Mass spectrometry-based proteomics as an emerging tool in clinical laboratories

Clinical Proteomics, Journal Year: 2023, Volume and Issue: 20(1)

Published: Aug. 26, 2023

Abstract Mass spectrometry (MS)-based proteomics have been increasingly implemented in various disciplines of laboratory medicine to identify and quantify biomolecules a variety biological specimens. MS-based is continuously expanding widely applied biomarker discovery for early detection, prognosis markers treatment response prediction monitoring. Furthermore, making these advanced tests more accessible affordable will the greatest healthcare benefit. This review article highlights new paradigms clinical has created microbiology laboratories, cancer research diagnosis metabolic disorders. The technique preferred over conventional methods disease detection therapy monitoring its combined advantages multiplexing capacity, remarkable analytical specificity sensitivity low turnaround time. Despite achievements development adoption number practices, are expected undergo transition from bench bedside near future. provides insights trials recent progresses (mainly covering literature NCBI database) application laboratories.

Language: Английский

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Data-Independent Acquisition: A Milestone and Prospect in Clinical Mass Spectrometry–Based Proteomics

Molecular & Cellular Proteomics, Journal Year: 2024, Volume and Issue: 23(8), P. 100800 - 100800

Published: June 15, 2024

Language: Английский

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Nanoparticles overcome adaptive immune resistance and enhance immunotherapy via targeting tumor microenvironment in lung cancer

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 24, 2023

Lung cancer is one of the common malignant cancers worldwide. Immune checkpoint inhibitor (ICI) therapy has improved survival lung patients. However, ICI leads to adaptive immune resistance and displays PD-1/PD-L1 blockade in cancer, leading less response Tumor microenvironment (TME) an integral tumor microenvironment, which involved immunotherapy resistance. Nanomedicine been used enhance cancer. In this review article, we described association between TME We also highlighted importance Moreover, discussed how nanoparticles are regulation improve efficacy immunotherapy, including SGT-53, AZD1080, Nanomodulator NRF2, Cisplatin nanoparticles, Au@PG, DPAICP@ME, SPIO NP@M-P, NBTXR3 ARAC Nano-DOX, MS NPs, Nab-paclitaxel, GNPs-hPD-L1 siRNA. Furthermore, concluded that targeting by could be helpful overcome

Language: Английский

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High-Throughput Proteomics and Phosphoproteomics of Rat Tissues Using Microflow Zeno SWATH

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(7), P. 2355 - 2366

Published: May 31, 2024

High-throughput tissue proteomics has great potential in the advancement of precision medicine. Here, we investigated combined sensitivity trap-elute microflow liquid chromatography with a ZenoTOF for DIA and phosphoproteomics. Method optimization was conducted on HEK293T cell lines to determine optimal variable window size, MS2 accumulation time gradient length. The 7600 then compared previous generation TripleTOF 6600 using eight rat organs, finding up 23% more proteins fifth sample load third instrument time. Spectral reference libraries generated from Zeno SWATH data FragPipe (MSFragger-DIA/DIA-NN) contained 4 times fragment ions than DIA-NN only library quantified proteins. Replicate single-shot phosphopeptide enrichments 50–100 μg tryptic peptide were analyzed by HPLC without fractionation. Using Spectronaut shallow phosphoproteome containing 1000–3000 phosphoprecursors per organ. Promisingly, clear hierarchical clustering organs observed high Pearson correlation coefficients >0.95 between replicate median CV 20%. allows high-throughput quantitation an extensive proteome small samples.

Language: Английский

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Proteomic Characterization of Acute Myeloid Leukemia for Precision Medicine

Molecular & Cellular Proteomics, Journal Year: 2023, Volume and Issue: 22(4), P. 100517 - 100517

Published: Feb. 18, 2023

Acute myeloid leukemia (AML) is a highly heterogeneous cancer of the hematopoietic system with no cure for most patients. In addition to chemotherapy, treatment options AML include recently approved therapies that target proteins roles in pathobiology, such as FLT3, BLC2, and IDH1/2. However, due disease complexity, these produce very diverse responses, survival rates are still low. Thus, despite considerable advances, there remains need different aspects leukemic biology associated biomarkers define patient populations likely respond each available therapy. To meet this need, drugs vulnerabilities currently advanced stages clinical development. Here, we review proteomics phosphoproteomics studies aimed provide insights into heterogeneity not attainable genomic approaches. place discussion context, first an overview genetic disease, followed by summary targeted compounds have been or under trials and, if available, predict responses. We then discuss provided pathogenesis, from which potential drug targets were identified, rationalize use synergistic combinations. When considered whole, evidence summarized here suggests approaches can play crucial role development implementation precision medicine

Language: Английский

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Metabolomics in oncology

Cancer Reports, Journal Year: 2023, Volume and Issue: 6(3)

Published: Feb. 21, 2023

Abstract Background Oncogenic transformation alters intracellular metabolism and contributes to the growth of malignant cells. Metabolomics, or study small molecules, can reveal insight about cancer progression that other biomarker studies cannot. Number metabolites involved in this process have been spotlight for detection, monitoring, therapy. Recent Findings In review, “Metabolomics” is defined terms current technology having both clinical translational applications. Researchers shown metabolomics be used discern metabolic indicators non‐invasively using different analytical methods like positron emission tomography, magnetic resonance spectroscopic imaging etc. Metabolomic profiling a powerful technically feasible way track changes tumor gauge treatment response across time. also predict individual treatment, measure medication efficacy, monitor drug resistance. Its significance development summarized review. Conclusion Although infancy, identify options and/or responsiveness treatments. Technical challenges database management, cost methodical knowhow still persist. Overcoming these near further help designing new régimes with increased sensitivity specificity.

Language: Английский

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Unlocking Early Cancer Detection: Exploring Biomarkers, Circulating DNA, and Innovative Technological Approaches

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 25, 2023

Research and development improvements in early cancer diagnosis have had a significant positive impact on health. In the treatment prevention of cancer, detection is essential. this context, biomarkers are essential because they offer important information state cells at any particular time. Cells go through unique changes when shift from healthy condition to malignant state, that appropriate may pick up. Recent advancements been made identify characterize circulating cancer-specific mutations cell-free DNA derived tumors tumor cells. A patient's delay between time first detect symptoms contact doctor has noted for many forms. The tumor's location features significantly presentation judged diagnosis. Lack knowledge severity be one cause delay. Our review largely focused ongoing developments study biomarkers, diagnosis, biology challenges, symptoms, liquid biopsies, detectable by imaging, established markers, plasma technologies, gender differences, artificial intelligence (AI) This aims determine evaluate Indicators detecting assessing medical conditions, evaluating potential risks. For Individuals with heightened likelihood developing or who already diagnosed, identification crucial enhancing prognosis raising effective treatment.

Language: Английский

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Recent advances of data‐independent acquisition mass spectrometry‐based proteomics

PROTEOMICS, Journal Year: 2023, Volume and Issue: 23(7-8)

Published: April 1, 2023

Bottom-up proteomics is a mass spectrometry-based method to analyze the contents of complex protein samples. Pioneered in 1990s, it consists converting samples into peptide by enzymatic digestion, separation peptides (typically) reverse phase liquid chromatography (LC), and analysis eluting tandem spectrometry. This general approach, while tremendously successful widely used, has faced from beginning fundamental challenge that number generated digestion sample, like cell extracts or body fluids, significantly larger than expected application tryptic rule [1]. In fact, proteome presently unknown. Ironically, genes transcripts could be comprehensively sequenced characterized, exact types their cellular copy any biomedical sample remains The address this issue spawned large strategies for spectrometric data acquisition analysis. Two major bottom-up approaches have been developed. Data-dependent (DDA) essentially prioritizes precursors based on signal intensity precursor ion scan spectrometer, then subsequentially selects fragmentation, generating MS2 spectra. well-established MS method, which gains throughput when coupled with stable isotope-labeling using, example, TMTpro. However, since substantially fragment spectra spectrometer can acquire, only limited analyzed, leaving out varying unknown portion uncharacterized each DDA acquisition. undersampling becomes more pronounced LC gradient minimized maximize throughput. Therefore, unlikely acquisition, even extensive fractionation extremely long gradient, will overcome issue. Another emerging adopted approach data-independent (DIA). DIA bins predefined groups m/z values, performs fragmentation group (also called "window") sequentially, records highly convoluted spectrum fragments unfragmented window [2]. generates comprehensive digital map all flyable fragmentable proteome. compared inherently issue, theoretically possible identify every DIA. Various computational methods developed acquired They grouped conceptually peptide-centric spectrum-centric approaches, terminology MacCoss colleagues [3]. With interpreted searching against theoretical experimental sequence database matched decoy database. usually used data. Principally, also applied data, but most effectively basically asks question: interest present data? Briefly, first compiles characteristics (including fragments, retention time elution profiles, among others) table (eg. reference spectral library), tries find pattern using statistical machine learning algorithms [4]. principle, combination strategy allows analyzable within limits analytical techniques used. Since 2010, over 1000 publications published special features some latest advances field. Penny et al. reported gas scheme (ion mobility) IM - (gas fractionation) GPF, rapid diaPASEF library generation [5]. Most analyses are performed single injections elimination not minimizes technical variability required amount, increases Bons study small amounts extracellular matrix lung cancer tissue specimens [6], Wang analyzed enriched glycoproteins urine prostate patients [7]. Kverneland simple ultracentrifugation protocol enrichment vesicles plasma samples, enabling characterization 2500 proteins runs less 1 h [8]. These three applications exemplify superb sensitivity comprehensiveness DIA-MS analyzing specific subproteome. Oliinyk dia-PASEF characterized 13,000 phosphopeptides about 20 ug digests, shortening factor 4 led similar coverage phosphoproteome [9]. type requires both high currently practical DIA-MS. Messner argued perturbation an essential dynamic biological systems short-gradient fast choice such [10]. addition, acquires ions, unique advantages PTMs. Yang reviewed current status DIA-based PTM detection, site localization, glycans [11]. particular, they contribution deep interpretation. Pham algorithm transformer architecture prediction exhibited performance multiple existing software tools [12]. effective clinical high-throughput degree reproducibility cohorts [13]. Encouraged recent proteomics, Boys ProCan asked where we context (large-scale) MS-based proteomics? Even though disease diagnostic biomarkers potential therapeutic targets, as yet implemented routine diagnostics. discussed hurdles proposed actions move forward including integration multiomics measurements, development targeted proteomic assays [14]. Poulos al., too, different angle, drug discovery [15]. High-throughput tumor cells. resultant potentially responsiveness learning. Although seen wide discovery, clear indisputable. Toward standardization preparation, storage, well essential. Indeed, although volume accumulating, discussion management largely lags behind. Here, Jones [16] findability, accessibility, interoperability, reusability (FAIR) increasing expert recommendations future. Several exciting research fields driven included actively advancing, single-cell spatial proteogenomics.

Language: Английский

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An Inflection Point in Cancer Protein Biomarkers: What was and What's Next

Molecular & Cellular Proteomics, Journal Year: 2023, Volume and Issue: 22(7), P. 100569 - 100569

Published: May 16, 2023

Biomarkers remain the highest value proposition in cancer medicine today-especially protein biomarkers. Despite decades of evolving regulatory frameworks to facilitate review emerging technologies, biomarkers have been mostly about promise with very little show for improvements human health. Cancer is an emergent property a complex system, and deconvoluting integrative dynamic nature overall system through daunting proposition. The last 2 seen explosion multiomics profiling range advanced technologies precision medicine, including emergence liquid biopsy, exciting advances single-cell analysis, artificial intelligence (machine deep learning) data many other that transform biomarker discovery. Combining multiple omics modalities acquire more comprehensive landscape disease state, we are increasingly developing support therapy selection patient monitoring. Furthering especially oncology, necessitates moving away from lens reductionist thinking toward viewing understanding diseases are, fact, adaptive systems. As such, believe it necessary redefine as representations biological states at different hierarchical levels order. This definition could include traditional molecular, histologic, radiographic, or physiological characteristics, well classes digital markers algorithms. To succeed future, must move past purely observational individual studies instead start building mechanistic framework enable analysis new within context prior studies. Identifying information systems applying theoretical constructs, such theory, study dysregulated communication prove be "game changing" clinical outcome patients.

Language: Английский

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High‐throughput molecular assays for inclusion in personalised oncology trials – State‐of‐the‐art and beyond

Journal of Internal Medicine, Journal Year: 2024, Volume and Issue: 295(6), P. 785 - 803

Published: May 2, 2024

Abstract In the last decades, development of high‐throughput molecular assays has revolutionised cancer diagnostics, paving way for concept personalised medicine. This progress been driven by introduction such technologies through biomarker‐driven oncology trials. this review, strengths and limitations various state‐of‐the‐art sequencing technologies, including gene panel (DNA RNA), whole‐exome/whole‐genome whole‐transcriptome sequencing, are explored, focusing on their ability to identify clinically relevant biomarkers with diagnostic, prognostic and/or predictive impact. includes need assess complex biomarkers, example microsatellite instability, tumour mutation burden homologous recombination deficiency, patients suitable specific therapies, immunotherapy. Furthermore, crucial role biomarker analysis multidisciplinary boards in selecting trial inclusion is discussed relation concepts, drug repurposing. Recognising that today's exploratory techniques will evolve into tomorrow's routine diagnostics clinical study assays, importance emerging multimodal as proteomics vivo sensitivity testing, also discussed. addition, key regulatory aspects patient engagement all phases a described. Finally, we propose set recommendations consideration when planning new precision medicine trial.

Language: Английский

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