Proteomics

Dataset Information

0

A375 melanoma cell line, Expanded database search comparisons


ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Melanocyte, Skin

SUBMITTER: Joshua Elias  

LAB HEAD: Joshua E. Elias

PROVIDER: PXD005912 | Pride | 2019-03-12

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20151207_ath017216_moda_out.txt Txt
20151214_ath017216_YtoF_moda_out.txt Txt
A375_RPLC_TagGraph_YtoF_unfiltered.txt Txt
A375_RPLC_TagGraph_unfiltered.txt Txt
A375_all_fracs.csv Csv
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Publications

TagGraph reveals vast protein modification landscapes from large tandem mass spectrometry datasets.

Devabhaktuni Arun A   Lin Sarah S   Zhang Lichao L   Swaminathan Kavya K   Gonzalez Carlos G CG   Olsson Niclas N   Pearlman Samuel M SM   Rawson Keith K   Elias Joshua E JE  

Nature biotechnology 20190401 4


Although mass spectrometry is well suited to identifying thousands of potential protein post-translational modifications (PTMs), it has historically been biased towards just a few. To measure the entire set of PTMs across diverse proteomes, software must overcome the dual challenges of covering enormous search spaces and distinguishing correct from incorrect spectrum interpretations. Here, we describe TagGraph, a computational tool that overcomes both challenges with an unrestricted string-based  ...[more]

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