19829295
  41. Primer: epigenetics of autoimmunity.
    Nat Clin Pract Rheumatol. 2007 Sep;3(9):521-7 PMID: 17762851
  42. Repbase update: a database and an electronic journal of repetitive elements.
    Trends Genet. 2000 Sep;16(9):418-20 PMID: 10973072
  43. Mapping short DNA sequencing reads and calling variants using mapping quality scores.
    Genome Res. 2008 Nov;18(11):1851-8 PMID: 18714091
  44. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences.
    Behav Res Methods. 2007 May;39(2):175-91 PMID: 17695343
  45. Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis.
    Nucleic Acids Res. 2005 Oct 13;33(18):5868-77 PMID: 16224102
  46. MBD-isolated Genome Sequencing provides a high-throughput and comprehensive survey of DNA methylation in the human genome.
    Nucleic Acids Res. 2010 Jan;38(2):391-9 PMID: 19906696
  47. Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21.
    Nat Genet. 2008 May;40(5):631-7 PMID: 18372901
  48. Computational epigenetics.
    Bioinformatics. 2008 Jan 1;24(1):1-10 PMID: 18024971
  49. High-throughput bisulfite sequencing in mammalian genomes.
    Methods. 2009 Jul;48(3):226-32 PMID: 19442738
  50. An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs).
    Genome Res. 2008 Sep;18(9):1518-29 PMID: 18577705
  51. Derivation of embryonic stem-cell lines from human blastocysts.
    N Engl J Med. 2004 Mar 25;350(13):1353-6 PMID: 14999088
  52. Statistical significance for genomewide studies.
    Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5 PMID: 12883005
  53. Phenotypic plasticity and the epigenetics of human disease.
    Nature. 2007 May 24;447(7143):433-40 PMID: 17522677
  54. Finding the missing heritability of complex diseases.
    Nature. 2009 Oct 8;461(7265):747-53 PMID: 19812666
  55. Prospects for epigenetic epidemiology.
    Am J Epidemiol. 2009 Feb 15;169(4):389-400 PMID: 19139055
  56. Cancer epigenomics: DNA methylomes and histone-modification maps.
    Nat Rev Genet. 2007 Apr;8(4):286-98 PMID: 17339880
  57. DNA methylation profiling of human chromosomes 6, 20 and 22.
    Nat Genet. 2006 Dec;38(12):1378-85 PMID: 17072317
  58. Creation of genomic methylation patterns.
    Nat Genet. 1996 Apr;12(4):363-7 PMID: 8630488
  59. Genome-wide tracking of unmethylated DNA Alu repeats in normal and cancer cells.
    Nucleic Acids Res. 2008 Feb;36(3):770-84 PMID: 18084025
  60. BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing.
    Bioinformatics. 2005 Nov 1;21(21):4067-8 PMID: 16141249
  61. Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver.
    Genome Res. 2009 Jun;19(6):1044-56 PMID: 19273619
  62. Global variation in copy number in the human genome.
    Nature. 2006 Nov 23;444(7118):444-54 PMID: 17122850
  63. MEDME: an experimental and analytical methodology for the estimation of DNA methylation levels based on microarray derived MeDIP-enrichment.
    Genome Res. 2008 Oct;18(10):1652-9 PMID: 18765822
  64. High-resolution genome-wide cytosine methylation profiling with simultaneous copy number analysis and optimization for limited cell numbers.
    Nucleic Acids Res. 2009 Jul;37(12):3829-39 PMID: 19386619
Article Info
Journal
Nature biotechnology
Abbr.
Nat Biotechnol
ISSN
1546-1696
Published
2010-10-00
Epub
2010-00-19
Pages
1106-14
Language
English
Region
United States
NLM ID
9604648
PMCID
PMC3066564
Subset
IM
Grants
NIEHS NIH HHS · U01 ES017155 · United States
NIEHS NIH HHS · U01 ES017155-04 · United States
NIEHS NIH HHS · U01ES017155 · United States
Corrections
CommentIn
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]