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1 技術(shù)簡介
Hi-C技術(shù)以整個(gè)細(xì)胞核為研究對象,利用高通量測序技術(shù),結(jié)合生物信息學(xué)方法,研究全基因組范圍內(nèi)整個(gè)染色質(zhì)DNA在空間位置上的關(guān)系;通過對染色質(zhì)內(nèi)全部DNA相互作用模式進(jìn)行捕獲,獲得高分辨率的染色質(zhì)三維結(jié)構(gòu)信息,并與ChIP-seq、轉(zhuǎn)錄組數(shù)據(jù)聯(lián)合分析,從基因調(diào)控網(wǎng)絡(luò)和表觀遺傳網(wǎng)絡(luò)來闡述生物體性狀形成的相關(guān)機(jī)制。
2 實(shí)驗(yàn)流程
3 分析流程
4 主要結(jié)果
4.1 測序質(zhì)量評估
4.2 迭代比對及過濾
4.3 互作矩陣構(gòu)建及校正
4.4 TAD 結(jié)構(gòu)分析
4.5 顯著互作位點(diǎn)分析
4.6 樣本間顯著互作的比較
染色體結(jié)構(gòu)三維建模
兩樣本差異矩陣全局互作熱圖
兩樣本TADs?Insulator差異圖
差異矩陣與多組學(xué)聯(lián)合展示圖
5 參考文獻(xiàn)
1. Lieberman-Aiden E, Van Berkum N L, Williams L, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome[J]. Science, 2009, 326(5950): 289-293.
2. Kalhor R, Tjong H, Jayathilaka N, et al. Genome architectures revealed by tethered chromosome conformation capture and population-based modeling[J]. Nature biotechnology, 2012, 30(1): 90-98.
3. Rao S S P, Huntley M H, Durand N C, et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping[J]. Cell, 2014, 159(7): 1665-1680.
4. Nagano T, Várnai C, Schoenfelder S, et al. Comparison of Hi-C results using in-solution versus in-nucleus ligation[J]. Genome biology, 2015, 16(1): 175.
5. Liang Z, Li G, Wang Z, et al. BL-Hi-C is an efficient and sensitive approach for capturing structural and regulatory chromatin interactions[J]. Nature Communications, 2017, 8(1): 1622.