MIA-Sig: multiplex chromatin interaction analysis by signal processing and statistical algorithms

Abstract

The single-molecule multiplex chromatin interaction data are generated by emerging 3D genome mapping technologies such as GAM, SPRITE, and ChIA-Drop. These datasets provide insights into high-dimensional chromatin organization, yet introduce new computational challenges. Thus, we developed MIA-Sig, an algorithmic solution based on signal processing and information theory. We demonstrate its ability to de-noise the multiplex data, assess the statistical significance of chromatin complexes, and identify topological domains and frequent inter-domain contacts. On chromatin immunoprecipitation (ChIP)-enriched data, MIA-Sig can clearly distinguish the protein-associated interactions from the non-specific topological domains. Together, MIA-Sig represents a novel algorithmic framework for multiplex chromatin interaction analysis.

MATCHA: Probing Multi-way Chromatin Interaction with Hypergraph Representation Learning

“…4dnucleome.org. We downloaded the processed RNAPII enriched ChIA-Drop data and ChIA-Drop data of Drosophila S2 cell from GSE109355 (Zheng et al, 2019). When creating the contact matrix for the SPRITE data, we used the same procedure in Qui-…”

“…The SPRITE data are from the GM12878 lymphoblastoid human cell line (Quinodoz et al, 2018). The RNAPII enriched ChIA-Drop data are from Drosophila S2 cells (Zheng et al, 2019). Unless otherwise stated, we used 1-Mb resolution for the SPRITE data and 5-kb resolution for the RNAPII ChIA-Drop data to build the hypergraphs.…”

“…Next, we generated the denoised contact map for the ChIA-Drop data at 20-kb resolution. Here, we used the ChIA-Drop data without ChIP enrichment (data from Zheng et al, 2019) to compare with the Hi-C data for Drosophila S2R+ (Szabo et al, 2018). Specifically, we compared the denoising results with a recently published ChIA-Drop denoising method, MIA-Sig .…”

“…Based on the SPRITE data, Quinodoz et al (2018) reported that the inter-chromosomal chromatin interactions can be partitioned into distinct active and inactive hubs. ChIA-Drop, on the other hand, allows the detection of multi-way chromatin interactions mediated by specific proteins (Zheng et al, 2019). For example, from RNA PolII ChIA-Drop data, potential co-regulated genes can be characterized.…”

“…For example, from RNA PolII ChIA-Drop data, potential co-regulated genes can be characterized. These recently developed methods have demonstrated unique properties of the 3D genome architecture that can only be manifested by multi-way chromatin interactions (Beagrie et al, 2017;Quinodoz et al, 2018;Zheng et al, 2019).…”