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Measuring the reproducibility and quality of Hi-C data
- Yardımcı, Galip Gürkan, Ozadam, Hakan, Sauria, Michael E. G., Ursu, Oana, Yan, Koon-Kiu, Yang, Tao, Chakraborty, Abhijit, Kaul, Arya, Lajoie, Bryan R., Song, Fan, Zhan, Ye, Ay, Ferhat, Gerstein, Mark, Kundaje, Anshul, Li, Qunhua, Taylor, James, Yue, Feng, Dekker, Job, Noble, William S.
- Genome biology 2019 v.20 no.1 pp. 57
- DNA replication, cell lines, computer analysis, computer software, gene expression regulation, genes
- BACKGROUND: Hi-C is currently the most widely used assay to investigate the 3D organization of the genome and to study its role in gene regulation, DNA replication, and disease. However, Hi-C experiments are costly to perform and involve multiple complex experimental steps; thus, accurate methods for measuring the quality and reproducibility of Hi-C data are essential to determine whether the output should be used further in a study. RESULTS: Using real and simulated data, we profile the performance of several recently proposed methods for assessing reproducibility of population Hi-C data, including HiCRep, GenomeDISCO, HiC-Spector, and QuASAR-Rep. By explicitly controlling noise and sparsity through simulations, we demonstrate the deficiencies of performing simple correlation analysis on pairs of matrices, and we show that methods developed specifically for Hi-C data produce better measures of reproducibility. We also show how to use established measures, such as the ratio of intra- to interchromosomal interactions, and novel ones, such as QuASAR-QC, to identify low-quality experiments. CONCLUSIONS: In this work, we assess reproducibility and quality measures by varying sequencing depth, resolution and noise levels in Hi-C data from 13 cell lines, with two biological replicates each, as well as 176 simulated matrices. Through this extensive validation and benchmarking of Hi-C data, we describe best practices for reproducibility and quality assessment of Hi-C experiments. We make all software publicly available at http://github.com/kundajelab/3DChromatin_ReplicateQC to facilitate adoption in the community.