Abstract

N4-methylcytosine (4mC) is one of the most important DNA modifications and involved in regulating cell differentiations and gene expressions. The accurate identification of 4mC sites is necessary to understand various biological functions. In this work, we developed a new computational predictor called i4mC-Mouse to identify 4mC sites in the mouse genome. Herein, six encoding schemes of k-space nucleotide composition (KSNC), k-mer nucleotide composition (Kmer), mono nucleotide binary encoding (MBE), dinucleotide binary encoding, electron–ion interaction pseudo potentials (EIIP) and dinucleotide physicochemical composition were explored that cover different characteristics of DNA sequence information. Subsequently, we built six RF-based encoding models and then linearly combined their probability scores to construct the final predictor. Among the six RF-based models, the Kmer, KSNC, MBE, and EIIP encodings are sufficient, which contributed to 10%, 45%, 25%, and 20% of the prediction performance, respectively. On the independent test the i4mC-Mouse predicted the 4mC sites with accuracy and MCC of 0.816 and 0.633, respectively, which were approximately 2.5% and 5% higher than those of the existing method (4mCpred-EL). For experimental biologists, a freely available web application was implemented at http://kurata14.bio.kyutech.ac.jp/i4mC-Mouse/.

Highlights

  • In both prokaryotes and eukaryotes, N4-methylcytosine (4mC), 5-Methylcytosine (5mC), and N6-methyladenine (6 mA) alterations can regulate various functions including genomic imprinting, cell developmental, and gene expressions, and play crucial roles in the genomic diversity [1,2]

  • The 5mC modification is a common type of methylation alteration and well-explored that exemplifies an important role in biological developments [3,4] that are associated by the various diseases such as diabetes, neurological, and cancer [5,6]

  • The computational model employed was constructed by using the random forest (RF) algorithm [33]

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Summary

Introduction

In both prokaryotes and eukaryotes, N4-methylcytosine (4mC), 5-Methylcytosine (5mC), and N6-methyladenine (6 mA) alterations can regulate various functions including genomic imprinting, cell developmental, and gene expressions, and play crucial roles in the genomic diversity [1,2]. The exact dataset of modifications of 4mC sites is still limited due to the shortage of experimental identification approaches. To the best of author’s knowledge, only one predictor is available for the 4mC sites in the mouse genome, named 4mCpred-EL [11].

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