GPS-YNO2: computational prediction of tyrosine nitration sites in proteins

Liu, Zexian; Cao, Jun; Ma, Qian; Gao, Xiaolan; Ren, Jian; Xue, Yu

doi:10.1039/c0mb00279h

Cited by 90 publications

(96 citation statements)

References 39 publications

(97 reference statements)

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“…By collecting 6089 p-sites in 2209 mouse liver proteins (14), we predicted 4502 ssKSRs among the 308 PKs and 543 proteins for 1176 p-sites, with a coverage rate of 19.3% (supplemental Table S17). However, we only detected 13 and 9 PKs with significantly over-or under-represented p-sites with the Yates' chi-squared ( 2 ) test (p value Ͻ 0.01, supplemental Table S18) (41). And the statistical significance is much lower against the result in the human liver PPN (supplemental Table S15).…”

Section: Discussionmentioning

confidence: 91%

Systematic Analysis of Protein Phosphorylation Networks From Phosphoproteomic Data

Song

Liu

et al. 2012

Molecular & Cellular Proteomics

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In eukaryotes, hundreds of protein kinases (PKs) specifically and precisely modify thousands of substrates at specific amino acid residues to faithfully orchestrate numerous biological processes, and reversibly determine the cellular dynamics and plasticity. Although over 100,000 phosphorylation sites (p-sites) have been experimentally identified from phosphoproteomic studies, the regulatory PKs for most of these sites still remain to be characterized. Here, we present a novel software package of iGPS for the prediction of in vivo site-specific kinase-substrate relations mainly from the phosphoproteomic data. By critical evaluations and comparisons, the performance of iGPS is satisfying and better than other existed tools. Based on the prediction results, we modeled protein phosphorylation networks and observed that the eukaryotic phospho-regulation is poorly conserved at the site and substrate levels. With an integrative procedure, we conducted a large-scale phosphorylation analysis of human liver and experimentally identified 9719 psites in 2998 proteins. Using iGPS, we predicted a human liver protein phosphorylation networks containing 12,819 potential site-specific kinase-substrate relations among 350 PKs and 962 substrates for 2633 p-sites. Further statistical analysis and comparison revealed that 127 PKs significantly modify more or fewer p-sites in the liver protein phosphorylation networks against the whole human protein phosphorylation network. The largest data set of the human liver phosphoproteome together with computational analyses can be useful for further experimental consideration. This work contributes to the understanding of phosphorylation mechanisms at the systemic level, and provides a powerful methodology for the general analysis of in vivo post-translational modifications regulating sub-proteomes. Molecular & Cellular

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Section: Discussionmentioning

confidence: 91%

Systematic Analysis of Protein Phosphorylation Networks From Phosphoproteomic Data

Song

Liu

et al. 2012

Molecular & Cellular Proteomics

Self Cite

171

192

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“…(i) Its elements were derived based on the same 546 source proteins used in [27] that contain 1,044 nitrotyrosine sites (see columns 1 and 2 of Supporting Information S1). (ii) Slide a flexible window of amino acids ( Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Each of these datasets contained 1,044 nitrotyrosine peptides and 7,669 non-nitrotyrosine peptides. Note that the sample numbers thus obtained have some minor difference with those in [27]. This is because some proteins originally used in [27] have been removed or replaced in the updated version of the Uni-Prot database.…”

Section: Methodsmentioning

confidence: 99%

iNitro-Tyr: Prediction of Nitrotyrosine Sites in Proteins with General Pseudo Amino Acid Composition

et al. 2014

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Nitrotyrosine is one of the post-translational modifications (PTMs) in proteins that occurs when their tyrosine residue is nitrated. Compared with healthy people, a remarkably increased level of nitrotyrosine is detected in those suffering from rheumatoid arthritis, septic shock, and coeliac disease. Given an uncharacterized protein sequence that contains many tyrosine residues, which one of them can be nitrated and which one cannot? This is a challenging problem, not only directly related to in-depth understanding the PTM’s mechanism but also to the nitrotyrosine-based drug development. Particularly, with the avalanche of protein sequences generated in the postgenomic age, it is highly desired to develop a high throughput tool in this regard. Here, a new predictor called “iNitro-Tyr” was developed by incorporating the position-specific dipeptide propensity into the general pseudo amino acid composition for discriminating the nitrotyrosine sites from non-nitrotyrosine sites in proteins. It was demonstrated via the rigorous jackknife tests that the new predictor not only can yield higher success rate but also is much more stable and less noisy. A web-server for iNitro-Tyr is accessible to the public at http://app.aporc.org/iNitro-Tyr/. For the convenience of most experimental scientists, we have further provided a protocol of step-by-step guide, by which users can easily get their desired results without the need to follow the complicated mathematics that were presented in this paper just for the integrity of its development process. It has not escaped our notice that the approach presented here can be also used to deal with the other PTM sites in proteins.

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“…In the prediction PTM sites, this speci ic problem is particularly prominent due to the sequence diversity. For instance, some motifs are very weak and some are not available without the sequence evolutionary information [30][31][32][33][34][35]. To address this Figure 1: A brief fl owchart template for computational prediction PTM sites.…”

Section: Feature Representationmentioning

confidence: 99%

Opinion Prediction of protein Post-Translational Modification sites: An overview

Hasan¹,

Khatun²

2017

Ann Proteom Bioinform

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BackgroundPost-translational modi ication (PTM) refers to the covalent and enzymatic modi ication of proteins during or after protein biosynthesis. In the protein biosynthesis process, the ribosomal mRNA is translated into polypeptide chains, which may further undergo PTM to form the product of mature protein [1]. PTM is a common biological mechanism of both eukaryotic and prokaryotic organisms, which regulates the protein functions, the proteolytic cleavage of regulatory subunits or the degradation of entire proteins and affects all aspects of cellular life. The PTM of a protein can also determine the cell signaling state, turnover, localization, and interactions with other proteins [2]. Therefore, the analysis of proteins and their PTMs are particularly important for the study of heart disease, cancer, neurodegenerative diseases and diabetes [3,4]. Although the characterization of PTMs gets invaluable insight into the cellular functions in etiological processes, there are still challenges. Technically, the major challenges in studying PTMs are the development of speci ic detection and puri ication methods.The PTMs of proteins have been detected by a variety of experimental techniques including the mass spectrometry (MS) [5,6], liquid chromatography [7], radioactive chemical method [8], chromatin immune precipitation (ChIP) [9], western blotting [10], and eastern blotting [7]. The MS technique is one of the mainstay routes in detecting PTMs in a high-throughput manner. The new MS and capillary liquid chromatography instrumentation have made revolutionary advance in enrichment strategies in our growing knowledge of various PTMs [11]. The last decade of the actual description of many PTMs complexity has emerged through the diverse technologies and thousands of precise modi ication sites can now be identi ied with high con idence [12][13][14][15][16][17][18][19][20]. A similar strategy of fragmentation for PTM identi ication is the beam-type collisioninduced dissociation, also called higher energy collisional dissociation [21]. These types of fragmentation are characterized by the higher activation energy. Most of the fragmentation methods of precursor ions are based on the radical anions or thermal electrons [22]. These methods are advantageous over collisionally activated dissociation methods for detecting the unstable PTMs (e.g. O-GlcNAc and phosphorylation), due to the peptide support fragmentation method is effectively independent of the amino acid sequence [23][24][25]. To date, more than 350 types of PTMs have been experimentally discovered in vivo [26]. The common PTMs are phosphorylation, ubiquitination, succinylation, acetylation, pupylation, sumoylation, glycosylation, and so on. In addition, pupylation referring to the modi ication of lysine residues with a prokaryotic, ubiquitin-like protein (i.e. Pup) is another PTM in bacteria.In general, the experimental analysis of PTMs often requires labor-intensive sample preparations and hazardous or expensive chemical reagents. For instance, in the radioactive...

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GPS-YNO2: computational prediction of tyrosine nitration sites in proteins

Cited by 90 publications

References 39 publications

Systematic Analysis of Protein Phosphorylation Networks From Phosphoproteomic Data

Systematic Analysis of Protein Phosphorylation Networks From Phosphoproteomic Data

iNitro-Tyr: Prediction of Nitrotyrosine Sites in Proteins with General Pseudo Amino Acid Composition

Opinion Prediction of protein Post-Translational Modification sites: An overview

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