Abstract

Computational methods to predict Z-DNA regions are in high demand to understand the functional role of Z-DNA. The previous state-of-the-art method Z-Hunt is based on statistical mechanical and energy considerations about B- to Z-DNA transition using sequence information. Z-DNA CHiP-seq experiment results showed little overlap with Z-Hunt predictions implying that sequence information only is not sufficient to explain emergence of Z-DNA at different genomic locations. Adding epigenetic and other functional genomic mark-ups to DNA sequence level can help revealing the functional Z-DNA sites. Here we take advantage of the deep learning approach that can analyze and extract information from large volumes of molecular biology data. We developed a machine learning approach DeepZ that aggregates information from genome-wide maps of epigenetic markers, transcription factor and RNA polymerase binding sites, and chromosome accessibility maps. With the developed model we not only verify the experimental Z-DNA predictions, but also generate the whole-genome annotation, introducing new possible Z-DNA regions, which have not yet been found in experiments and can be of interest to the researchers from various fields.

Highlights

  • After discovery of a standard form of DNA, which is the canonical right-handed B-form, or B-DNA1, other DNA configurations were found to exist

  • It is difficult to predict in advance, which architecture will be best suited for the task of Z-DNA recognition, that is why we tested many different models combining different number of machine learning blocks in order to choose the best model, which will be used for whole-genome annotations

  • We propose a deep learning approach, which uses experimental Z-DNA data for training and learns by aggregating information from sequence, B-Z transition energy, transcriptomics, epigenomics, and chromatin organization levels

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Summary

Introduction

After discovery of a standard form of DNA, which is the canonical right-handed B-form, or B-DNA1, other DNA configurations were found to exist. One of them is a left-handed DNA, termed as Z-DNA, discovered unexpectedly during solving the structure of a crystalline fragment of double-helical D­ NA2. Investigation of the crystalline structure revealed characteristic properties of nucleotides in Z-DNA—a regular alternation of syn and anti base conformations along each strand of the helix. Experimental evidence confirmed presence of Z-DNA regions in v­ iruses3, ­bacteria[4] and m­ ammals[5]. Later Z-DNA was found in y­ east6, ­fly[7], and h­ umans[8,9]

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