Effects of blood contamination and the rostro-caudal gradient on the human cerebrospinal fluid proteome.

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We present three proteomics studies examining the effect of blood contamination and the rostro-caudal gradient (RCG) on the cerebrospinal fluid (CSF) proteome, in addition to plasma/CSF protein ratios. The studies showed that the central nervous system (CNS) derived proteins appeared to be unaffected by the RCG, while the plasma-derived proteins showed an increase in concentration towards the lumbar area. This implies that the concentration of the plasma-derived proteins in CSF will vary depending on the volume of CSF that is collected. In the CSF samples spiked with blood, 262 of 814 quantified proteins showed an abundance increase of more than 1.5 fold, while 403 proteins had a fold change of less than 1.2 and appeared to be unaffected by blood contamination. Proteins with a high plasma/CSF ratio appeared to give the largest effect on the CSF proteome upon blood contamination. The results give important background information on how factors like blood contamination, RCG and blood-CNS-barrier influences the CSF proteome. This information is particularly important in the field of biomarker discovery, but also for routine clinical measurements. The data from the blood contamination and RCG discovery studies have been deposited to the ProteomeXchange with identifier PXD000401.", "claims": [{"id": "claim-method", "statement": "The 262 proteins with an abundance increase of 1.5 fold in either of the two spike-in levels were defined as affected by the blood contamination, while 403 proteins had a fold change of less than 1.2 in both experiments and were defined as not affected.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:24599184", "locator": "sections[16] \"Effect of blood contamination\" paragraph 3", "quote": "The 262 proteins with an abundance increase of 1.5 fold in either of the two spike-in levels were defined as affected by the blood contamination, while 403 proteins had a fold change of less than 1.2 in both experiments and were defined as not affected."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data from the blood contamination and RCG discovery studies have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository [30] with the dataset identifier PXD000401.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:24599184", "locator": "sections[23] \"Supporting information\" paragraph 2", "quote": "The mass spectrometry proteomics data from the blood contamination and RCG discovery studies have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository [30] with the dataset identifier PXD000401."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Blood contamination was evaluated by fold-change classification: 262 of 814 quantified proteins were affected, 403 were unaffected, and 149 were uncertain, with the source data reported in Table S2.", "kind": "quantitative", "target": {"value": 1.5, "unit": "fold change", "tolerance": null, "source": "The 262 proteins with an abundance increase of 1.5 fold in either of the two spike-in levels were defined as affected by the blood contamination, while 403 proteins had a fold change of less than 1.2 in both experiments and were defined as not affected."}, "evidence": [{"asset": "source:pmid:24599184", "locator": "sections[16] \"Effect of blood contamination\" paragraph 3", "quote": "The 262 proteins with an abundance increase of 1.5 fold in either of the two spike-in levels were defined as affected by the blood contamination, while 403 proteins had a fold change of less than 1.2 in both experiments and were defined as not affected."}, {"asset": "source:pmid:24599184", "locator": "sections[16] \"Effect of blood contamination\" paragraph 3", "quote": "The 149 proteins with observed fold changes between 1.2 and 1.5 were defined as uncertain with respect to being affected by the blood contamination."}, {"asset": "source:pmid:24599184", "locator": "sections[16] \"Effect of blood contamination\" paragraph 3", "quote": "The quantitative information for the 814 proteins for the two comparisons (1) reference versus 0.5% blood and (2) reference versus 2% blood, are given in Table S2."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Blood contamination was evaluated by fold-change classification: 262 of 814 quantified proteins were affected, 403 were unaffected, and 149 were uncertain, with the source data reported in Table S2.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:24599184"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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