Dataset Information

A PTM-centric Proteome Informatic Pipeline for Monitoring Post-Translational Modifications by PEIMAN2

ABSTRACT: Post-translational modifications (PTMs) are under significant focus in molecular biomedicine due to their importance in signal transduction in most cellular and organismal processes. Identification of PTMs, determination of PTM location sites, discrimination between functional and inert PTMs, and quantification of their occupancies are demanding tasks, especially in the light of PTM crosstalk in each biosystem. On top of that, the study of each PTM often necessitates a particular experimental design. Computational approaches can identify the relevant PTMs in a biosystem and help to design follow-up experiments involving specific PTM enrichment. Here, we present a PTM-centric proteome informatic pipeline for prediction of most probable and relevant PTMs in mass spectrometry-based proteomics data and refining raw data search parameters based on the acquired knowledge. Using expression profiling, we identified cellular proteins that are differentially regulated in response to multikinase inhibitors dasatinib and staurosporine at four different concentrations. Computational enrichment analysis was employed to determine the potential PTMs of protein targets for both drugs. Finally, we conducted an additional round of database search with these predicted chemical modifications. Our pipeline helped analyze the enriched PTMs and even detected proteins that were not picked up in the initial search. Our findings support the idea of PTM-oriented searching of MS data in proteomics based on computational enrichment analysis.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Amir Ata Saei

LAB HEAD: Prof. Roman A. Zubarev

PROVIDER: PXD037679 | Pride | 2025-05-06

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	200602_CATCH_Dasatinib_f1.raw	Raw
	200602_CATCH_Dasatinib_f10.raw	Raw
	200602_CATCH_Dasatinib_f11.raw	Raw
	200602_CATCH_Dasatinib_f12.raw	Raw
	200602_CATCH_Dasatinib_f13.raw	Raw

Items per page:

1 - 5 of 33

Publications

Monitoring Functional Posttranslational Modifications Using a Data-Driven Proteome Informatic Pipeline.

Nickchi Payman P Vadadokhau Uladzislau U Mirzaie Mehdi M Baumann Marc M Saei Amir A AA Jafari Mohieddin M

Proteomics 20250318 8

Posttranslational modifications (PTMs) are of significant interest in molecular biomedicine due to their crucial role in signal transduction across various cellular and organismal processes. Characterizing PTMs, distinguishing between functional and inert modifications, quantifying their occupancies, and understanding PTM crosstalk are challenging tasks in any biosystem. Studying each PTM often requires a specific, labor-intensive experimental design. Here, we present a PTM-centric proteome info ...[more]

PMID: 40100226

Similar Datasets

Project description:Both genetic and environmental factors are implicated in Type 1 Diabetes (T1D). Since environmental factors can trigger epigenetic changes, we hypothesized that variations in histone posttranslational modifications (PTMs) at the promoter/enhancer regions of T1D susceptible genes may be associated with T1D. We therefore evaluated histone PTM variations at known T1D susceptible genes in blood cells from T1D patients versus healthy non-diabetic controls, and explored their connections to T1D. We used the chromatin-immunoprecipitation-linked-to-microarray approach to profile key histone PTMs, including H3-lysine-4 trimethylation (H3K4me3), H3K27me3, H3K9me3, H3K9 acetylation (H3K9Ac) and H4K16Ac at genes within the T1D susceptible loci in lymphocytes, and H3K4me3, H3K9me2, H3K9Ac and H4K16Ac at the IDDM1 region in monocytes of T1D patients and healthy controls separately. We screened for potential variations in histone PTMs using computational methods to compare datasets from T1D and controls. Interestingly, we observed marked variations in H3K9Ac levels at the upstream regions of HLA-DRB1 and HLA-DQB1 within the IDDM1 locus in T1D monocytes relative to controls. Additional experiments with THP-1 monocytes demonstrated increased expression of HLA-DRB1 and HLA-DQB1 in response to interferon- and TNF-treatment that were accompanied by changes in H3K9Ac at the same promoter regions as that seen in the patient monocytes. These results suggest that the H3K9Ac status of HLA-DRB1 and HLA-DQB1, two genes highly associated with T1D, may be relevant to their regulation and transcriptional response towards external stimuli. Thus, the promoter/enhancer architecture and chromatin status of key susceptible loci could be important determinants in their functional association to T1D susceptibility. We evaluated histone PTM variations at known T1D susceptible genes in blood cells from T1D patients versus healthy non-diabetic controls, and explored their connections to T1D. We used the ChIP-chip approach to profile key histone PTMs, including histone H3K4me3, H3K27me3, H3K9me3, H3K9 acetylation (H3K9Ac) and H4K16Ac, at genes within the T1D susceptible loci in lymphocytes.