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DNAcycP: a deep learning tool for DNA cyclizability prediction

Keren Li, Matthew S. Carroll, Reza Vafabakhsh, Xiaozhong A Wang, Ji-Ping Wang

2022Nucleic Acids Research47 citationsDOIOpen Access PDF

Abstract

DNA mechanical properties play a critical role in every aspect of DNA-dependent biological processes. Recently a high throughput assay named loop-seq has been developed to quantify the intrinsic bendability of a massive number of DNA fragments simultaneously. Using the loop-seq data, we develop a software tool, DNAcycP, based on a deep-learning approach for intrinsic DNA cyclizability prediction. We demonstrate DNAcycP predicts intrinsic DNA cyclizability with high fidelity compared to the experimental data. Using an independent dataset from in vitro selection for enrichment of loopable sequences, we further verified the predicted cyclizability score, termed C-score, can well distinguish DNA fragments with different loopability. We applied DNAcycP to multiple species and compared the C-scores with available high-resolution chemical nucleosome maps. Our analyses showed that both yeast and mouse genomes share a conserved feature of high DNA bendability spanning nucleosome dyads. Additionally, we extended our analysis to transcription factor binding sites and surprisingly found that the cyclizability is substantially elevated at CTCF binding sites in the mouse genome. We further demonstrate this distinct mechanical property is conserved across mammalian species and is inherent to CTCF binding DNA motif.

Topics & Concepts

BiologyNucleosomeDNAComputational biologyGenomeCTCFGeneticsDNA sequencingDNA binding siteHMG-boxTranscription factorDNA-binding proteinHistoneGenePromoterEnhancerGene expressionGenomics and Chromatin DynamicsRNA and protein synthesis mechanismsBacterial Genetics and Biotechnology
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