RMDisease V2.0: an updated database of genetic variants that affect RNA modifications with disease and trait implication

Abstract

Recent advances in epitranscriptomics have unveiled functional associations between RNA modifications (RMs) and multiple human diseases, but distinguishing the functional or disease-related single nucleotide variants (SNVs) from the majority of ‘silent’ variants remains a major challenge. We previously developed the RMDisease database for unveiling the association between genetic variants and RMs concerning human disease pathogenesis. In this work, we present RMDisease v2.0, an updated database with expanded coverage. Using deep learning models and from 873 819 experimentally validated RM sites, we identified a total of 1 366 252 RM-associated variants that may affect (add or remove an RM site) 16 different types of RNA modifications (m6A, m5C, m1A, m5U, Ψ, m6Am, m7G, A-to-I, ac4C, Am, Cm, Um, Gm, hm5C, D and f5C) in 20 organisms (human, mouse, rat, zebrafish, maize, fruit fly, yeast, fission yeast, Arabidopsis, rice, chicken, goat, sheep, pig, cow, rhesus monkey, tomato, chimpanzee, green monkey and SARS-CoV-2). Among them, 14 749 disease- and 2441 trait-associated genetic variants may function via the perturbation of epitranscriptomic markers. RMDisease v2.0 should serve as a useful resource for studying the genetic drivers of phenotypes that lie within the epitranscriptome layer circuitry, and is freely accessible at: www.rnamd.org/rmdisease2.

PLP1 may serve as a potential diagnostic biomarker of uterine fibroids

“…The CpG islands around the PLP1 gene promoter were profiled by the UCSC Genome online tool ( https://genome.ucsc.edu/ ). The DNA methylation data of the PLP1 gene was retrieved from the DiseaseMeth version 2.0 database ( http://bio-bigdata.hrbmu.edu.cn/diseasemeth/ ) ( Song et al, 2022 ). The RNA modification type of PLP1 was identified by m6A-atlas ( Tang et al, 2021 ) ( http://rnamd.org/m6a ) and m5C-atlas ( Ma et al, 2022 ) ( http://rnamd.org/m5c-atlas/index.html ).…”

Epitranscriptomics in the development, functions, and disorders of cancer stem cells

“…To fully uncover the association between disease-related variants and their epigenetic transcriptome disturbances, Chen et al established RMDisease, a database of genetic variants that correlate RNA modifications with underlying diseases (193). Recently, the authors have updated RMDisease to RMDiseasev2.0 by collecting all available RM-related variants and annotating their potential participation in diseases and traits (194). Song et al proposed a comprehensive online platform, m6A-TSHub, to reveal m 6 A methylation and m 6 A-relateded mutations in 23 human tissues.…”

RNA Epigenetics in Chronic Lung Diseases

“…The m 6 A2Target is a comprehensive database of target genes for m 6 A modified enzymes (writers, erasers, and readers). Specialized reversible RNA modification databases include m 6 Avar [ 66 ], m 6 A-TSHub [ 67 ], CVm 6 A [ 68 ], RMVar [ 69 ] and RMDisease [ 70 ]. RNA editing databases include RNA Editing Database (REDIdb) [ 71 ], Rigorously Annotated Database of A-to-I RNA Editing (RADAR) [ 72 ], Database of RNA Editing (DARNED) [ 73 ], and REDIportal [ 74 ].…”