Three-dimensional Epigenome Statistical Model: Genome-wide Chromatin Looping Prediction

TLDR

The complex signatures of epigenomic and transcription factors within physically interacting chromatin regions are similar across genomic scales, cell types, and individuals. The study aims to uncover the biophysical mechanisms underlying three‑dimensional epigenome folding using statistical learning. The 3DEpiLoop algorithm predicts chromatin looping interactions within topologically associating domains from one‑dimensional epigenomic and transcription factor profiles via statistical learning. The predictions are highly consistent with experimental interactions, and the analysis identifies key epigenetic and transcription factor features—shared or cell‑line specific—that drive interaction identification, with CTCF anchors enriched in transcription factors but low in histone modifications, whereas RNAP II interactions show the opposite pattern. The code is available at https://bitbucket.org/4dnucleome/3depiloop.

Abstract

Abstract This study aims to understand through statistical learning the basic biophysical mechanisms behind three-dimensional folding of epigenomes. The 3DEpiLoop algorithm predicts three-dimensional chromatin looping interactions within topologically associating domains (TADs) from one-dimensional epigenomics and transcription factor profiles using the statistical learning. The predictions obtained by 3DEpiLoop are highly consistent with the reported experimental interactions. The complex signatures of epigenomic and transcription factors within the physically interacting chromatin regions (anchors) are similar across all genomic scales: genomic domains, chromosomal territories, cell types, and different individuals. We report the most important epigenetic and transcription factor features used for interaction identification either shared, or unique for each of sixteen (16) cell lines. The analysis shows that CTCF interaction anchors are enriched by transcription factors yet deficient in histone modifications, while the opposite is true in the case of RNAP II mediated interactions. The code is available at the repository https://bitbucket.org/4dnucleome/3depiloop .