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

被引：61

作者：

Wein, Samuel ^{[1
,2
]}

Andrews, Byron ^{[3
]}

Sachsenberg, Timo ^{[4
]}

Santos-Rosa, Helena ^{[5
]}

Kohlbacher, Oliver ^{[2
,4
,6
,7
,8
]}

Kouzarides, Tony ^{[5
]}

Garcia, Benjamin A. ^{[1
]}

Weisser, Hendrik ^{[3
]}

机构：

[1] Univ Penn, Perelman Sch Med, Epigenet Program, Philadelphia, PA 19104 USA

[2] Univ Tubingen, Ctr Bioinformat Tubingen, Tubingen, Germany

[3] STORM Therapeut Ltd, Moneta Bldg,Babraham Res Campus, Cambridge, England

[4] Univ Tubingen, Dept Comp Sci, Appl Bioinformat, Tubingen, Germany

[5] Univ Cambridge, Gurdon Inst, Cambridge, England

[6] Univ Tubingen, Quantitat Biol Ctr, Tubingen, Germany

[7] Max Planck Inst Dev Biol, Biomol Interact, Tubingen, Germany

[8] Univ Hosp Tubingen, Translat Bioinformat, Tubingen, Germany

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

关键词：

SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; METHYLATION; PROTEOMICS; IDENTIFICATION; SOFTWARE; STRESS; OPENMS; YEAST; ACIDS;

D O I：

10.1038/s41467-020-14665-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The field of epitranscriptomics continues to reveal how post-transcriptional modification of RNA affects a wide variety of biological phenomena. A pivotal challenge in this area is the identification of modified RNA residues within their sequence contexts. 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. Existing software solutions lack the raw performance and statistical grounding to efficiently handle the numerous modifications found 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 four original datasets of varying complexity. In human tRNA, we characterize over 20 different modification types simultaneously and find many cases of incomplete modification.

引用

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