Dataset Information

DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery.

ABSTRACT: To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

SUBMITTER: Zhu T

PROVIDER: S-EPMC7646093 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery.

Zhu Tiansheng T Zhu Yi Y Xuan Yue Y Gao Huanhuan H Cai Xue X Piersma Sander R SR Pham Thang V TV Schelfhorst Tim T Haas Richard R G D RRGD Bijnsdorp Irene V IV Sun Rui R Yue Liang L Ruan Guan G Zhang Qiushi Q Hu Mo M Zhou Yue Y Van Houdt Winan J WJ Le Large Tessa Y S TYS Cloos Jacqueline J Wojtuszkiewicz Anna A Koppers-Lalic Danijela D Böttger Franziska F Scheepbouwer Chantal C Brakenhoff Ruud H RH van Leenders Geert J L H GJLH Ijzermans Jan N M JNM Martens John W M JWM Steenbergen Renske D M RDM Grieken Nicole C NC Selvarajan Sathiyamoorthy S Mantoo Sangeeta S Lee Sze S SS Yeow Serene J Y SJY Alkaff Syed M F SMF Xiang Nan N Sun Yaoting Y Yi Xiao X Dai Shaozheng S Liu Wei W Lu Tian T Wu Zhicheng Z Liang Xiao X Wang Man M Shao Yingkuan Y Zheng Xi X Xu Kailun K Yang Qin Q Meng Yifan Y Lu Cong C Zhu Jiang J Zheng Jin'e J Wang Bo B Lou Sai S Dai Yibei Y Xu Chao C Yu Chenhuan C Ying Huazhong H Lim Tony K TK Wu Jianmin J Gao Xiaofei X Luan Zhongzhi Z Teng Xiaodong X Wu Peng P Huang Shi'ang S Tao Zhihua Z Iyer Narayanan G NG Zhou Shuigeng S Shao Wenguang W Lam Henry H Ma Ding D Ji Jiafu J Kon Oi L OL Zheng Shu S Aebersold Ruedi R Jimenez Connie R CR Guo Tiannan T

Genomics, proteomics & bioinformatics 20200401 2

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to s ...[more]

PMID: 32795611

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Project description:BackgroundAstrocytes are the most abundant cells in the central nervous system and are responsible for a wide range of functions critical to normal neuronal development, synapse formation, blood-brain barrier regulation, and brain homeostasis. They are also actively involved in initiating and perpetuating neuroinflammatory responses. However, information about their proteomic phenotypes under inflammation is currently limited.MethodData-independent acquisition mass spectrometry was applied to extensively characterize the profile of more than 4000 proteins in immortalized human fetal astrocytes under distinct inflammatory conditions induced by TNF, IL-1β, and LPS, while multiplex immunoassay-based screening was used to quantify a wide range of cytokines released under these inflammatory conditions. Then, immunocytochemistry and western blotting were used to verify the activation of canonical and non-canonical NF-κB upon exposure to the different stimuli. Finally, an in vitro model of the blood-brain barrier consisting of a co-culture of primary human brain microvascular endothelial cells and primary human astrocytes was used to verify the inflammatory response of astrocytes upon LPS exposure in a more complex in vitro system.ResultsWe reported on a set of 186 proteins whose levels were significantly modulated by TNF, IL-1β, and LPS. These three stimuli induced proteome perturbations, which led to an increased abundance of key inflammatory proteins involved in antigen presentation and non-canonical NF-κB pathways. TNF and IL-1β, but not LPS, also activated the canonical NF-κB pathway, which in turn led to an extensive inflammatory response and dysregulation of cytoskeletal and adhesion proteins. In addition, TNF and LPS, but not IL-1β, increased the abundance of several interferon-stimulated gene products. Finally, TNF and IL-1β similarly upregulated the secretion of several cytokines and chemokines, whereas LPS only induced a moderate increase in IL-8, IFN-γ, and IL-1β secretion. Upregulation of proteins associated with type I IFN and non-canonical NF-κB signaling was also observed in primary astrocytes co-cultured with primary brain microvascular endothelial cells exposed to LPS.ConclusionsThe present study provides comprehensive information about the proteomic phenotypes of human astrocytes upon exposure to inflammatory stimuli both in monoculture and in co-culture with human brain microvascular endothelial cells.

Dataset Information

DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery.

Publications

DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery.

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