Global Post-Translational Modification Discovery

Li, Qiyao; Shortreed, Michael R.; Wenger, Craig D.; Frey, Brian L.; Schaffer, Leah V.; Scalf, Mark; Smith, Lloyd M.

doi:10.1021/acs.jproteome.6b00034

Cited by 76 publications

(107 citation statements)

References 24 publications

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“…The previously described G-PTM-D search workflow 7 was performed on these high-resolution bottom-up data in the MetaMorpheus software (v0.0.80, available at https://github.com/smith-chem-wisc/MetaMorpheus/releases). The goal of this strategy is to discover protein PTMs that are not present in the UniProt search database.…”

Section: Methodsmentioning

confidence: 99%

“…7 The purpose of the NeuCode SILAC and intact-mass proteomics is to characterize experimentally observed intact proteoforms in E. coli lysate. The purpose of the normal cell culture and bottom-up proteomics is to construct a G-PTM-D database with complete PTM data, which helps proteoform family assembly and identification.…”

Section: Figurementioning

confidence: 99%

“…We recently described a new strategy, Global PTM Discovery (G-PTM-D), for the discovery of PTMs in bottom-up data obtained from unenriched protein digests. 7 Novel PTMs detected in this manner are added to the UniProt database, yielding a new G-PTM-D database. Proteoform Suite uses this augmented database to create a more complete set of theoretical proteoforms, which results in a significant increase in the number of proteoforms identified.…”

Section: Introductionmentioning

confidence: 99%

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Elucidating Escherichia coli Proteoform Families Using Intact-Mass Proteomics and a Global PTM Discovery Database

et al. 2017

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A proteoform family is a group of related molecular forms of a protein (proteoforms) derived from the same gene. We have previously described a strategy to identify proteoforms and elucidate proteoform families in complex mixtures of intact proteins. The strategy is based upon measurements of two properties for each proteoform: (i) the accurate proteoform intact-mass, measured by liquid chromatography/mass spectrometry (LC–MS), and (ii) the number of lysine residues in each proteoform, determined using an isotopic labeling approach. These measured properties are then compared with those extracted from a catalog of theoretical proteoforms containing protein sequences and localized post-translational modifications (PTMs) for the organism under study. A match between the measured properties and those in the catalog constitutes an identification of the proteoform. In the present study, this strategy is extended by utilizing a global PTM discovery database and is applied to the widely studied model organism Escherichia coli, providing the most comprehensive elucidation of E. coli proteoforms and proteoform families to date.

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Section: Methodsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Elucidating Escherichia coli Proteoform Families Using Intact-Mass Proteomics and a Global PTM Discovery Database

et al. 2017

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“…Global PTM Discovery (G‐PTM‐D) is a strategy used by MetaMorpheus to identify PTM‐containing peptides in bottom‐up proteomics. It has been extended to top‐down analysis to identify proteoforms with unknown PTMs.…”

Section: Informatics Tools For Proteoform Identificationmentioning

confidence: 99%

Identification and Quantification of Proteoforms by Mass Spectrometry

et al. 2019

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A proteoform is a defined form of a protein derived from a given gene with a specific amino acid sequence and localized post‐translational modifications. In top‐down proteomic analyses, proteoforms are identified and quantified through mass spectrometric analysis of intact proteins. Recent technological developments have enabled comprehensive proteoform analyses in complex samples, and an increasing number of laboratories are adopting top‐down proteomic workflows. In this review, some recent advances are outlined and current challenges and future directions for the field are discussed.

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“…MM performs a tiered search strategy that is reliant on the recalibration of MS spectra and the GPTMD algorithm. 37 This next generation search engine is capable of searching for, identifying and quantifying hundreds of unknown post-translational modifications with annotated databases on standard desktop Table 4 contains a summary of these results. MM identified 26,477 unique peptides and 6,111 PTMs in these files alone.…”

Section: Post-translational Modification Identification and Analysismentioning

confidence: 99%

The Cannabis Multi-Omics Draft Map Project

Jenkins

Orsburn

2019

Preprint

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Recently we have seen a relaxation of the historic restrictions on the use and subsequent research on the Cannabis plants, generally classified as Cannabis sativa and Cannabis indica. What research has been performed to date has centered on chemical analysis of plant flower products, namely cannabinoids and various terpenes that directly contribute to phenotypic characteristics of the female flowers. In addition, we have seen many groups recently completing genetic profiles of various plants of commercial value. To date, no comprehensive attempt has been made to profile the proteomes of these plants. We report herein our progress on constructing a comprehensive draft map of the Cannabis proteome. To date we have identified over 17,000 potential protein sequences. Unfortunately, no annotated genome of Cannabis plants currently exists. We present a method by which "next generation" DNA sequencing output and shotgun proteomics data can be combined to produce annotated FASTA files, bypassing the need for annotated genetic information altogether in traditional proteomics workflows. The resulting material represents the first comprehensive annotated FASTA for any Cannabis plant. Using this annotated database as reference we can refine our protein identifications, resulting in the confident identification of 13,000 proteins with putative function. Furthermore, we demonstrate that posttranslational modifications play an important role in the proteomes of Cannabis flower, particularly lysine acetylation and protein glycosylation. To facilitate the evolution of analytical investigations into these plant materials, we have created a portal to host resources we have developed from proteomic and metabolomic analysis of Cannabis plant material as well as our results integrating these resources. All data for this project is available to view or download at www.CannabisDraftMap.Org Proteomics is a science dedicated to the creation of comprehensive quantitative snapshots of all the proteins produced by an individual organism, tissue or cell. 1 The term was coined in the 1990s during the efforts to sequence the first complete human genomes. 2 While the technology was in place to complete the human genome draft in 2003, the first two drafts of the human proteome were not completed by teams led by Johns Hopkins and CIPSM researchers until 2014. These two separate and ambitious projects were the composite of thousands of hours of instrument run time utilizing the most sophisticated hardware available at that time. 3,4 Recent advances in mass spectrometry technology now permit the completion of proteome profiles in more practical time. Single celled organisms have been "fully" sequenced in less than an hour, and by use of multi-dimensional chromatography, relatively high coverage human proteomes have been completed in only a few days. 5-7 While much can be learned by sequencing DNA and RNA in a cell, quantifying and sequencing the proteome has distinct advantages as proteins perform physical and enzymatic activities in the cell and ar...

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Global Post-Translational Modification Discovery

Cited by 76 publications

References 24 publications

Elucidating Escherichia coli Proteoform Families Using Intact-Mass Proteomics and a Global PTM Discovery Database

Elucidating Escherichia coli Proteoform Families Using Intact-Mass Proteomics and a Global PTM Discovery Database

Identification and Quantification of Proteoforms by Mass Spectrometry

The Cannabis Multi-Omics Draft Map Project

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