Deep5hmC: Predicting genome-wide 5-Hydroxymethylcytosine landscape via a multimodal deep learning model.
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ABSTRACT:
SUBMITTER: Ma X
PROVIDER: S-EPMC10942288 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
Publications
Deep5hmC: Predicting genome-wide 5-Hydroxymethylcytosine landscape via a multimodal deep learning model.
Ma Xin X Thela Sai Ritesh SR Zhao Fengdi F Yao Bing B Wen Zhexing Z Jin Peng P Zhao Jinying J Chen Li L
bioRxiv : the preprint server for biology 20240306
5-hydroxymethylcytosine (5hmC), a critical epigenetic mark with a significant role in regulating tissue-specific gene expression, is essential for understanding the dynamic functions of the human genome. Using tissue-specific 5hmC sequencing data, we introduce Deep5hmC, a multimodal deep learning framework that integrates both the DNA sequence and the histone modification information to predict genome-wide 5hmC modification. The multimodal design of Deep5hmC demonstrates remarkable improvement i ...[more]
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Project description:Motivation5-Hydroxymethylcytosine (5hmC), a crucial epigenetic mark with a significant role in regulating tissue-specific gene expression, is essential for understanding the dynamic functions of the human genome. Despite its importance, predicting 5hmC modification across the genome remains a challenging task, especially when considering the complex interplay between DNA sequences and various epigenetic factors such as histone modifications and chromatin accessibility.ResultsUsing tissue-specific 5hmC sequencing data, we introduce Deep5hmC, a multimodal deep learning framework that integrates both the DNA sequence and epigenetic features such as histone modification and chromatin accessibility to predict genome-wide 5hmC modification. The multimodal design of Deep5hmC demonstrates remarkable improvement in predicting both qualitative and quantitative 5hmC modification compared to unimodal versions of Deep5hmC and state-of-the-art machine learning methods. This improvement is demonstrated through benchmarking on a comprehensive set of 5hmC sequencing data collected at four developmental stages during forebrain organoid development and across 17 human tissues. Compared to DeepSEA and random forest, Deep5hmC achieves close to 4% and 17% improvement of Area Under the Receiver Operating Characteristic (AUROC) across four forebrain developmental stages, and 6% and 27% across 17 human tissues for predicting binary 5hmC modification sites; and 8% and 22% improvement of Spearman correlation coefficient across four forebrain developmental stages, and 17% and 30% across 17 human tissues for predicting continuous 5hmC modification. Notably, Deep5hmC showcases its practical utility by accurately predicting gene expression and identifying differentially hydroxymethylated regions (DhMRs) in a case-control study of Alzheimer's disease (AD). Deep5hmC significantly improves our understanding of tissue-specific gene regulation and facilitates the development of new biomarkers for complex diseases.Availability and implementationDeep5hmC is available via https://github.com/lichen-lab/Deep5hmC.
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