TY - JOUR
T1 - Analysis of Hi-C data using SIP effectively identifies loops in organisms from C. Elegans to mammals
AU - Jordan Rowley, M.
AU - Poulet, Axel
AU - Nichols, Michael H.
AU - Bixler, Brianna J.
AU - Sanborn, Adrian L.
AU - Brouhard, Elizabeth A.
AU - Hermetz, Karen
AU - Linsenbaum, Hannah
AU - Csankovszki, Gyorgyi
AU - Aiden, Erez Lieberman
AU - Corces, Victor G.
N1 - Funding Information:
We thank the HudsonAlpha Institute for Biotechnology Genomic Services Lab for their help in Illumina Sequencing. We also thank Drs. William Noble and Doug Phanstiel for constructive discussions during the optimization of SIP. This work was supported by National Institutes of Health (NIH) Pathway to Independence Award K99/R00 GM127671 (M.J.R.) and U.S. Public Health Service Award R01 GM035463 (V.G.C.) from the National Institutes of Health. B.J.B. was supported by NIH T32 GM008490. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 Rowley et al.; Published by Cold Spring Harbor Laboratory Press.
PY - 2020
Y1 - 2020
N2 - Chromatin loops are a major component of 3D nuclear organization, visually apparent as intense point-to-point interactions in Hi-C maps. Identification of these loops is a critical part of most Hi-C analyses. However, current methods often miss visually evident CTCF loops in Hi-C data sets from mammals, and they completely fail to identify high intensity loops in other organisms. We present SIP, Significant Interaction Peak caller, and SIPMeta, which are platform independent programs to identify and characterize these loops in a time- and memory-efficient manner. We show that SIP is resistant to noise and sequencing depth, and can be used to detect loops that were previously missed in human cells as well as loops in other organisms. SIPMeta corrects for a common visualization artifact by accounting for Manhattan distance to create average plots of Hi-C and HiChIP data. We then demonstrate that the use of SIP and SIPMeta can lead to biological insights by characterizing the contribution of several transcription factors to CTCF loop stability in human cells. We also annotate loops associated with the SMC component of the dosage compensation complex (DCC) in Caenorhabditis elegans and demonstrate that loop anchors represent bidirectional blocks for symmetrical loop extrusion. This is in contrast to the asymmetrical extrusion until unidirectional blockage by CTCF that is presumed to occur in mammals. Using HiChIP and multiway ligation events, we then show that DCC loops form a network of strong interactions that may contribute to X Chromosome-wide condensation in C. elegans hermaphrodites.
AB - Chromatin loops are a major component of 3D nuclear organization, visually apparent as intense point-to-point interactions in Hi-C maps. Identification of these loops is a critical part of most Hi-C analyses. However, current methods often miss visually evident CTCF loops in Hi-C data sets from mammals, and they completely fail to identify high intensity loops in other organisms. We present SIP, Significant Interaction Peak caller, and SIPMeta, which are platform independent programs to identify and characterize these loops in a time- and memory-efficient manner. We show that SIP is resistant to noise and sequencing depth, and can be used to detect loops that were previously missed in human cells as well as loops in other organisms. SIPMeta corrects for a common visualization artifact by accounting for Manhattan distance to create average plots of Hi-C and HiChIP data. We then demonstrate that the use of SIP and SIPMeta can lead to biological insights by characterizing the contribution of several transcription factors to CTCF loop stability in human cells. We also annotate loops associated with the SMC component of the dosage compensation complex (DCC) in Caenorhabditis elegans and demonstrate that loop anchors represent bidirectional blocks for symmetrical loop extrusion. This is in contrast to the asymmetrical extrusion until unidirectional blockage by CTCF that is presumed to occur in mammals. Using HiChIP and multiway ligation events, we then show that DCC loops form a network of strong interactions that may contribute to X Chromosome-wide condensation in C. elegans hermaphrodites.
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U2 - 10.1101/gr.257832.119
DO - 10.1101/gr.257832.119
M3 - Article
C2 - 32127418
AN - SCOPUS:85082523177
SN - 1088-9051
VL - 30
SP - 447
EP - 458
JO - Genome Research
JF - Genome Research
IS - 3
ER -