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A comparison of topologically associating domain callers over mammals at high resolution

Title	A comparison of topologically associating domain callers over mammals at high resolution
Author	Sefer, Emre
Publication Date:	2022-04-12
Publication Place	- BioMed Central Ltd
Subject	Chromatin organization, Hi-C, Micro-C, TAD callers, Topologically associating domains
Type	Periodical
Language	English
Digital	Yes
Manuscript	No
Library:	Özyeğin University
Library Asset ID	1471-2105
Record ID	8796860d-197d-456a-a130-4abcad41a98b
Library Location	Computer Science
Date	2022-04-12
Sample Text	Background: Topologically associating domains (TADs) are locally highly-interacting genome regions, which also play a critical role in regulating gene expression in the cell. TADs have been first identified while investigating the 3D genome structure over High-throughput Chromosome Conformation Capture (Hi-C) interaction dataset. Substantial degree of efforts have been devoted to develop techniques for inferring TADs from Hi-C interaction dataset. Many TAD-calling methods have been developed which differ in their criteria and assumptions in TAD inference. Correspondingly, TADs inferred via these callers vary in terms of both similarities and biological features they are enriched in. Result: We have carried out a systematic comparison of 27 TAD-calling methods over mammals. We use Micro-C, a recent high-resolution variant of Hi-C, to compare TADs at a very high resolution, and classify the methods into 3 categories: feature-based methods, Clustering methods, Graph-partitioning methods. We have evaluated TAD boundaries, gaps between adjacent TADs, and quality of TADs across various criteria. We also found particularly CTCF and Cohesin proteins to be effective in formation of TADs with corner dots. We have also assessed the callers performance on simulated datasets since a gold standard for TADs is missing. TAD sizes and numbers change remarkably between TAD callers and dataset resolutions, indicating that TADs are hierarchically-organized domains, instead of disjoint regions. A core subset of feature-based TAD callers regularly perform the best while inferring reproducible domains, which are also enriched for TAD related biological properties. Conclusion: We have analyzed the fundamental principles of TAD-calling methods, and identified the existing situation in TAD inference across high resolution Micro-C interaction datasets over mammals. We come up with a systematic, comprehensive, and concise framework to evaluate the TAD-calling methods performance across Micro-C datasets. Our research will be useful in selecting appropriate methods for TAD inference and evaluation based on available data, experimental design, and biological question of interest. We also introduce our analysis as a benchmarking tool with publicly available source code.
DOI	10.1186/s12859-022-04674-2
Cilt	23

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A comparison of topologically associating domain callers over mammals at high resolution

Author Sefer, Emre

Publication Date 2022-04-12

Publication Place - BioMed Central Ltd

Subject Chromatin organization, Hi-C, Micro-C, TAD callers, Topologically associating domains

Type Periodical

Language English

Digital Yes

Manuscript No

Library Özyeğin University

Library Asset ID 1471-2105

Record ID 8796860d-197d-456a-a130-4abcad41a98b

Library Location Computer Science

Date 2022-04-12

Sample Text Background: Topologically associating domains (TADs) are locally highly-interacting genome regions, which also play a critical role in regulating gene expression in the cell. TADs have been first identified while investigating the 3D genome structure over High-throughput Chromosome Conformation Capture (Hi-C) interaction dataset. Substantial degree of efforts have been devoted to develop techniques for inferring TADs from Hi-C interaction dataset. Many TAD-calling methods have been developed which differ in their criteria and assumptions in TAD inference. Correspondingly, TADs inferred via these callers vary in terms of both similarities and biological features they are enriched in. Result: We have carried out a systematic comparison of 27 TAD-calling methods over mammals. We use Micro-C, a recent high-resolution variant of Hi-C, to compare TADs at a very high resolution, and classify the methods into 3 categories: feature-based methods, Clustering methods, Graph-partitioning methods. We have evaluated TAD boundaries, gaps between adjacent TADs, and quality of TADs across various criteria. We also found particularly CTCF and Cohesin proteins to be effective in formation of TADs with corner dots. We have also assessed the callers performance on simulated datasets since a gold standard for TADs is missing. TAD sizes and numbers change remarkably between TAD callers and dataset resolutions, indicating that TADs are hierarchically-organized domains, instead of disjoint regions. A core subset of feature-based TAD callers regularly perform the best while inferring reproducible domains, which are also enriched for TAD related biological properties. Conclusion: We have analyzed the fundamental principles of TAD-calling methods, and identified the existing situation in TAD inference across high resolution Micro-C interaction datasets over mammals. We come up with a systematic, comprehensive, and concise framework to evaluate the TAD-calling methods performance across Micro-C datasets. Our research will be useful in selecting appropriate methods for TAD inference and evaluation based on available data, experimental design, and biological question of interest. We also introduce our analysis as a benchmarking tool with publicly available source code.

DOI 10.1186/s12859-022-04674-2

Cilt 23