The Cancer Editome Atlas: A Resource for Exploratory Analysis of the Adenosine-to-Inosine RNA Editome in Cancer

Abstract

Increasing evidence has suggested a role for adenosine-toinosine RNA editing in carcinogenesis. However, the clinical utility of RNA editing remains limited because functions of the vast majority of editing events remain largely unexplored. To help the cancer research community investigate functional consequences of individual editing events, we have developed a user-friendly bioinformatic resource, The Cancer Editome Atlas (TCEA; http://tcea.tmu.edu.tw). TCEA characterizes >192 million editing events at >4.6 million editing sites from approximately 11,000 samples across 33 cancer types in The Cancer Genome Atlas. Clinical information, miRNA expression , and alteration in miRNA targeting modulated through RNA editing are also integrated into TCEA. TCEA supports several modules to search, analyze, and visualize the cancer editome, providing a solid basis for investigating the oncogenic mechanisms of RNA editing and expediting the identification of therapeutic targets in cancer. Significance: This user-friendly bioinformatic resource reduces the barrier to analyzing the huge and complex cancer RNA editome that cancer researchers face and facilitates the identification of novel therapeutic targets in cancer.

Quantifying RNA Editing in Deep Transcriptome Datasets

“…Editing dysregulation at recoding sites between two groups of samples is often assayed applying the twotailed MW U-test followed by Benjamin-Hochberg multiple test corrections. For example, such an approach was used to identify many recoding sites differentially edited in cancer compared with normal samples (Maas et al, 2001;Paz et al, 2007;Cenci et al, 2008;Chen et al, 2013;Qin et al, 2014;Han et al, 2015;Paz-Yaacov et al, 2015;Hu et al, 2016;Lin and Chen, 2019;Silvestris et al, 2019). Here, we demonstrate this approach by detecting statistically significant differentially recoded sites between 14 artery tibial and 12 cerebellum samples, looking at 1585 nonsynonymous REDIportal positions quantified using REDItools.…”

“…In the specialized database REDIportal (Picardi et al, 2016), for example, REDItools have been used to interrogate multiple read alignments from 2660 GTEx RNAseq experiments employing a large collection of known RNA editing sites from the ATLAS repository (Picardi et al, 2015b) and DARNED database (Kiran et al, 2013). Another example is The Cancer RNA Editome Atlas (TCEA) (Lin and Chen, 2019), where REDIportal positions (4,656,896) have been explored in more than 11,000 RNAseq data from the TCGA project (Cancer Genome Atlas Research Network et al, 2013).…”

MiREDiBase: a manually curated database of validated and putative editing events in microRNAs

“…Cancer Editome Atlas (TCEA) is a powerful, user-friendly bioinformatics resource that characterizes more than 192 million editing events at ~4.6 million editing sites from approximately 11,000 samples across 33 cancer types recovered from The Cancer Genome Atlas (Lin and Chen 2019). However, to the same extent as the previously mentioned resources, TCEA is mainly focused on editing events occurring in mRNAs.…”

“…Given the extensive number of high-confidence RNA editing sites identified so far and their established complex resources such as TCEA (Lin and Chen 2019) are well known. However, no dedicated online resources have been explicitly implemented for the study of miRNA editing until now.…”

MultiEditR: An easy validation method for detecting and quantifying RNA editing from Sanger sequencing

“…Indeed knock out mice for ADAR1 or ADAR2 have lethal phenotypes (Hartner et al 2004;Wang et al 2004;Ward et al 2010) and knock out mice for APOBEC1 exhibit myelin fragmentation and lysosome/autophagosome accumulation in microglia and neurons, leading to an early-aging phenotype characterized by cognitive and motor deficits (Cole et al 2017). Additionally, A-to-I RNA editing is the most abundant modification in mRNA (Picardi et al 2017;Ramaswami and Li 2014) both in healthy tissues and during oncogenesis and tumour progression (Fumagalli et al 2015;Galeano et al 2012;Han et al 2015;Lin and Chen 2019;Paz-Yaacov et al 2015;Xu and Öhman 2019).…”