RT Journal Article
SR Electronic
T1 Measuring the reproducibility and quality of Hi-C data
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 188755
DO 10.1101/188755
A1 Galip Gürkan Yardimci
A1 Hakan Ozadam
A1 Michael E.G. Sauria
A1 Oana Ursu
A1 Koon-Kiu Yan
A1 Tao Yang
A1 Abhijit Chakraborty
A1 Arya Kaul
A1 Bryan R. Lajoie
A1 Fan Song
A1 Ye Zhang
A1 Ferhat Ay
A1 Mark Gerstein
A1 Anshul Kundaje
A1 Qunhua Li
A1 James Taylor
A1 Feng Yue
A1 Job Dekker
A1 William S. Noble
YR 2017
UL http://biorxiv.org/content/early/2017/09/14/188755.abstract
AB 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/kundaje/3DChromatin_ReplicateQC to facilitate adoption in the community.