Dataset Information

MS-DAP platform for label-free proteomics uncovers optimal workflows in benchmark datasets and increased sensitivity in analysis of Alzheimer's biomarker data

ABSTRACT: In the rapidly moving proteomics field, a diverse patchwork of algorithms for data normalization and differential expression analysis is used by the community. We generated an all-inclusive mass spectrometry downstream analysis pipeline (MS-DAP) that integrates many algorithms for normalization and statistical analyses and produces standardized quality reporting with extensive data visualizations. Second, systematic evaluation of normalization and statistical algorithms on various benchmarking datasets, including additional data generated in this study, suggest best-practices for data analysis. Commonly used approaches for differential testing based on moderated t-statistics are consistently outperformed by more recent statistical models, all integrated in MS-DAP, and we encourage their adoption. Third, we introduced a novel normalization algorithm that rescues deficiencies observed in commonly used normalization methods. Finally, we used the MS-DAP platform to re-analyze a recently published large-scale proteomics dataset of CSF from AD patients. This revealed increased sensitivity, resulting in additional significant target proteins which improved overlap with results reported in related studies and includes a large set of new potential AD biomarkers in addition to previously reported.

INSTRUMENT(S): timsTOF Pro 2

ORGANISM(S): Homo Sapiens (human) Saccharomyces Cerevisiae (baker's Yeast)

TISSUE(S): Hela Cell

SUBMITTER: Frank Koopmans

LAB HEAD: August B. Smit

PROVIDER: PXD036134 | Pride | 2023-03-10

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	210903_EV1106_30SPD_DDA_HeLaYeast_50ng12p5ng_1_S1-B1_1_581.d.zip	Other
	210903_EV1106_30SPD_DDA_HeLaYeast_50ng12p5ng_2_S1-B2_1_582.d.zip	Other
	210903_EV1106_30SPD_DDA_HeLaYeast_50ng12p5ng_3_S1-B3_1_583.d.zip	Other
	210903_EV1106_30SPD_DDA_HeLaYeast_50ng15p625ng_1_S1-C1_1_587.d.zip	Other
	210903_EV1106_30SPD_DDA_HeLaYeast_50ng15p625ng_2_S1-C2_1_588.d.zip	Other

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Publications

MS-DAP Platform for Downstream Data Analysis of Label-Free Proteomics Uncovers Optimal Workflows in Benchmark Data Sets and Increased Sensitivity in Analysis of Alzheimer's Biomarker Data.

Koopmans Frank F Li Ka Wan KW Klaassen Remco V RV Smit August B AB

Journal of proteome research 20221221 2

In the rapidly moving proteomics field, a diverse patchwork of data analysis pipelines and algorithms for data normalization and differential expression analysis is used by the community. We generated a mass spectrometry downstream analysis pipeline (MS-DAP) that integrates both popular and recently developed algorithms for normalization and statistical analyses. Additional algorithms can be easily added in the future as plugins. MS-DAP is open-source and facilitates transparent and reproducible ...[more]

PMID: 36541440

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Project description:HIGHTLIGHTS-Improved protocol for ISF collection using microdialysis and CSF sampling in mice.-Combined LC‒MS/MS proteomics ISF and CSF analyses for the validation and description of potential new AD biomarkers.-ISF proteomics analysis to track disease progression at the neuronal and glial levels.-Identification of new biomarker candidates for Alzheimer’s disease.ABSTRACTBackground: Mass spectrometry (MS)-based cerebrospinal fluid (CSF) proteomics is an important method for discovering biomarkers of neurodegenerative diseases. CSF serves as a reservoir for interstitial fluid (ISF), and extensive communication between the two fluid compartments helps to remove waste products from the brain.New method: We performed proteomic analyses of both CSF and ISF fluid compartments using intracerebral microdialysis to validate and detect novel biomarkers of Alzheimer's disease (AD) in APPtg and C57Bl/6J control mice.Results: We identified up to 625 proteins in ISF and 4,483 proteins in CSF samples. By comparing the biofluid profiles of APPtg and C57Bl/6J mice, we detected 37 and 108 significantly up- and downregulated candidates, respectively. In ISF, 7 highly regulated proteins, such as Gfap, Aldh1l1, Gstm1, and Txn, have already been implicated in AD progression, whereas in CSF, 9 out of 14 highly regulated proteins, such as Apba2, Syt12, Pgs1 and Vsnl1, have also been validated to be involved in AD pathogenesis. In addition, we also detected new interesting regulated proteins related to the control of synapses and neurotransmission (Kcna2, Cacng3, and Clcn6) whose roles as AD biomarkers should be further investigated.Comparison with existing methods: This newly established combined protocol provides better insight into the mutual communication between ISF and CSF as an analysis of tissue or CSF compartments alone.Conclusions: The use of multiple fluid compartments, ISF and CSF, for the detection of their biological communication enables better detection of new promising AD biomarkers.KEYWORDSAlzheimer’s disease, CSF, ISF, proteomics, biomarkers, microdialysis, mass spectrometry, protein identification, neurodegeneration, brain fluids, expression profilesDATA AVAILABILITYDOI: 10.17605/OSF.IO/VWQ58PUBLICATIONS using this dataset:1)Gorska et al. 2024, Journal of Neuroscience Methodshttps://doi.org/10.1016/j.jneumeth.2024.1102392) to come