Hi-C技术主要将空间结构临近的DNA片段进行交联,并将交联的DNA片段富集,然后进行高通量测序,对测序数据进行分析即可揭示全基因组范围内的染色体片段间的交互作用。利用Hi-C技术可以揭示基因组的一般结构特征,包括从隔室(动物中A/BCompartments,植物中为CSD/LSD)到拓扑相关结构域(动物中TAD,植物中TAD-like),最后再到环(loop)的染色质的这种层级结构.
染色体的三维(3D)结构深刻影响DNA复制,转录及DNA损伤修复。最近研究揭示了人基因组中存在数百万的潜在的顺式调控元件,其中大量位于基因间区和远离其靶基因的启动子区。这些主要由增强子组成的远端调控元件,在生物发育过程中通过基因组中形成的Loop结构影响目标基因的转录,从而实现对目标基因的调控.
另外通过结合BS-seq、ChIP-seq和RNA-seq数据分析发现揭示染色体空间结构与基因组表观遗传修饰和转录活性关系,共同来阐释核基因组的包装模式。
说了这么多,下面小编就罗列一下目前做HI-C常用的工具:
一.数据标准化
1.HiCNorm
http://www.people.fas.harvard.edu/~junliu/HiCNorm/
2. ICE
https://mirnylab.bitbucket.io/hiclib/index.html
3.HiC-Pro
https://github.com/nservant/HiC-Pro
二. TAD鉴定
1. HiCseg:Modelsthe uncertainty in Hi‐C data
https://cran.r-project.org/web/packages/HiCseg/index.html
2. TADbit
https://github.com/3DGenomes/TADbit
3. DomainCaller
http://chromosome.sdsc.edu/mouse/hi-c/download.html
4. InsulationScore:Robustto different sequencing depth;
can detectdynamics of TAD boundaries
https://github.com/dekkerlab/crane-nature-2015
5. Arrowhead:Highcomputational efficiency with
dynamicprogramming
https://github.com/theaidenlab/juicer/wiki/Download
6. TADtree
compbio.cs.brown.edu/projects/tadtree/
7. Armatus:TADcalling robust in different resolutions
https://github.com/kingsfordgroup/armatus
8. Topdom
http://zhoulab.usc.edu/TopDom/
三.交互片段鉴定(interaction)
1. Fit-Hi-C:Accuratebackground model using
non-parametricspline
http://noble.gs.washington.edu/proj/fit-hi-c
2. GOTHiC :Modelscontact-frequency uncertainty
as binomialdistribution
http://bioconductor.org/packages/release/bioc/html/GOTHiC.html
3. HOMER
homer.ucsd.edu/homer/download.html
4. HIPPIE
wanglab.pcbi.upenn.edu/hippie
5. diffHic
https://bioconductor.org/packages/release/bioc/html/diffHic.html
6. HiCCUPS:Designedfor high-resolution Hi‐C data
https://github.com/theaidenlab/juicer/wiki/Download
四.3D构象:
1. 3D-GNOME
https://bitbucket.org/3dome/3dome_mmc
2.Tadbit
https://github.com/3DGenomes/tadbit
五.可视化:
1.HiCPlotter
https://github.com/kcakdemir/HiCPlotter