Mass spectrometry‐based high‐throughput proteomics and its role in biomedical studies and systems biology

Messner, Christoph B.; Demichev, Vadim; Wang, Ziyue; Hartl, Johannes; Kustatscher, Georg; Mülleder, Michael; Ralser, Markus

doi:10.1002/pmic.202200013

Cited by 36 publications

(20 citation statements)

References 187 publications

(331 reference statements)

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“…Proteins play important roles in various cellular activities. They can reflect the state of the body, and provide insights into the molecular changes (23,24). Therefore We established a model of sepsis-induced renal injury in mice and performed protein spectrum detection and bioinformatics analysis to explore the mechanism underlying AKI.…”

Section: Discussionmentioning

confidence: 99%

CTSB promotes sepsis-induced acute kidney injury through activating mitochondrial apoptosis pathway

Wang

Xi²,

Zhang³

et al. 2023

Front. Immunol.

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BackgroundAcute kidney injury is a common and severe complication of sepsis. Sepsis -induced acute kidney injury(S-AKI) is an independent risk factor for mortality among sepsis patients. However, the mechanisms of S-AKI are complex and poorly understand. Therefore, exploring the underlying mechanisms of S-AKI may lead to the development of therapeutic targets.MethodA model of S-AKI was established in male C57BL/6 mice using cecal ligation and puncture (CLP). The data-independent acquisition (DIA)-mass spectrometry-based proteomics was used to explore the protein expression changes and analyze the key proteomics profile in control and CLP group. The methodology was also used to identify the key proteins and pathways. S-AKI in vitro was established by treating the HK-2 cells with lipopolysaccharide (LPS). Subsequently, the effect and mechanism of Cathepsin B (CTSB) in inducing apoptosis in HK-2 cells were observed and verified.ResultsThe renal injury scores, serum creatinine, blood urea nitrogen, and kidney injury molecule 1 were higher in septic mice than in non-septic mice. The proteomic analysis identified a total of 449 differentially expressed proteins (DEPs). GO and KEGG analysis showed that DEPs were mostly enriched in lysosomal-related cell structures and pathways. CTSB and MAPK were identified as key proteins in S-AKI. Electron microscopy observed enlarged lysosomes, swelled and ruptured mitochondria, and cytoplasmic vacuolization in CLP group. TUNEL staining and CTSB activity test showed that the apoptosis and CTSB activity were higher in CLP group than in control group. In HK-2 cell injury model, the CTSB activity and mRNA expression were increased in LPS-treated cells. Acridine orange staining showed that LPS caused lysosomal membrane permeabilization (LMP). CA074 as an inhibitor of CTSB could effectively inhibit CTSB activity. CCK8 and Annexin V/PI staining results indicated that CA074 reversed LPS-induced apoptosis of HK-2 cells. The JC-1 and western blot results showed that LPS inhibited mitochondrial membrane potential and activated mitochondrial apoptosis pathway, which could be reversed by CA074.ConclusionsLMP and CTSB contribute to pathogenesis of S-AKI. LPS treatment induced HK-2 cell injury by activating mitochondrial apoptosis pathway. Inhibition of CTSB might be a new therapeutic strategy to alleviate sepsis-induced acute kidney injury.

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Section: Discussionmentioning

confidence: 99%

CTSB promotes sepsis-induced acute kidney injury through activating mitochondrial apoptosis pathway

Wang

Xi²,

Zhang³

et al. 2023

Front. Immunol.

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“…In plasma proteomics, throughput and robustness of the workflow are of particular relevance, allowing to scale up the studies, leading to statistical confidence and better performance of machine learning models 1,5,6,[23][24][25][26][27][28] . Moreover, human blood plasma is a matrix that differs quite substantially from the one of a cellular protein extract.…”

Section: Comprehensive Profiling Of Neat Human Plasma Of a Covid-19 I...mentioning

confidence: 99%

Speedy-PASEF: Analytical flow rate chromatography and trapped ion mobility for deep high-throughput proteomics

Szyrwiel

Gille

Mülleder

et al. 2023

Preprint

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Increased throughput in proteomic experiments can improve accessibility of proteomic platforms, reduce costs and facilitate new approaches in systems biology and biomedical research. Here we propose Speedy-PASEF, a combination of analytical flow rate chromatography with ion mobility separation of peptide ions, data-independent acquisition and data analysis with the DIA-NN software suite, for conducting fast, high-quality proteomic experiments that require only moderate sample amounts. For instance, using a 500-μl/min flow rate and a 3-minute chromatographic gradient, Speedy-PASEF quantified 5,211 proteins from 2 μg of a mammalian cell-line standard at high quantitative accuracy and precision. We further used Speedy-PASEF to analyze blood plasma samples from a cohort of COVID-19 inpatients, using a 3-minute chromatographic gradient and alternating column regeneration on a dual pump system, for processing 398 samples per day. Speedy-PASEF delivered a comprehensive view of the COVID-19 plasma proteome, allowing classification of the patients according to disease severity and revealing plasma biomarker candidates. Speedy-PASEF thus facilitates acquisition of high-quality proteomes in large numbers.

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“…Proteomics and metabolomics represent fields that have grown significantly in the last decades, thanks to the important technological advances that allow accurate and sensitive analyses. Both approaches have been extensively used for biomarker discovery in various disorders (26)(27)(28)(29)(30)(31).…”

Section: Proteomic and Metabolomic Approaches For Biomarker Discoverymentioning

confidence: 99%

Endometrial cancer diagnostic and prognostic algorithms based on proteomics, metabolomics, and clinical data: a systematic review

et al. 2023

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Endometrial cancer is the most common gynaecological malignancy in developed countries. Over 382,000 new cases were diagnosed worldwide in 2018, and its incidence and mortality are constantly rising due to longer life expectancy and life style factors including obesity. Two major improvements are needed in the management of patients with endometrial cancer, i.e., the development of non/minimally invasive tools for diagnostics and prognostics, which are currently missing. Diagnostic tools are needed to manage the increasing number of women at risk of developing the disease. Prognostic tools are necessary to stratify patients according to their risk of recurrence pre-preoperatively, to advise and plan the most appropriate treatment and avoid over/under-treatment. Biomarkers derived from proteomics and metabolomics, especially when derived from non/minimally-invasively collected body fluids, can serve to develop such prognostic and diagnostic tools, and the purpose of the present review is to explore the current research in this topic. We first provide a brief description of the technologies, the computational pipelines for data analyses and then we provide a systematic review of all published studies using proteomics and/or metabolomics for diagnostic and prognostic biomarker discovery in endometrial cancer. Finally, conclusions and recommendations for future studies are also given.

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Mass spectrometry‐based high‐throughput proteomics and its role in biomedical studies and systems biology

Cited by 36 publications

References 187 publications

CTSB promotes sepsis-induced acute kidney injury through activating mitochondrial apoptosis pathway

CTSB promotes sepsis-induced acute kidney injury through activating mitochondrial apoptosis pathway

Speedy-PASEF: Analytical flow rate chromatography and trapped ion mobility for deep high-throughput proteomics

Endometrial cancer diagnostic and prognostic algorithms based on proteomics, metabolomics, and clinical data: a systematic review

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