Identifying stable communities in Hi-C data using a multifractal null model

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Main Authors: Hedström, Lucas, Martínez, Antón Carcedo, Lizana, Ludvig
Format: Preprint
Published: 2024
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author Hedström, Lucas
Martínez, Antón Carcedo
Lizana, Ludvig
author_facet Hedström, Lucas
Martínez, Antón Carcedo
Lizana, Ludvig
contents Chromosome capture techniques like Hi-C have expanded our understanding of mammalian genome 3D architecture and how it influences gene activity. To analyze Hi-C data sets, researchers increasingly treat them as DNA-contact networks and use standard community detection techniques to identify mesoscale 3D communities. However, there are considerable challenges in finding significant communities because the Hi-C networks have cross-scale interactions and are almost fully connected. This paper presents a pipeline to distil 3D communities that remain intact under experimental noise. To this end, we bootstrap an ensemble of Hi-C datasets representing noisy data and extract 3D communities that we compare with the unperturbed dataset. Notably, we extract the communities by maximizing local modularity (using the Generalized Louvain method), which considers the multifractal spectrum recently discovered in Hi-C maps. Our pipeline finds that stable communities (under noise) typically have above-average internal contact frequencies and tend to be enriched in active chromatin marks. We also find they fold into more nested cross-scale hierarchies than less stable ones. Apart from presenting how to systematically extract robust communities in Hi-C data, our paper offers new ways to generate null models that take advantage of the network's multifractal properties. We anticipate this has a broad applicability to several network applications.
format Preprint
id arxiv_https___arxiv_org_abs_2405_05425
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Identifying stable communities in Hi-C data using a multifractal null model
Hedström, Lucas
Martínez, Antón Carcedo
Lizana, Ludvig
Biological Physics
Molecular Networks
Quantitative Methods
Chromosome capture techniques like Hi-C have expanded our understanding of mammalian genome 3D architecture and how it influences gene activity. To analyze Hi-C data sets, researchers increasingly treat them as DNA-contact networks and use standard community detection techniques to identify mesoscale 3D communities. However, there are considerable challenges in finding significant communities because the Hi-C networks have cross-scale interactions and are almost fully connected. This paper presents a pipeline to distil 3D communities that remain intact under experimental noise. To this end, we bootstrap an ensemble of Hi-C datasets representing noisy data and extract 3D communities that we compare with the unperturbed dataset. Notably, we extract the communities by maximizing local modularity (using the Generalized Louvain method), which considers the multifractal spectrum recently discovered in Hi-C maps. Our pipeline finds that stable communities (under noise) typically have above-average internal contact frequencies and tend to be enriched in active chromatin marks. We also find they fold into more nested cross-scale hierarchies than less stable ones. Apart from presenting how to systematically extract robust communities in Hi-C data, our paper offers new ways to generate null models that take advantage of the network's multifractal properties. We anticipate this has a broad applicability to several network applications.
title Identifying stable communities in Hi-C data using a multifractal null model
topic Biological Physics
Molecular Networks
Quantitative Methods
url https://arxiv.org/abs/2405.05425