N6-methyladenosine (m6A) is an abundant modification on mRNA that plays an important role in regulating essential RNA activities. Several wet lab studies have identified some RNA binding proteins (RBPs) that are related to m6A's regulation. The objective of this study was to identify potential m6A-associated RBPs using an integrative computational framework. The framework was composed of an enrichment analysis and a classification model. Utilizing RBPs' binding data, we analyzed reproducible m6A regions from independent studies using this framework. The enrichment analysis identified known m6A-associated RBPs including YTH domain-containing proteins; it also identified RBM3 as a potential m6A-associated RBP for mouse. Furthermore, a significant correlation for the identified m6A-associated RBPs is observed at the protein expression level rather than the gene expression level. On the other hand, a Random Forest classification model was built for the reproducible m6A regions using RBPs' binding data. The RBP-based predictor demonstrated not only competitive performance when compared with sequence-based predictions but also reflected m6A's action of repelling against RBPs, which suggested that our framework can infer interaction between m6A and m6A-associated RBPs beyond sequence level when utilizing RBPs' binding data. In conclusion, we designed an integrative computational framework for the identification of known and potential m6A-associated RBPs. We hope the analysis will provide more insights on the studies of m6A and RNA modifications.
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