Identifying modifications on DNA-bound histones with joint deep learning of multiple binding sites in DNA sequence.

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Abstract

Histone modifications are epigenetic markers that impact gene expression by altering the chromatin structure or recruiting histone modifiers. Their accurate identification is key to unraveling the mechanisms by which they regulate gene expression. However, the solutions for this task can be improved by exploiting multiple relationships from dataset and exploring designs of learning models, e.g. jointly learning technology.This paper proposes a deep learning-based multi-objective computational approach, iHMnBS, to identify which of the seven typical histone modifications a DNA sequence may choose to bind, and which parts of the DNA sequence bind to them. iHMnBS employs a customized dataset that allows the marking of modifications contained in histones that may bind to any position in the DNA sequence. iHMnBS tries to mine the information implicit in this richer data by means of deep neural networks. In comprehensive comparisons, iHMnBS outperforms a baseline method, and the probability of binding to modified histones assigned to a representative nucleotide of a DNA sequence can serve as a reference for biological experiments. Since the interaction between transcription factors (TFs) and histone modifications has an important role in gene expression, we extracted a number of sequence patterns that may bind to TFs, and explored their possible impact on disease.The source code is available at https://github.com/lennylv/iHMnBS.Supplementary data are available at Bioinformatics online.© The Author(s) (2022). Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].