The clinical potential of prm-PASEF mass spectrometry

Lesur, Antoine; Dittmar, Gunnar

doi:10.1080/14789450.2021.1908895

Cited by 11 publications

(12 citation statements)

References 39 publications

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“…We calculated a peptide detection ranging from 7.4 (CD99) to 234232 (HEMO) amole injected onto the column for the prm-PASEF. The limit of detection and dynamic range is in line with our previous technical evaluation of the prm-PASEF method on serum and cell extract samples 9,14 . The prm-PASEF detected 27 low abundant peptides below 30 amoles injected whereas the dia-PASEF detected 8 peptides below that threshold.…”

Section: Resultssupporting

confidence: 85%

Highly multiplexed targeted plasma proteomics quantifies several hundred blood proteins in serum from colorectal carcinoma patients

Lesur

Bernardin

Koncina

et al. 2022

Preprint

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The rapid analysis of human serum and plasma can provide deep insights into changes of the blood proteome in response to different patient treatments or diseases. Targeted proteomics techniques, like SRM and PRM, can be utilized to monitor proteins at high sensitivity, but so far were limited to smaller protein panels, which can be monitored in one experiment. The recently, on a Bruker tims-TOF Pro mass spectrometer, developed parallel reaction monitoring-parallel accumulation−serial fragmentation (prm-PASEF) method expands the standard PRM method by using ion-mobility. The use of ion mobility as a fourth separation dimension increases the proteome coverage while reducing the length of the necessary chromatographic separation. By combining an isotope-labeled reference standard, which covers 579 plasma proteins, we were able to quantify 565 proteins in plasma using prm-PASEF, with the least abundant protein being quantified at 7 amol. We continued the analysis by combining the isotope-labeled reference standard with dia-PASEF, which allowed the quantification of 549 proteins. Both methods were used to analyze 20 patient plasma samples from a colorectal cancer (CRC) cohort. The analysis identified 16 differentially regulated proteins between the CRC patient and control individual plasma samples. 15 of the 16 proteins showed a high correlation to the mRNA expression in CRC tumor samples, showing the technique's potential for the rapid identification of potential biomarkers in larger cohorts, abolishing the need for preselection of potential biomarker proteins.

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Section: Resultssupporting

confidence: 85%

Highly multiplexed targeted plasma proteomics quantifies several hundred blood proteins in serum from colorectal carcinoma patients

Lesur

Bernardin

Koncina

et al. 2022

Preprint

Self Cite

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“…28 Also, prm-PASEF, as an alternative of SRM/MRM/PRM, can take advantage of a dual ion mobility trap, enabling highly multiplexed targeted acquisition and thus requiring a shorter chromatographic separation without sacrificing the number of targeted peptides, as mentioned by Lesur and Dittmar. 24 ■ ASSOCIATED CONTENT * sı Supporting Information…”

Section: ■ Conclusionmentioning

confidence: 99%

“…The timsTOF Pro instrument used for this study has a newly developed prm-PASEF option. 24 A new approach"4D proteomics"was utilized. Four characteristics (retention time (RT), ion mobility (IM), precursor m/z (MS), and the corresponding fragment ions (MS/MS)) were measured for each peptide and used for the prm-PASEF method development (Figure 1).…”

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confidence: 99%

The Parallel Reaction Monitoring-Parallel Accumulation–Serial Fragmentation (prm-PASEF) Approach for Multiplexed Absolute Quantitation of Proteins in Human Plasma

et al. 2022

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Mass spectrometry (MS)-based quantitative proteomic methods have become some of the major tools for protein biomarker discovery and validation. The recently developed parallel reaction monitoring-parallel accumulation−serial fragmentation (prm-PASEF) approach on a Bruker timsTOF Pro mass spectrometer allows the addition of ion mobility as a new dimension to LC-MS-based proteomics and increases proteome coverage at a reduced analysis time. In this study, a prm-PASEF approach was used for the multiplexed absolute quantitation of proteins in human plasma using isotope-labeled peptide standards for 125 plasma proteins, over a broad (10 4 −10 6 ) dynamic range. Optimization of LC and MS parameters, such as accumulation time and collision energy, resulted in improved sensitivity for more than half of the targets (73 out of 125 peptides) by increasing the signal-tonoise ratio by a factor of up to 10. Overall, 41 peptides showed up to a 2-fold increase in sensitivity, 25 peptides showed up to a 5fold increase in sensitivity, and 7 peptides showed up to a 10-fold increase in sensitivity. Implementation of the prm-PASEF method allowed absolute protein quantitation (down to 1.13 fmol) in human plasma samples. A comparison of the concentration values of plasma proteins determined by MRM on a QTRAP instrument and by prm-PASEF on a timsTOF Pro revealed an excellent correlation (R 2 = 0.97) with a slope of close to 1 (0.99), demonstrating that prm-PASEF is well suited for "absolute" quantitative proteomics.

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“…Improved instrumentation, including faster scan speeds, parallel accumulation serial fragmentation (PASEF) [ 22 , 23 ], and trapped ion mobility [ 24 , 25 ], enables the identification of disease-associated proteins and their modifications from patient samples using small sample volumes. While these technological advances drive the limits of quantitation and enable sensitive analysis to gain the greatest depth in proteome being measured, the need to analyze thousands of samples robustly still remains a challenge in biomarker discovery.…”

Section: Overview Of Proteomics Technological Advancement For Biomark...mentioning

confidence: 99%

Biomarkers in Neurodegenerative Diseases: Proteomics Spotlight on ALS and Parkinson’s Disease

Raghunathan

Turajane

Wong

2022

IJMS

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Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) are both characterized by pathogenic protein aggregates that correlate with the progressive degeneration of neurons and the loss of behavioral functions. Both diseases lack biomarkers for diagnosis and treatment efficacy. Proteomics is an unbiased quantitative tool capable of the high throughput quantitation of thousands of proteins from minimal sample volumes. We review recent proteomic studies in human tissues, plasma, cerebrospinal fluid (CSF), and exosomes in ALS and PD that identify proteins with potential utility as biomarkers. Further, we review disease-related post-translational modifications in key proteins TDP43 in ALS and α-synuclein in PD studies, which may serve as biomarkers. We compare relative and absolute quantitative proteomic approaches in key biomarker studies in ALS and PD and discuss recent technological advancements which may identify suitable biomarkers for the early-diagnosis treatment efficacy of these diseases.

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The clinical potential of prm-PASEF mass spectrometry

Cited by 11 publications

References 39 publications

Highly multiplexed targeted plasma proteomics quantifies several hundred blood proteins in serum from colorectal carcinoma patients

Highly multiplexed targeted plasma proteomics quantifies several hundred blood proteins in serum from colorectal carcinoma patients

The Parallel Reaction Monitoring-Parallel Accumulation–Serial Fragmentation (prm-PASEF) Approach for Multiplexed Absolute Quantitation of Proteins in Human Plasma

Biomarkers in Neurodegenerative Diseases: Proteomics Spotlight on ALS and Parkinson’s Disease

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