Mass spectrometry-based quantification of proteins and post-translational modifications in dried blood: longitudinal sampling of patients with sepsis in Tanzania.

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Whole blood is commonly separated into soluble and cellular fractions. However, this can introduce pre-analytical variability; and analysis of a single component (which is common) may ignore important pathophysiology. We have recently developed methods for the facile processing of dried blood for mass spectrometry-based quantification of the proteome, N-glycoproteome and phosphoproteome. Here, we applied this approach to 38 patients in Tanzania who presented to the hospital with sepsis. Blood was collected on Mitra devices at presentation and 1, 3 and 28-42 days post-enrollment. Processing of 96 total samples was performed in plate-based formats and completed within two days. Approximately 2,000 protein groups and 8,000 post-translational modifications were quantified in 3 LC-MS/MS runs at ~1.5 hours per sample. Analysis of differential abundance revealed blood proteome signatures of acute phase response and neutrophilic inflammation that partially resolved at the 28-42 day timepoint. Numerous analytes correlated with clinical laboratory values for c-reactive protein and white blood cell counts, as well as the Universal Vital Assessment illness severity score. These datasets serve as proof-of-concept for large scale MS-based (sub)phenotyping of disease using dried blood and are available via the ProteomeXchange consortium (PXD060377).", "claims": [{"id": "claim-method", "statement": "Comparisons between d0 and d28–42 timepoints used paired t-tests with Benjamini-Hochberg FDR correction.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40492198", "locator": "sections[11] \"Statistical analysis.\" paragraph 2", "quote": "Comparisons between d0 and d28–42 timepoints used paired t-tests with Benjamini-Hochberg FDR correction."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Approximately 2,000 protein groups and 8,000 post-translational modifications were quantified in 3 LC-MS/MS runs at ~1.5 hours per sample.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40492198", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Approximately 2,000 protein groups and 8,000 post-translational modifications were quantified in 3 LC-MS/MS runs at ~1.5 hours per sample."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Approximately 2,000 protein groups and 8,000 post-translational modifications were quantified in 3 LC-MS/MS runs at ~1.5 hours per sample.", "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:40492198"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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