M1ARegpred: Epitranscriptome Target Prediction of N1-methyladenosine (m1A) Regulators Based on Sequencing Features and Genomic Features

Abstract

Background: N1-methyladenosine (m1A) is a reversible post-transcriptional modification in mRNA, which has been proved to play critical roles in various biological processes through interaction with different m1A regulators. There are several m1A regulators existing in the human genome, including YTHDF1-3 and YTHDC1. Methods: Several techniques have been developed to identify the substrates of m1A regulators, but their binding specificity and biological functions are not yet fully understood due to the limitations of wetlab approaches. Here, we submitted the framework m1ARegpred (m1A regulators substrate prediction), which is based on machine learning and the combination of sequence-derived and genome-derived features. Results: Our framework achieved area under the receiver operating characteristic (AUROC) scores of 0.92 in the full transcript model and 0.857 in the mature mRNA model, showing an improvement compared to the existing sequence-derived methods. In addition, motif search and gene ontology enrichment analysis were performed to explore the biological functions of each m1A regulator. Conclusions: Our work may facilitate the discovery of m1A regulators substrates of interest, and thereby provide new opportunities to understand their roles in human bodies.

Dynamic regulation and key roles of ribonucleic acid methylation

“… Yao et al (2022) built the framework m1ARegpred (m1A regulators substrate prediction), m1ARegpred was achieved based on ML and the combination of sequence-derived and genome-derived features. Suleman and Khan (2022) developed an extreme gradient boost predictor named as m1A-Pred for the prediction of modified m1A sites.…”

Novel insight into RNA modifications in tumor immunity: Promising targets to prevent tumor immune escape

“… Yao et al. 133 iRNA-m5C m 5 C RF http://lin-group.cn/server/iRNA-m5C/service.html Lv et al. 229 RNAm5Cfinder m 5 C RF http://www.rnanut.net/rnam5cfinder Li et al.…”

“… 131 However, in contrast to the m 6 A modification, which preferentially decorates stop codons and 3′ UTRs, the m 1 A modification is enriched mainly on start codons upstream of the first splice site and 5′ UTRs of mRNA transcripts. 131 , 132 M1ARegpred 133 and RAMPred 134 are powerful tools for predicting m 1 A modification sites ( Table 3 ).…”

Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain

“…Although overall discovery and characterization of the writer and eraser proteins is important for understanding the regulatory networks of these modified RNAs (reviewed in [13] , [27] ), this minireview focuses on the reader proteins of m 6 A, m 1 A, N5-methylcytosine (m 5 C), and 8-oxo-7,8-dihydroguanosine (8-oxoG) [28] , [29] , [30] . Additionally, we acknowledge the numerous works to characterize the RNA sequence specificity of these protein readers [16] , [31] , [32] , [33] , [34] but limit our discussion to the biophysical investigations of protein-RNA interactions specific to modified RNA. To that end, we showcase the mechanistic understanding of protein interactions with the epitranscriptome that has been generated using both experimental and computational techniques.…”