Systematic identification of A-to-I editing associated regulators from multiple human cancers

Gu, T.; Fu, A. Q.; Bolt, M. J.; Zhao, X.

doi:10.1101/812610

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bioRxiv · 10.1101/812610

Systematic identification of A-to-I editing associated regulators from multiple human cancers

Gu, T.·Fu, A. Q.·Bolt, M. J.·Zhao, X.

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Abstract

A-to-I editing is the most common editing type in human that is catalyzed by ADAR family members (ADARs), ADAR1 and ADAR2. Millions of A-to-I editing sites have been discovered recently, however, the regulation mechanisms of the RNA editing process are still not clear. Here we developed a two-step logistic regression model to identify genes that are potentially involved in RNA editing process in four human cancers. The first step by classifying the editing sites into different categories assists the analysis at the second step. In the first step, ADAR1 was identified as the enzyme that associated with the majority of the A-to-I editing sites. Thus, ADAR1 was taken as a control gene in the second step to identify genes that have a stronger effect on editing sites than ADAR1. In addition, the detectable interferons and their receptors were used as covariates in the both steps to account for potential association caused by interferons. Using our advanced method, we successfully found a set of genes that were significantly positively or negatively associated (PA or NA) with specific sets of RNA editing sites. We highlighted two genes, SRSF5 and MIR22HG which were supported by multiple evidences. Most PA and NA genes were unique to each cancer, and only a few shared across two cancers. Pathway enrichment analysis showed that the PA genes from the four cancer types were enriched in Immune System, while the NA genes were enriched in two pathways: Metabolism of RNA, and Metabolism. The functional similarity of the PA and NA genes across all the four cancers indicates that even though most of the editing associated genes were unique to each cancer, they may impact on editing process through common pathways. Interestingly, the PA genes from kidney cancer were enriched for survival-associated genes while the NA genes were depleted of these genes, indicating that the PA genes may play more important roles in kidney cancer development.

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Gu, T., Fu, A. Q., Bolt, M. J., Zhao, X.. 2019-10-21. Systematic identification of A-to-I editing associated regulators from multiple human cancers. https://doi.org/10.1101/812610

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