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Proof-of-Concept Workflow for Establishing Reference Intervals of Human Urine Proteome for Monitoring Physiological and Pathological Changes.

ABSTRACT: Urine as a true non-invasive sampling source holds great potential for biomarker discovery. While approximately 2000 proteins can be detected by mass spectrometry in urine from healthy people, the amount of these proteins vary considerably. A systematic evaluation of a large number of samples is needed to determine the range of the variations. Current biomarker studies often measure limited number of urine samples in the discovery phase, which makes it difficult to determine whether proteins differentially expressed between control and disease groups represent actual difference, or are just physiological variations among the individuals, leads to failures in the validation phase with the increased sample numbers. Here, we report a streamlined workflow with capacity of measuring 8 urine proteomes per day at the coverage of >1500 proteins. With this workflow, we evaluated variations in 497 urine proteomes from 167 healthy donors, establishing reference intervals (RIs) that covered urine protein variations. We demonstrated that RIs could be used to monitor physiological changes by detecting transient outlier proteins. Furthermore, we provided a RIs-based algorithm for biomarker discovery and validation to screen for diseases such as cancer. This study provided a proof-of-principle workflow for the use of urine proteome for health monitoring and disease screening.

SUBMITTER: Leng W

PROVIDER: S-EPMC5405183 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Proof-of-Concept Workflow for Establishing Reference Intervals of Human Urine Proteome for Monitoring Physiological and Pathological Changes.

Leng Wenchuan W Ni Xiaotian X Sun Changqing C Lu Tianyuan T Malovannaya Anna A Jung Sung Yun SY Huang Yin Y Qiu Yang Y Sun Guannan G Holt Matthew V MV Ding Chen C Sun Wei W Men Xuebo X Shi Tieliu T Zhu Weimin W Wang Yi Y He Fuchu F Zhen Bei B Wang Guangshun G Qin Jun J

EBioMedicine 20170322

Urine as a true non-invasive sampling source holds great potential for biomarker discovery. While approximately 2000 proteins can be detected by mass spectrometry in urine from healthy people, the amount of these proteins vary considerably. A systematic evaluation of a large number of samples is needed to determine the range of the variations. Current biomarker studies often measure limited number of urine samples in the discovery phase, which makes it difficult to determine whether proteins dif ...[more]

PMID: 28396014

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Project description:BackgroundAbnormal intra-pregnancy haematological variables are associated with adverse feto-maternal outcomes. However, the reference intervals (RIs) employed in sub-Saharan Africa to inform clinical decisions are generally imported. Since RIs are influenced by age, geographical location, and race, we hypothesized that context specific RIs should be established in Ghana to contextualize intra-pregnancy decision making.MethodsThis cross-sectional study retrospectively retrieved data of 333 pregnant women with no known clinically determined intra-pregnancy complications; 22 participants in their first trimester (T1; 1-13 weeks), 177 in their T2 (14-27 weeks), and 132 in T3 (28-41 weeks). RIs for haematological parameters were non-parametrically determined at 2.5th and 97.5th percentiles in accordance with CLSI guidance document EP28-A3c. Two-sample comparisons were undertaken using Wilcoxon rank-sum tests whereas more than two-sample comparisons were undertaken using Kruskal-Wallis test. Statistical significance was set at p <0.05 under the two-tailed assumptions.ResultsIn accordance with WHO trimester-specific haemoglobin cutoffs, anaemia prevalence was a moderate (T1: 36.4%; 8/22 & T2: 31.6%; 56/177) to severe (T3:68.0%; 90/132) public health problem. Additionally, 9.3% (31/333) individuals had high gestational haemoglobin levels (Hb >13.0 g/dL). Moreover, haemoglobin (T2: 8.6-14.3 vs T3: 7.5-13.6 g/dL), MCH (T2: 22.5-69.8 vs T3: 21.6-31.9 pg), MCHC (T2: 30.2-51.8 g/L vs T3: 30.5-37.9 g/L), TWBC (T2: 4.0-13.4 vs T3: 4.1-13.0 x 109/L) required trimester specific RIs, compared to RBC (2.8-5.1 x 1012/L), MCV (66.2-100.2 fL), and platelet counts (106.3-388.3 x 109/L) that each required combined reference intervals.ConclusionsThe intra-pregnancy haematological RIs determined have appreciable lower limits; there is the need to determine context-specific thresholds for haematological variables predictive of positive and/or adverse maternal and infant health outcomes.

Dataset Information

Proof-of-Concept Workflow for Establishing Reference Intervals of Human Urine Proteome for Monitoring Physiological and Pathological Changes.

Publications

Proof-of-Concept Workflow for Establishing Reference Intervals of Human Urine Proteome for Monitoring Physiological and Pathological Changes.

Similar Datasets

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