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- Kawahara, R., et al.
(författare)
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Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis
- 2021
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 18, s. 1304-1316
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Tidskriftsartikel (refereegranskat)abstract
- Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. This analysis presents the results of a community-based evaluation of existing software for large-scale glycopeptide data analysis.
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- Ramirez, M. I., et al.
(författare)
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Technical challenges of working with extracellular vesicles
- 2018
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 10:3, s. 881-906
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review. © 2018 The Royal Society of Chemistry.
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- Ally, M., et al.
(författare)
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Cross-sectional and longitudinal evaluation of plasma glial fibrillary acidic protein to detect and predict clinical syndromes of Alzheimer's disease
- 2023
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This study examined plasma glial fibrillary acidic protein (GFAP) as a biomarker of cognitive impairment due to Alzheimer's disease (AD) with and against plasma neurofilament light chain (NfL), and phosphorylated tau (p-tau)181+231.Methods: Plasma samples were analyzed using Simoa platform for 567 participants spanning the AD continuum. Cognitive diagnosis, neuropsychological testing, and dementia severity were examined for cross-sectional and longitudinal outcomes.Results: Plasma GFAP discriminated AD dementia from normal cognition (adjusted mean difference = 0.90 standard deviation [SD]) and mild cognitive impairment (adjusted mean difference = 0.72 SD), and demonstrated superior discrimination compared to alternative plasma biomarkers. Higher GFAP was associated with worse dementia severity and worse performance on 11 of 12 neuropsychological tests. Longitudinally, GFAP predicted decline in memory, but did not predict conversion to mild cognitive impairment or dementia.Discussion: Plasma GFAP was associated with clinical outcomes related to suspected AD and could be of assistance in a plasma biomarker panel to detect in vivo AD.
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- Chatterjee, S., et al.
(författare)
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Protein Paucimannosylation Is an Enriched N-Glycosylation Signature of Human Cancers
- 2019
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 19:21-22
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Tidskriftsartikel (refereegranskat)abstract
- While aberrant protein glycosylation is a recognized characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumorigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and cancer. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens are profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade. PMGs, particularly Man2‐3GlcNAc2Fuc1, are prominent features of 29 cancer cell lines, but the PMG level varies dramatically across and within the cancer types (1.0–50.2%). Analyses of paired (tumor/non‐tumor) and stage‐stratified tissues demonstrate that PMGs are significantly enriched in tumor tissues from several cancer types including liver cancer (p = 0.0033) and colorectal cancer (p = 0.0017) and is elevated as a result of prostate cancer and chronic lymphocytic leukaemia progression (p < 0.05). Surface expression of paucimannosidic epitopes is demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase is indicated by quantitative proteomics. This intriguing association between protein paucimannosylation and human cancers warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers, and functions of paucimannosylation in tumorigenesis and metastasis.
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- Lambert-Niclot, S., et al.
(författare)
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Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: Raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART
- 2016
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 71:4, s. 1056-1062
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). Methods: Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and for RT, protease and integrase (IN) genes for patients with a confirmed viral load (VL) >50 copies/mL or any single VL >500 copies/mL during or after week 32. Results: A resistance test was obtained for 110/805 (13.7%) randomized participants qualifying for resistance analysis (61/401 of participants in the raltegravir arm and 49/404 of participants in the tenofovir/emtricitabine arm). No resistance-associated mutation (RAM) was observed in the tenofovir/emtricitabine plus darunavir/ritonavir arm, and all further analyses were limited to the raltegravir plus darunavir arm. In this group, 15/55 (27.3%) participants had viruses with IN RAMs (12 N155H alone, 1 N155H + Q148R, 1 F121Y and 1 Y143C), 2/53 (3.8%) with nucleotide analogue RT inhibitor RAMs (K65R, M41L) and 1/57 (1.8%) with primary protease RAM (L76V). The frequency of IN mutations at failure was significantly associated with baseline VL: 7.1% for a VL of TREND = 0.007). Of note, 4/15 participants with IN RAM had a VL <200 copies/mL at time of testing. Conclusions: In the NEAT001/ANRS143 trial, there was no RAM at virological failure in the standard tenofovir/emtricitabine plus darunavir/ritonavir regimen, contrasting with a rate of 29.5% (mostly IN mutations) in the raltegravir plus darunavir/ritonavir NRTI-sparing regimen. The cumulative risk of IN RAM after 96 weeks of follow-up in participants initiating ART with raltegravir plus darunavir/ritonavir was 3.9%.
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| 8. |
- Morrison, M. S., et al.
(författare)
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Ante-mortem plasma phosphorylated tau (181) predicts Alzheimer's disease neuropathology and regional tau at autopsy
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:10, s. 3546-3557
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Tidskriftsartikel (refereegranskat)abstract
- In one of the largest studies of its kind, Morrison et al. show that ante-mortem plasma phosphorylated-tau(181) concentrations accurately differentiate brain donors with and without autopsy-confirmed Alzheimer's disease. Blood tests could be a minimally invasive, cost-effective tool for the detection and monitoring of Alzheimer's disease. Blood-based biomarkers such as tau phosphorylated at threonine 181 (phosphorylated-tau(181)) represent an accessible, cost-effective and scalable approach for the in vivo detection of Alzheimer's disease pathophysiology. Plasma-pathological correlation studies are needed to validate plasma phosphorylated-tau(181) as an accurate and reliable biomarker of Alzheimer's disease neuropathological changes. This plasma-to-autopsy correlation study included participants from the Boston University Alzheimer's Disease Research Center who had a plasma sample analysed for phosphorylated-tau(181) between 2008 and 2018 and donated their brain for neuropathological examination. Plasma phosphorelated-tau(181) was measured with single molecule array technology. Of 103 participants, 62 (60.2%) had autopsy-confirmed Alzheimer's disease. Average time between blood draw and death was 5.6 years (standard deviation = 3.1 years). Multivariable analyses showed higher plasma phosphorylated-tau(181) concentrations were associated with increased odds for having autopsy-confirmed Alzheimer's disease [AUC = 0.82, OR = 1.07, 95% CI = 1.03-1.11, P < 0.01; phosphorylated-tau standardized (z-transformed): OR = 2.98, 95% CI = 1.50-5.93, P < 0.01]. Higher plasma phosphorylated-tau(181) levels were associated with increased odds for having a higher Braak stage (OR = 1.06, 95% CI = 1.02-1.09, P < 0.01) and more severe phosphorylated-tau across six cortical and subcortical brain regions (ORs = 1.03-1.06, P < 0.05). The association between plasma phosphorylated-tau(181) and Alzheimer's disease was strongest in those who were demented at time of blood draw (OR = 1.25, 95%CI = 1.02-1.53), but an effect existed among the non-demented (OR = 1.05, 95% CI = 1.01-1.10). There was higher discrimination accuracy for Alzheimer's disease when blood draw occurred in years closer to death; however, higher plasma phosphorylated-tau(181) levels were associated with Alzheimer's disease even when blood draw occurred >5 years from death. Ante-mortem plasma phosphorylated-tau(181) concentrations were associated with Alzheimer's disease neuropathology and accurately differentiated brain donors with and without autopsy-confirmed Alzheimer's disease. These findings support plasma phosphorylated-tau(181) as a scalable biomarker for the detection of Alzheimer's disease.
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| 10. |
- Fisher, James L., et al.
(författare)
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Loud Noise Exposure and Acoustic Neuroma
- 2014
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 180:1, s. 58-67
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Tidskriftsartikel (refereegranskat)abstract
- The results from studies of loud noise exposure and acoustic neuroma are conflicting. A population-based case-control study of 451 acoustic neuroma patients and 710 age-, sex-, and region-matched controls was conducted in Sweden between 2002 and 2007. Occupational exposure was based on historical measurements of occupational noise (321 job titles summarized by a job exposure matrix) and compared with self-reported occupational noise exposure. We also evaluated self-reported noise exposure during leisure activity. Conditional logistic regression was used to estimate odds ratios. There was no statistically significant association between acoustic neuroma and persistent occupational noise exposure, either with or without hearing protection. Exposure to loud noise from leisure activity without hearing protection was more common among acoustic neuroma cases (odds ratio = 1.47, 95% confidence interval: 1.06, 2.03). Statistically significant odds ratios were found for specific leisure activities including attending concerts/clubs/sporting events (odds ratio = 1.82, 95% confidence interval: 1.09, 3.04) and participating in workouts accompanied by loud music (odds ratio = 2.84, 95% confidence interval: 1.37, 5.89). Our findings do not support an association between occupational exposure to loud noise and acoustic neuroma. Although we report statistically significant associations between leisure-time exposures to loud noise without hearing protection and acoustic neuroma, especially among women, we cannot rule out recall bias as an alternative explanation.
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