TY - JOUR T1 - A computational platform for high-throughput analysis of RNA sequences and modifications by mass spectrometry JF - bioRxiv DO - 10.1101/501668 SP - 501668 AU - Samuel Wein AU - Byron Andrews AU - Timo Sachsenberg AU - Helena Santos-Rosa AU - Oliver Kohlbacher AU - Tony Kouzarides AU - Benjamin A. Garcia AU - Hendrik Weisser Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/12/20/501668.abstract N2 - The field of epitranscriptomics is growing in importance, with chemical modification of RNA being associated with a wide variety of biological phenomena. A pivotal challenge in this area is the identification of modified RNA residues within their sequence contexts. Next-generation sequencing approaches are generally unable to capture modifications, although workarounds for some epigenetic marks exist. Mass spectrometry (MS) offers a comprehensive solution by using analogous approaches to shotgun proteomics. However, software support for the analysis of RNA MS data is inadequate at present and does not allow high-throughput processing. In particular, existing software solutions lack the raw performance and statistical grounding to efficiently handle the large variety of modifications present on RNA. We present a free and open-source database search engine for RNA MS data, called NucleicAcidSearchEngine (NASE), that addresses these shortcomings. We demonstrate the capability of NASE to reliably identify a wide range of modified RNA sequences in three original datasets of varying complexity. In a human tRNA sample, we characterize over 20 different modification types simultaneously and find many cases of incomplete modification. ER -