Revealing Hi-C Subcompartments by Imputing Inter-chromosomal Chromatin Interactions

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Nov 9

PMID 31699985

Citations 64

Authors

Kyle Xiong

Jian Ma

Affiliations

Soon will be listed here.

Abstract

Higher-order genome organization and its variation in different cellular conditions remain poorly understood. Recent high-coverage genome-wide chromatin interaction mapping using Hi-C has revealed spatial segregation of chromosomes in the human genome into distinct subcompartments. However, subcompartment annotation, which requires Hi-C data with high sequencing coverage, is currently only available in the GM12878 cell line, making it impractical to compare subcompartment patterns across cell types. Here we develop a computational approach, SNIPER (Subcompartment iNference using Imputed Probabilistic ExpRessions), based on denoising autoencoder and multilayer perceptron classifier to infer subcompartments using typical Hi-C datasets with moderate coverage. SNIPER accurately reveals subcompartments using moderate coverage Hi-C datasets and outperforms an existing method that uses epigenomic features in GM12878. We apply SNIPER to eight additional cell lines and find that chromosomal regions with conserved and cell-type specific subcompartment annotations have different patterns of functional genomic features. SNIPER enables the identification of subcompartments without high-coverage Hi-C data and provides insights into the function and mechanisms of spatial genome organization variation across cell types.

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References

Zhang Y, An L, Xu J, Zhang B, Zheng W, Hu M . Enhancing Hi-C data resolution with deep convolutional neural network HiCPlus. Nat Commun. 2018; 9(1):750. PMC: 5821732. DOI: 10.1038/s41467-018-03113-2. View

Lieberman-Aiden E, van Berkum N, Williams L, Imakaev M, Ragoczy T, Telling A . Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009; 326(5950):289-93. PMC: 2858594. DOI: 10.1126/science.1181369. View

Rao S, Huang S, St Hilaire B, Engreitz J, Perez E, Kieffer-Kwon K . Cohesin Loss Eliminates All Loop Domains. Cell. 2017; 171(2):305-320.e24. PMC: 5846482. DOI: 10.1016/j.cell.2017.09.026. View

Quinodoz S, Ollikainen N, Tabak B, Palla A, Schmidt J, Detmar E . Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus. Cell. 2018; 174(3):744-757.e24. PMC: 6548320. DOI: 10.1016/j.cell.2018.05.024. View

Falk M, Feodorova Y, Naumova N, Imakaev M, Lajoie B, Leonhardt H . Heterochromatin drives compartmentalization of inverted and conventional nuclei. Nature. 2019; 570(7761):395-399. PMC: 7206897. DOI: 10.1038/s41586-019-1275-3. View

Libbrecht M, Ay F, Hoffman M, Gilbert D, Bilmes J, Noble W . Joint annotation of chromatin state and chromatin conformation reveals relationships among domain types and identifies domains of cell-type-specific expression. Genome Res. 2015; 25(4):544-57. PMC: 4381526. DOI: 10.1101/gr.184341.114. View

Bickmore W, van Steensel B . Genome architecture: domain organization of interphase chromosomes. Cell. 2013; 152(6):1270-84. DOI: 10.1016/j.cell.2013.02.001. View

Wang S, Su J, Beliveau B, Bintu B, Moffitt J, Wu C . Spatial organization of chromatin domains and compartments in single chromosomes. Science. 2016; 353(6299):598-602. PMC: 4991974. DOI: 10.1126/science.aaf8084. View

Kind J, Pagie L, de Vries S, Nahidiazar L, Dey S, Bienko M . Genome-wide maps of nuclear lamina interactions in single human cells. Cell. 2015; 163(1):134-47. PMC: 4583798. DOI: 10.1016/j.cell.2015.08.040. View

10.

Simonis M, Klous P, Splinter E, Moshkin Y, Willemsen R, de Wit E . Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C). Nat Genet. 2006; 38(11):1348-54. DOI: 10.1038/ng1896. View

11.

Hua N, Tjong H, Shin H, Gong K, Zhou X, Alber F . Producing genome structure populations with the dynamic and automated PGS software. Nat Protoc. 2018; 13(5):915-926. PMC: 6043163. DOI: 10.1038/nprot.2018.008. View

12.

Creyghton M, Cheng A, Welstead G, Kooistra T, Carey B, Steine E . Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A. 2010; 107(50):21931-6. PMC: 3003124. DOI: 10.1073/pnas.1016071107. View

13.

Grant C, Bailey T, Noble W . FIMO: scanning for occurrences of a given motif. Bioinformatics. 2011; 27(7):1017-8. PMC: 3065696. DOI: 10.1093/bioinformatics/btr064. View

14.

Tjong H, Li W, Kalhor R, Dai C, Hao S, Gong K . Population-based 3D genome structure analysis reveals driving forces in spatial genome organization. Proc Natl Acad Sci U S A. 2016; 113(12):E1663-72. PMC: 4812752. DOI: 10.1073/pnas.1512577113. View

15.

Rao S, Huntley M, Durand N, Stamenova E, Bochkov I, Robinson J . A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell. 2014; 159(7):1665-80. PMC: 5635824. DOI: 10.1016/j.cell.2014.11.021. View

16.

Durand N, Shamim M, Machol I, Rao S, Huntley M, Lander E . Juicer Provides a One-Click System for Analyzing Loop-Resolution Hi-C Experiments. Cell Syst. 2016; 3(1):95-8. PMC: 5846465. DOI: 10.1016/j.cels.2016.07.002. View

17.

Bonev B, Cavalli G . Organization and function of the 3D genome. Nat Rev Genet. 2016; 17(11):661-678. DOI: 10.1038/nrg.2016.112. View

18.

Beagrie R, Scialdone A, Schueler M, Kraemer D, Chotalia M, Xie S . Complex multi-enhancer contacts captured by genome architecture mapping. Nature. 2017; 543(7646):519-524. PMC: 5366070. DOI: 10.1038/nature21411. View

19.

Dai C, Li W, Tjong H, Hao S, Zhou Y, Li Q . Mining 3D genome structure populations identifies major factors governing the stability of regulatory communities. Nat Commun. 2016; 7:11549. PMC: 4895025. DOI: 10.1038/ncomms11549. View

20.

Khanna N, Hu Y, Belmont A . HSP70 transgene directed motion to nuclear speckles facilitates heat shock activation. Curr Biol. 2014; 24(10):1138-44. PMC: 4030642. DOI: 10.1016/j.cub.2014.03.053. View