RT Journal Article
SR Electronic
T1 Measuring proteomes with long strings: A new, unconstrained paradigm in mass spectrum interpretation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 282624
DO 10.1101/282624
A1 Arun Devabhaktuni
A1 Niclas Olsson
A1 Carlos Gonzales
A1 Keith Rawson
A1 Kavya Swaminathan
A1 Joshua E. Elias
YR 2018
UL http://biorxiv.org/content/early/2018/03/15/282624.abstract
AB Thousands of protein post-translational modifications (PTMs) dynamically impact nearly all cellular functions. Mass spectrometry is well suited to PTM identification, but proteome-scale analyses are biased towards PTMs with existing enrichment methods. To measure the full landscape of PTM regulation, software must overcome two fundamental challenges: intractably large search spaces and difficulty distinguishing correct from incorrect identifications. Here, we describe TagGraph, software that overcomes both challenges with a string-based search method orders of magnitude faster than current approaches, and probabilistic validation model optimized for PTM assignments. When applied to a human proteome map, TagGraph tripled confident identifications while revealing thousands of modification types on nearly one million sites spanning the proteome. We expand known sites by orders of magnitude for highly abundant yet understudied PTMs such as proline hydroxylation, and derive tissue-specific insight into these PTMs’ roles. TagGraph expands our ability to survey the full landscape of PTM function and regulation.