CE-MS analysis of the human urinary proteome for biomarker discovery and disease diagnostics

Urine is a very good source for biomarker discovery because it accumulates changes in the body. However, a major challenge in urinary biomarker discovery is the fact that the urinary proteome is influenced by various elements. To circumvent these problems, simpler systems, such as animal models, can be used to establish associations between physiological or pathological conditions and alterations in the urinary proteome. In this study, the urinary proteomes of young (two months old) and old rats (20 months old; nine in each group) were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between the young and old rats. Based on criteria of a fold change ≥2,P< 0.05 and identification in each rat of the high-abundance group, 33 proteins were found to be changed (15 increased and 18 decreased in old rats). By adding a more stringent standard (protein spectral counts from every rat in the higher group greater than those in the lower group), eight proteins showed consistent changes in all rats of the groups; two of these proteins are also altered in the urinary proteome of aging humans. However, no shared proteins between our results and the previous aging plasma proteome were identified. Twenty of the 33 (60%) altered proteins have been reported to be disease biomarkers, suggesting that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs which, according to the Human Protein Atlas, are strongly expressed in the kidney, intestine, cerebellum and lung. Therefore, the urinary proteome may reflect aging conditions in these organs.

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The potential urinary aging markers of 20-month-old rats

10.7287/peerj.preprints.1494 ◽

2015 ◽

Cited By ~ 1

Author(s):

Youhe Gao ◽

Xundou Li

Keyword(s):

Biomarker Discovery ◽

Disease Biomarkers ◽

Urinary Proteome ◽

Pathological Conditions ◽

Human Orthologs ◽

Human Protein Atlas ◽

Aging Conditions ◽

Old Rats ◽

Spectral Counts ◽

Standard Protein

Urine is a very good source for biomarker discovery because it accumulates the changes of body. The urinary proteome is influenced by various factors, which is a major challenge in urinary biomarker discovery. To circumvent these problems, simpler systems, such as animal models, should be used to establish associations between physiological or pathological conditions and changes in the urinary proteome. In this study, the urinary proteome of young (2-month-old) and old rats (20-month-old; 9 in each group) were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between young and old rats. Based on the criteria of a fold change ≥ 2, P < 0.05 and being identified in each rat in the high abundance group, 33 proteins were changed (15 up-regulated and 18 down-regulated in old rats). By adding a more stringent standard (protein spectral counts from every rat in the higher group greater than those in the lower group), 8 proteins were changed consistently in all rats of between the groups, 2 of which are also altered in the urinary proteome of aging humans. There are no shared proteins between our results and the previous aging plasma proteome. Twenty of the 33 (60 %) changed proteins have been reported to be disease biomarkers, which implies that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs, which are strongly expressed in the kidney, intestine, cerebellum and lung, according to the human protein ATLAS. Therefore, the urinary proteome may reflect aging conditions in these organs.

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The potential urinary aging markers of 20-month-old rats

10.7287/peerj.preprints.1494v2 ◽

2015 ◽

Author(s):

Youhe Gao ◽

Xundou Li

Keyword(s):

Biomarker Discovery ◽

Disease Biomarkers ◽

Urinary Proteome ◽

Pathological Conditions ◽

Human Orthologs ◽

Human Protein Atlas ◽

Aging Conditions ◽

Old Rats ◽

Spectral Counts ◽

Standard Protein

Urine is a very good source for biomarker discovery because it accumulates the changes of body. The urinary proteome is influenced by various factors, which is a major challenge in urinary biomarker discovery. To circumvent these problems, simpler systems, such as animal models, should be used to establish associations between physiological or pathological conditions and changes in the urinary proteome. In this study, the urinary proteome of young (2-month-old) and old rats (20-month-old; 9 in each group) were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between young and old rats. Based on the criteria of a fold change ≥ 2, P < 0.05 and being identified in each rat in the high abundance group, 33 proteins were changed (15 up-regulated and 18 down-regulated in old rats). By adding a more stringent standard (protein spectral counts from every rat in the higher group greater than those in the lower group), 8 proteins were changed consistently in all rats of between the groups, 2 of which are also altered in the urinary proteome of aging humans. There are no shared proteins between our results and the previous aging plasma proteome. Twenty of the 33 (60 %) changed proteins have been reported to be disease biomarkers, which implies that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs, which are strongly expressed in the kidney, intestine, cerebellum and lung, according to the human protein ATLAS. Therefore, the urinary proteome may reflect aging conditions in these organs.

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Advances in urinary proteome analysis and biomarker discovery in pediatric renal disease

Pediatric Nephrology ◽

10.1007/s00467-009-1251-5 ◽

2010 ◽

Vol 25 (1) ◽

pp. 27-35 ◽

Cited By ~ 55

Author(s):

Cécile Caubet ◽

Chrystelle Lacroix ◽

Stéphane Decramer ◽

Jens Drube ◽

Jochen H. H. Ehrich ◽

...

Keyword(s):

Renal Disease ◽

Biomarker Discovery ◽

Proteome Analysis ◽

Urinary Proteome

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The potential urinary aging markers of 20-month-old rats

10.7287/peerj.preprints.1494v1 ◽

2015 ◽

Author(s):

Youhe Xundou Gao ◽

Xundou Xundou Li

Keyword(s):

Biomarker Discovery ◽

Disease Biomarkers ◽

Urinary Proteome ◽

Pathological Conditions ◽

Human Orthologs ◽

Human Protein Atlas ◽

Aging Conditions ◽

Old Rats ◽

Spectral Counts ◽

Standard Protein

Urine is a very good source for biomarker discovery because it accumulates the changes of body. The urinary proteome is influenced by various factors, which is a major challenge in urinary biomarker discovery. To circumvent these problems, simpler systems, such as animal models, should be used to establish associations between physiological or pathological conditions and changes in the urinary proteome. In this study, the urinary proteome of young (2-month-old) and old rats (20-month-old; 9 in each group) were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between young and old rats. Based on the criteria of a fold change ≥ 2, P < 0.05 and being identified in each rat in the high abundance group, 33 proteins were changed (15 up-regulated and 18 down-regulated in old rats). By adding a more stringent standard (protein spectral counts from every rat in the higher group greater than those in the lower group), 8 proteins were changed consistently in all rats of between the groups, 2 of which are also altered in the urinary proteome of aging humans. There are no shared proteins between our results and the previous aging plasma proteome. Twenty of the 33 (60 %) changed proteins have been reported to be disease biomarkers, which implies that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs, which are strongly expressed in the kidney, intestine, cerebellum and lung, according to the human protein ATLAS. Therefore, the urinary proteome may reflect aging conditions in these organs.

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Urinary proteome profiling for stratifying patients with familial Parkinson’s disease

10.1101/2020.08.09.243584 ◽

2020 ◽

Cited By ~ 1

Author(s):

Sebastian Virreira Winter ◽

Ozge Karayel ◽

Maximilian T Strauss ◽

Shalini Padmanabhan ◽

Matthew Surface ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Biomarker Discovery ◽

Treatment Strategies ◽

Disease Manifestation ◽

Proteome Profiling ◽

Urinary Proteome ◽

G2019s Mutation ◽

Associated Proteins ◽

Novel Treatment Strategies

SUMMARYThe prevalence of Parkinson’s disease (PD) is increasing but the development of novel treatment strategies and therapeutics altering the course of the disease would benefit from specific, sensitive and non-invasive biomarkers to detect PD early. Here, we describe a scalable and sensitive mass spectrometry (MS)-based proteomic workflow for urinary proteome profiling. Our workflow enabled the reproducible quantification of more than 2,000 proteins in more than 200 urine samples using minimal volumes from two independent patient cohorts. The urinary proteome was significantly different between PD patients and healthy controls, as well as between LRRK2 G2019S carriers and non-carriers in both cohorts. Interestingly, our data revealed lysosomal dysregulation in individuals with the LRRK2 G2019S mutation. When combined with machine learning, the urinary proteome data alone was sufficient to classify mutation status and disease manifestation in mutation carriers remarkably well, identifying VGF, ENPEP and other PD-associated proteins as the most discriminating features. Taken together, our results validate urinary proteomics as a valuable strategy for biomarker discovery and patient stratification in PD.

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