DNA甲基化分析流程和软件集锦

 

DNA甲基化分析流程和软件集锦

DNA甲基化分析流程示意图

Workflow of high-throughput DNA methylation analysis. The workflow shows the basic process of high-throughput DNA methylation analysis by existing bioinformatics tools. The bioinformatics tools are shown in the ellipses and the corresponding functions in the neighboring boxs.

 

表1:基于二代测序检测DNA甲基化的方法(NGS-based technologies for detecting DNA methylation)

Pretreatment methodGenome coverageNGS-based analysisApplicationRef
Endonuclease digestionModerateMethl-seqAssay a range of genomic elements; allowing a broader survey of regions than classic methylation studies limited to CpG islands and promoters[16]
HELP-seqMeasurement of repetitive sequences, copy-number variability, allele-specific and smaller fragments (<50bp) ;Sensitivity of detection of hypomethylated loci[12,75]
MSCCIdentification of the unmethylated region of a genome by pinpointing unmethylated CpGs at single base-pair resolution[13,14]
Affinity enrichmentModerateMeDIP-seqGeneration of unbiased, cost-effective, and full-genome methylation levels without the limitations of restriction sites or CpG islands;[1,76]
MIRA-seqAnalyze recovered or double-stranded methylated DNA on a genome-wide scale; Applicable to various clinical and diagnostic situations.[19]
MDB-seqApplied to any biological settings to identify differentially methylated regions at the genomic scale[18]
MethylCap-seqDetection of differentially methylated regions with high genome coverage; Detect DMRs in clinical samples[20,77]
Bisulfite conversionHighBS-seqSensitively measure cytosine methylation on a genome-wide scale within specific sequence contexts[48,78]
RRBSAnalyze a limited number of gene promoters and regulatory sequence elements in a large number of samples; Analyzing and comparing genomic methylation patterns[11,28]
BSPPFocus sequencing on the most informative genomic regions ;exon capturing and SNP genotyping; Detecting methylation in large genomes[29]
BC-seqDetect site-specific switches in methylation; Determine DNA methylation frequencies in CGIs sampled from a variety of genomic settings including promoters, exons, introns, and intergenic loci[30]

 

表2:短Reads比对算法(Alignment tools for short reads.)

ResourcesURLRef
MAQhttp://maq.sourceforge.net/[33]
SOAPaligner/soap2http://soap.genomics.org.cn/index.html[36]
Bowtiehttp://bowtie-bio.sourceforge.net/index.shtml[32]
BLAThttp://genome.ucsc.edu/cgi-bin/hgBlat[79]
BWAhttp://maq.sourceforge.net/[80]
BFASThttp://bfast.sourceforge.net[81]
SHRiMPhttp://compbio.cs.toronto.edu/shrimp.[82]

 

备注:

  • SOAP, Short Oligonucleotide Analysis Package;
  • MAQ, Mapping and Assembly with Quality;
  • BLAT, BLAST-like alignment tool;
  • BWA, Burrows-Wheeler Alignment;
  • BFAST, BLAT-like Fast Accurate Search Tool;
  • SHRiMP, The Short-Read Mapping Package.

 

表3:检测峰值算法( Peak detection algorithms)

AlgorithmDescriptionAvailabilityRef
MACSModel-based analysis of ChIP-Seqhttp://liulab.dfci.harvard.edu/MACS/[41]
ChIPseeqerin-depth analysis of ChIP-seq datasetshttp://physiology.med.cornell.edu/faculty/elemento/lab/CS_files/ChIPseeqer-2.0.tar.gz[83]
HPeakA HMM-based algorithm for defining read enriched regionswww.sph.umich.edu/csg/qin/HPeak[84]
CASSysChIP-seq data Analysis Software Systemhttp://localness.zbh.uni-hamburg.de/~ProjektChipSeq/cgi-bin/login.rb[85]
PeakSeqA general scoring approach for ChIP-seq data analysis.http://info.gersteinlab.org/PeakSeq[86]
Sole-SearchIntegrated peak-calling and analysis softwarehttp://chipseq.genomecenter.ucdavis.edu/cgi-bin/chipseq.cgi[87]
SISSRSPrecise identification of binding sites from short reads generated from ChIP-Seq experimenthttp://sissrs.rajajothi.com/[88]
BayesPeakBayesian analysis of ChIP-seq datahttp://bioconductor.org/packages/release/bioc/html/BayesPeak.html[42]
PeakRangerA cloud-enabled peak caller for ChIP-seq datahttp://www.modencode.org/software/ranger/[89]
FindPeaks 3.1A tool for identifying areas of
enrichment
http://www.bcgsc.ca/platform/bioinfo/software/findpeaks[40]
Sole-SearchAn integrated analysis program for peak detection and functional annotation using ChIP-seq datahttp://chipseq.genomecenter.ucdavis.edu/cgi-bin/chipseq.cgi[87]
PeakAnalyzerGenome-wide annotation of chromatin binding and modification locihttp://www.bioinformatics.org/peakanalyzer/wiki/[90]
chromaSigA Probabilistic Approach to Finding Common Chromatin Signatureshttp://bioinformatics-renlab.ucsd.edu/rentrac/wiki/ChromaSig[43]
Fish the ChIPsA pipeline for automated genomic
annotation of ChIP-Seq data
http://bio.ifom-ieo-campus.it/ftc/[91]

 

 表4:分析亚硫酸盐测序测序数据的计算工具(Analysis of bisulfite sequencing data with computational tools)

ResourcesPurposeURLRef
RRBSMAPA fast, accurate and user-friendly alignment tool for reduced representation bisulfite sequencinghttp://rrbsmap.computational-epigenetics.org/[92]
BSMAPAhole genome bisulfite sequence mappinghttp://code.google.com/p/bsmap/[48]
BS SeekerPrecise mapping for bisulfite sequencinghttp://pellegrini.mcdb.ucla.edu/BS_Seeker/BS_Seeker.html[46]
BismarkMap and determine the Methylation state of BS-Seq readhttp://www.bioinformatics.bbsrc.ac.uk/projects/bismark/[47]
SOCS-BAn alignment algorithm for bisulfite sequencing using the Applied Biosystems SOLiD Systemhttp://solidsoftwaretools.com/gf/project/socs/[93]
BRATBisulfite-treated reads analysis toolhttp://compbio.cs.ucr.edu/brat/[94]
BISMAAnalysis of bisulfite Sequencing data from both unique and repetitive sequenceshttp://biochem.jacobs-university.de/BDPC/BISMA/[95]
BiQAnalyzerHTLocus-specific analysis of DNA methylation by high-throughput bisulfite sequencinghttp://biq-analyzer-ht.bioinf.mpi-inf.mpg.de/[49]
CpGviewerSequence analysis and editing for bisulphite genomic sequencing projectshttp://xserve1.leeds.ac.uk/~iancarr/cpgviewer[50]
CpG PatternFinderWindows-based program for bisulphite DNA-[52]
CyMATEBisulphite-based analysis of plant genomic DNAhttp://www.gmi.oeaw.ac.at/CyMATE[51]
GenomeStudio SoftwareAnalyzing data generated from Illumina assays--
MethMarkerDesign, optimize and validate DNA methylation biomarkers for a given DMRhttp://methmarker.mpi-inf.mpg.de/[96]
BDPCBisulfite sequencing Data methylation analysis.http://biochem.jacobs-university.de/BDPC[97]
MethylCoderSoftware pipeline for bisulte-treated sequenceshttps://github.com/brentp/methylcode[98]
QUMAQuantification tool for methylation analysishttp://quma.cdb.riken.jp/[53]

 

备注:

  • CyMATE ,Cytosine Methylation Analysis Tool for Everyone;
  • BSMAP, Bisulphite Sequence Mapping Program;
  • BISMA, Bisulfite Sequencing DNA Methylation Analysis;
  • BRAT,bisulte-treated reads analysis tool;
  • DMR, differentially methylated DNA region;
  • QUMA, Quantification Tool For Methylation Analysis.

 

表5:其他生物信息学软件(Bioinformatics tools)

ToolsPurposeUTRRef
MethDBDatabase for DNA methylation datahttp://www.methdb.de[54]
MethyCancer DatabaseDatabase of cancer DNA methylation datahttp://methycancer.psych.ac.cn/[57]
PubMethDatabase of DNA methylation literaturehttp://www.pubmeth.org/[99]
NGSmethDBDatabase for DNA methylation data at single-base resolutionhttp://bioinfo2.ugr.es/NGSmethDB/gbrowse/[55]
DBCATDatabase of CpG islands and analytical tools for identifying comprehensive methylation profiles in cancer cellshttp://dbcat.cgm.ntu.edu.tw/[100]
MethylomeDBDatabase of DNA methylation profiles of the brainhttp://epigenomics.columbia.edu/methylomedb/index.html[56]
DiseaseMethHuman disease methylation databasehttp://bioinfo.hrbmu.edu.cn/diseasemeth[58]
CpG IEIdentification of CpG islandshttp://bioinfo.hku.hk/cpgieintro.html[63]
CpG ISIdentification of CpG islandshttp://cpgislands.usc.edu/[64]
CG clustersIdentification of CpG islandshttp://greallylab.aecom.yu.edu/cgClusters/[68]
CpGclusterIdentification of CpG islandshttp://bioinfo2.ugr.es/CpGcluster[67]
CpGIFIdentification of CpG islandshttp://www.usd.edu/~sye/cpgisland/CpGIF.htm[101]
CpG_MIIdentification of CpG islandshttp://bioinfo.hrbmu.edu.cn/cpgmi[66]
CpGProDIdentification of CpG islandshttp://pbil.univ-lyon1.fr/software/cpgprod.html[65]
EpiGRAPHGenome scale statistical analysishttp://epigraph.mpi-inf.mpg.de/WebGRAPH[71]
GalaxyGeneral purpose analysishttp://main.g2.bx.psu.edu/[102]
QDMRIdentification of differentially methylated regionshttp://bioinfo.hrbmu.edu.cn/qdmr.[103]
BatmanMeDIP DNA methylation analysis toolhttp://td-blade.gurdon.cam.ac.uk/software/batman[23]
CisGenome BrowserA flexible tool for genomic data visualizationhttp://biogibbs.stanford.edu/~jiangh/browser/[70]
MethVisualVisualization and exploratory statistical analysis of DNA methylation profiles from bisulfite sequencinghttp://methvisual.molgen.mpg.de/[104]
MethToolsA toolbox to visualize and analyze DNA methylation datahttp://genome.imb-jena.de/methtools/[105]

 

以上内容摘选自:Su J, Huang D, Yan H, Liu H, Zhang Y (2012) Advances in Bioinformatics Tools for High-Throughput Sequencing Data of DNA Methylation. Hereditary Genet 1:107. doi: 10.4172/2161-1041.1000107。

各个软件后的参考文献请阅读论文原文查找。

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