DNAcycP: a deep learning tool for DNA cyclizability prediction

Author:

Li Keren12,Carroll Matthew3,Vafabakhsh Reza4,Wang Xiaozhong A42,Wang Ji-Ping12ORCID

Affiliation:

1. Department of Statistics, Northwestern University, 633 Clark Street, Evanston, IL 60208, USA

2. NSF-Simons Center for Quantitative Biology, Northwestern University, Evanston, IL 60208, USA

3. Weinberg College IT Solutions (WITS), Northwestern University, 633 Clark Street, Evanston, IL 60208, USA

4. Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA

Abstract

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.

Funder

NSF

Simons Center for Quantitative Biology

National Science Foundation

Publisher

Oxford University Press (OUP)

Subject

Genetics

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