A computational platform for high-throughput analysis of RNA sequences and modifications by mass spectrometry

Samuel Wein, Byron Andrews, Timo Sachsenberg, Helena Santos-Rosa, Oliver Kohlbacher, Tony Kouzarides, Benjamin A. Garcia, Hendrik Weisser

Go to the profile of Nature Communications
Feb 26, 2019
0
0

Received Date: 11th February 19

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.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.


Go to the profile of Nature Communications

Nature Communications

Nature Research, Springer Nature