TY - JOUR T1 - Measuring the reproducibility and quality of Hi-C data JF - bioRxiv DO - 10.1101/188755 SP - 188755 AU - Galip Gürkan Yardımcı AU - Hakan Ozadam AU - Michael E.G. Sauria AU - Oana Ursu AU - Koon-Kiu Yan AU - Tao Yang AU - Abhijit Chakraborty AU - Arya Kaul AU - Bryan R. Lajoie AU - Fan Song AU - Ye Zhang AU - Ferhat Ay AU - Mark Gerstein AU - Anshul Kundaje AU - Qunhua Li AU - James Taylor AU - Feng Yue AU - Job Dekker AU - William S. Noble Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/02/05/188755.abstract N2 - 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. 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 (e.g., ratio of intra to interchromosomal interactions) and novel (e.g., QuASAR-QC) measures to identify low quality experiments. 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. ER -