Prospective applications of ultrahigh resolution proteomics in clinical mass spectrometry

Ruhaak, L. Renee; Burgt, Yuri E. M. van der; Cobbaert, Christa

doi:10.1080/14789450.2016.1253477

Cited by 11 publications

(8 citation statements)

References 80 publications

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“…Specifically the introduction of high resolution MS-instruments, which can provide accurate mass information at resolutions >60,000, would be beneficial for the analysis of proteoforms. 186 We believe that in the future, proteoform specific analysis in an extended apo-form panel might provide additional benefits, but such analyses are far from clinical implementation and require further technical development before clinical evaluation could be considered.…”

Section: Conclusion and Future Outlookmentioning

confidence: 99%

Apolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia

2019

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An elevated low-density lipoprotein cholesterol concentration is a classical risk factor for cardiovascular disease. This has led to pharmacotherapy in patients with atherosclerotic heart disease or high heart disease risk with statins to reduce serum low-density lipoprotein cholesterol. Even in patients in whom the target levels of low-density lipoprotein cholesterol are reached, there remains a significant residual cardiovascular risk; this is due, in part, to a focus on low-density lipoprotein cholesterol alone and neglect of other important aspects of lipoprotein metabolism. A more refined lipoprotein analysis will provide additional information on the accumulation of very low-density lipoproteins, intermediate density lipoproteins, chylomicrons, chylomicron-remnants and Lp(a) concentrations. Instead of measuring the cholesterol and triglyceride content of the lipoproteins, measurement of their apolipoproteins (apos) is more informative. Apos are either specific for a particular lipoprotein or for a group of lipoproteins. In particular measurement of apos in atherogenic particles is more biologically meaningful than the measurement of the cholesterol concentration contained in these particles. Applying apo profiling will not only improve characterization of the lipoprotein abnormality, but will also improve definition of therapeutic targets. Apo profiling aligns with the concept of precision medicine by which an individual patient is not treated as ‘average’ patient by the average (dose of) therapy. This concept of precision medicine fits the unmet clinical need for stratified cardiovascular medicine. The requirements for clinical application of proteomics, including apo profiling, can now be met using robust mass spectrometry technology which offers desirable analytical performance and standardization.

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Section: Conclusion and Future Outlookmentioning

confidence: 99%

Apolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia

2019

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“…In OC, biomarker research for early-stage screening has become one of the most exciting uses for MS-based proteomics analysis 23 24 . Clinical specimens including tumors, ascites and serum samples have been assessed for distinct protein/peptide signatures to identify novel proteins which may assist in disease detection 25 . Recently, the methodology has also been used to identify novel therapeutic targets for recurrent diseases based on protein signatures of chemotherapy treated patients 26 .…”

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confidence: 99%

Knockdown of stem cell regulator Oct4A in ovarian cancer reveals cellular reprogramming associated with key regulators of cytoskeleton-extracellular matrix remodelling

Samardzija

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Escalona

et al. 2017

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Oct4A is a master regulator of self-renewal and pluripotency in embryonic stem cells. It is a well-established marker for cancer stem cell (CSC) in malignancies. Recently, using a loss of function studies, we have demonstrated key roles for Oct4A in tumor cell survival, metastasis and chemoresistance in in vitro and in vivo models of ovarian cancer. In an effort to understand the regulatory role of Oct4A in tumor biology, we employed the use of an ovarian cancer shRNA Oct4A knockdown cell line (HEY Oct4A KD) and a global mass spectrometry (MS)-based proteomic analysis to investigate novel biological targets of Oct4A in HEY samples (cell lysates, secretomes and mouse tumor xenografts). Based on significant differential expression, pathway and protein network analyses, and comprehensive literature search we identified key proteins involved with biologically relevant functions of Oct4A in tumor biology. Across all preparations of HEY Oct4A KD samples significant alterations in protein networks associated with cytoskeleton, extracellular matrix (ECM), proliferation, adhesion, metabolism, epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and drug resistance was observed. This comprehensive proteomics study for the first time presents the Oct4A associated proteome and expands our understanding on the biological role of this stem cell regulator in carcinomas.

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“…Some exceptions are the use of ionization sources (e.g., MALDI, SELDI, APCI, PTR, etc.) without a separation step that are directly coupled to the MS (Byrdwell 2001, Petricoin and Liotta 2003, Jordan et al 2009, Gaugg et al 2016, Ruhaak et al 2016). High-performance TOF instruments routinely generate resolutions of 10 000+, and research platforms exceeding 40 000, with very fast cycle times for fragmentations scans.…”

Section: High-resolution Mass Spectrometry: a Brief Historymentioning

confidence: 99%

Beyond monoisotopic accurate mass spectrometry: ancillary techniques for identifying unknown features in non-targeted discovery analysis

2018

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High-resolution mass spectrometry (HR-MS) is an important tool for performing non-targeted analysis for investigating complex organic mixtures in human or environmental media. This perspective demonstrates HR-MS compound identification strategies using atom counting, isotope ratios, and fragmentation pattern analysis based on ‘exact’ or ‘accurate’ mass, which allows analytical distinction among mass fragments with the same integer mass, but with different atomic constituents of the original molecules. Herein, HR-MS technology is shown to narrow down the identity of unknown compounds for specific examples, and ultimately inform future analyses when these compounds reoccur. Although HR-MS is important for all biological media, this is particularly critical for new methods and instrumentation invoking exhaled breath condensate, particles, and aerosols. In contrast to standard breath gas-phase analyses where 1 mass unit (Da) resolution is generally sufficient, the condensed phase breath media are particularly vulnerable to errors in compound identification because the larger organic non-volatile molecules can form identical integer mass fragments from different atomic constituents which then require high-resolution mass analyses to tell them apart.

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Prospective applications of ultrahigh resolution proteomics in clinical mass spectrometry

Cited by 11 publications

References 80 publications

Apolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia

Apolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia

Knockdown of stem cell regulator Oct4A in ovarian cancer reveals cellular reprogramming associated with key regulators of cytoskeleton-extracellular matrix remodelling

Beyond monoisotopic accurate mass spectrometry: ancillary techniques for identifying unknown features in non-targeted discovery analysis

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