The Analyst, Год журнала: 2024, Номер 150(2), С. 353 - 361
Опубликована: Дек. 13, 2024
Absolute LC/MRM-MS based quantitation targeting 270 proteins yielded 44% more quantifiable when combined with automated nanoparticle (NP)-based fractionation and digestion approach as compared to neat trypsin digestion.
Язык: Английский
Molecular & Cellular Proteomics, Год журнала: 2024, Номер 23(5), С. 100760 - 100760
Опубликована: Апрель 3, 2024
We describe deep analysis of the human proteome in less than one hour. achieve this expedited characterization by leveraging state-of-the-art sample preparation, chromatographic separations, data tools, and using new Orbitrap Astral mass spectrometer equipped with a quadrupole filter, high-field analyzer, an asymmetric track lossless (Astral) analyzer. The system offers high MS/MS acquisition speed 200 Hz detects hundreds peptide sequences per second within independent- or data-dependent modes operation. fast-switching capabilities complement sensitivity fast ion scanning analyzer to enable narrow-bin data-independent (DIA) methods. Over 30-minute active method consuming total time 56 minutes, Q-Orbitrap-Astral hybrid MS collects average 4,319 MS1 scans 438,062 run, producing 235,916 (1% false discovery rate (FDR)). On average, each achieved detection 10,411 protein groups FDR). conclude, these results alongside other recent reports, that one-hour is reach.
Язык: Английский
Процитировано
22
Nature Genetics, Год журнала: 2025, Номер unknown
Опубликована: Фев. 19, 2025
Abstract Our current understanding of the determinants plasma proteome variation during pediatric development remains incomplete. Here, we show that genetic variants, age, sex and body mass index significantly influence this variation. Using a streamlined highly quantitative spectrometry-based proteomics workflow, analyzed from 2,147 children adolescents, identifying 1,216 proteins after quality control. Notably, levels 70% these were associated with at least one aforementioned factors, protein also being predictive. Quantitative trait loci (QTLs) regulated one-third proteins; between few percent up to 30-fold. Together excellent replication in an additional 1,000 558 adults, reveals substantial effects on levels, persisting childhood into adulthood. Through Mendelian randomization colocalization analyses, identified 41 causal genes for 33 cardiometabolic traits, emphasizing value QTLs drug target identification disease understanding.
Язык: Английский
Процитировано
2
Molecular & Cellular Proteomics, Год журнала: 2024, Номер 23(7), С. 100786 - 100786
Опубликована: Май 17, 2024
Язык: Английский
Процитировано
12
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июнь 1, 2024
Genome-wide association studies (GWAS) with proteomics are essential tools for drug discovery. To date, most have used affinity platforms, which limited discovery to protein panels covered by the available binders. Furthermore, it is not clear extent epitope changing variants interfere detection of quantitative trait loci (pQTLs). Mass spectrometry-based (MS) can overcome some these limitations. Here we report a GWAS using MS-based Seer Proteograph
Язык: Английский
Процитировано
10
Biomolecules, Год журнала: 2025, Номер 15(1), С. 130 - 130
Опубликована: Янв. 15, 2025
Proteomics accelerates diagnosis and research of muscular diseases by enabling the robust analysis proteins relevant for manifestation neuromuscular in following aspects: (i) evaluation effect genetic variants on corresponding protein, (ii) prediction underlying defect based proteomic signature muscle biopsies, (iii) pathophysiologies different entities diseases, key definition new intervention concepts, (iv) patient stratification according to biochemical fingerprints as well (v) monitoring success therapeutic interventions. This review presents—also through exemplary case studies—the various advantages mass proteomics investigation discusses technical limitations, provides an outlook possible future application concepts. Hence, is excellent large-scale analytical tool diagnostic workup (hereditary) warrants systematic profiling pathophysiological processes. The steady development may allow overcome existing limitations including a quenched dynamic range quantification protein isoforms. Future directions include targeted settings using not only biopsies but also liquid address need minimally invasive procedures.
Язык: Английский
Процитировано
1
Molecular & Cellular Proteomics, Год журнала: 2024, Номер 23(9), С. 100830 - 100830
Опубликована: Авг. 14, 2024
The study of the cellular secretome using proteomic techniques continues to capture attention research community across a broad range topics in biomedical research. Due their untargeted nature, independence from model system used, historically superior depth analysis, as well comparative affordability, mass spectrometry-based approaches traditionally dominate such analyses. More recently, however, affinity-based assays have massively gained analytical depth, which together with high sensitivity, dynamic coverage throughput capabilities render them exquisitely suited analysis. In this review, we revisit challenges implied by secretomics and provide an overview platforms currently available for analyses, tumor example basic translational
Язык: Английский
Процитировано
6
Nature Reviews Bioengineering, Год журнала: 2024, Номер 2(10), С. 887 - 905
Опубликована: Июль 8, 2024
Язык: Английский
Процитировано
5
Journal of Proteome Research, Год журнала: 2024, Номер unknown
Опубликована: Окт. 31, 2024
Recent improvements in proteomics technologies have fundamentally altered our capacities to characterize human biology. There is an ever-growing interest using these novel methods for studying the circulating proteome, as blood offers accessible window into health. However, every methodological innovation and analytical progress calls reassessing existing approaches routines ensure that new data will add value greater biomedical research community avoid previous errors. As representatives of HUPO's Human Plasma Proteome Project (HPPP), we present 2024 survey current community, including latest build PeptideAtlas now comprises 4608 proteins detected 113 sets. We then discuss updates established methods, emerging technologies, investigations proteoforms, protein networks, extracellualr vesicles, antibodies microsamples. Finally, provide a prospective view tools studies proteins.
Язык: Английский
Процитировано
4
medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Янв. 13, 2025
Abstract We report a systematic quantification of 10,841 unique proteins from over 700 GTEx samples, representing five human tissues. Sex, age and genetic factors are associated with variation in protein abundance. In total, 1981 cis-protein quantitative trait loci (cis-pQTL) identified, which majority targets have not been assayed the recent plasma-based proteogenomic studies. Integrating transcriptomic information matching tissues delineates concordant as well discordant expression patterns at RNA levels. Juxtaposition data different indicates both shared tissue-specific architecture that underlie Complementing genomic annotation, RNA-based eQTL studies, establishment characterization, tissue-pQTLs shed light on biology underlying genotype-phenotype association complex traits diseases.
Язык: Английский
Процитировано
0
Cell Genomics, Год журнала: 2025, Номер unknown, С. 100763 - 100763
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0