Dataset Information

A supervised learning framework for chromatin loop detection in genome-wide contact maps.

ABSTRACT: Accurately predicting chromatin loops from genome-wide interaction matrices such as Hi-C data is critical to deepening our understanding of proper gene regulation. Current approaches are mainly focused on searching for statistically enriched dots on a genome-wide map. However, given the availability of orthogonal data types such as ChIA-PET, HiChIP, Capture Hi-C, and high-throughput imaging, a supervised learning approach could facilitate the discovery of a comprehensive set of chromatin interactions. Here, we present Peakachu, a Random Forest classification framework that predicts chromatin loops from genome-wide contact maps. We compare Peakachu with current enrichment-based approaches, and find that Peakachu identifies a unique set of short-range interactions. We show that our models perform well in different platforms, across different sequencing depths, and across different species. We apply this framework to predict chromatin loops in 56 Hi-C datasets, and release the results at the 3D Genome Browser.

SUBMITTER: Salameh TJ

PROVIDER: S-EPMC7347923 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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A supervised learning framework for chromatin loop detection in genome-wide contact maps.

Salameh Tarik J TJ Wang Xiaotao X Song Fan F Zhang Bo B Wright Sage M SM Khunsriraksakul Chachrit C Ruan Yijun Y Yue Feng F

Nature communications 20200709 1

Accurately predicting chromatin loops from genome-wide interaction matrices such as Hi-C data is critical to deepening our understanding of proper gene regulation. Current approaches are mainly focused on searching for statistically enriched dots on a genome-wide map. However, given the availability of orthogonal data types such as ChIA-PET, HiChIP, Capture Hi-C, and high-throughput imaging, a supervised learning approach could facilitate the discovery of a comprehensive set of chromatin interac ...[more]

PMID: 32647330

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Project description:BACKGROUND:The spatial configuration of chromosomes is essential to various cellular processes, notably gene regulation, while architecture related alterations, such as translocations and gene fusions, are often cancer drivers. Thus, eliciting chromatin conformation is important, yet challenging due to compaction, dynamics and scale. However, a variety of recent assays, in particular Hi-C, have generated new details of chromatin structure, spawning a number of novel biological findings. Many findings have resulted from analyses on the level of native contact data as generated by the assays. Alternatively, reconstruction based approaches often proceed by first converting contact frequencies into distances, then generating a three dimensional (3D) chromatin configuration that best recapitulates these distances. Subsequent analyses can enrich contact level analyses via superposition of genomic attributes on the reconstruction. But, such advantages depend on the accuracy of the reconstruction which, absent gold standards, is inherently difficult to assess. Attempts at accuracy evaluation have relied on simulation and/or FISH imaging that typically features a handful of low resolution probes. While newly advanced multiplexed FISH imaging offers possibilities for refined 3D reconstruction accuracy evaluation, availability of such data is limited due to assay complexity and the resolution thereof is appreciably lower than the reconstructions being assessed. Accordingly, there is demand for new methods of reconstruction accuracy appraisal. RESULTS:Here we explore the potential of recently proposed stationary distributions, hereafter StatDns, derived from Hi-C contact matrices, to serve as a basis for reconstruction accuracy assessment. Current usage of such StatDns has focussed on the identification of highly interactive regions (HIRs): computationally defined regions of the genome purportedly involved in numerous long-range intra-chromosomal contacts. Consistent identification of HIRs would be informative with respect to inferred 3D architecture since the corresponding regions of the reconstruction would have an elevated number of k nearest neighbors (kNNs). More generally, we anticipate a monotone decreasing relationship between StatDn values and kNN distances. After initially evaluating the reproducibility of StatDns across replicate Hi-C data sets, we use this implied StatDn - kNN relationship to gauge the utility of StatDns for reconstruction validation, making recourse to both real and simulated examples. CONCLUSIONS:Our analyses demonstrate that, as constructed, StatDns do not provide a suitable measure for assessing the accuracy of 3D genome reconstructions. Whether this is attributable to specific choices surrounding normalization in defining StatDns or to the logic underlying their very formulation remains to be determined.

Dataset Information

A supervised learning framework for chromatin loop detection in genome-wide contact maps.

Publications

A supervised learning framework for chromatin loop detection in genome-wide contact maps.

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