Abstract

Introduction: Driver mutations play a critical role in the occurrence and development of human cancers. Most studies have focused on missense mutations that function as drivers in cancer. However, accumulating experimental evidence indicates that synonymous mutations can also act as driver mutations. Methods: Here, we proposed a computational method called PredDSMC to accurately predict driver synonymous mutations in human cancers. We first systematically explored four categories of multimodal features, including sequence features, splicing features, conservation scores, and functional scores. Further feature selection was carried out to remove redundant features and improve the model performance. Finally, we utilized the random forest classifier to build PredDSMC. Results: The results of two independent test sets indicated that PredDSMC outperformed the state-of-the-art methods in differentiating driver synonymous mutations from passenger mutations. Discussion: In conclusion, we expect that PredDSMC, as a driver synonymous mutation prediction method, will be a valuable method for gaining a deeper understanding of synonymous mutations in human cancers.

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