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pmid:37219084
Deep Proteomics Network and Machine Learning Analysis of Human Cerebrospinal Fluid in Japanese Encephalitis Virus Infection.
Tehmina Bharucha · Bevin Gangadharan · Abhinav Kumar · Ashleigh C Myall · Nazli Ayhan · Boris Pastorino · Anisone Chanthongthip · Manivanh Vongsouvath · Mayfong Mayxay · Onanong Sengvilaipaseuth · Ooyanong Phonemixay · Sayaphet Rattanavong · Darragh P O'Brien · Iolanda Vendrell · Roman Fischer · Benedikt Kessler · Lance Turtle · Xavier de Lamballerie · Audrey Dubot-Pérès · Paul N Newton · Nicole Zitzmann · SEAe Consortium
Journal of proteome research · 2023 doi:10.1021/acs.jproteome.2c00563
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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We aimed to test the hypothesis of a Japanese encephalitis (JE) protein signature in human cerebrospinal fluid (CSF) that could be harnessed in a rapid diagnostic test (RDT), contribute to understanding the host response and predict outcome during infection. Liquid chromatography and tandem mass spectrometry (LC-MS/MS), using extensive offline fractionation and tandem mass tag labeling (TMT), enabled comparison of the deep CSF proteome in JE vs other confirmed neurological infections (non-JE). Verification was performed using data-independent acquisition (DIA) LC-MS/MS. 5,070 proteins were identified, including 4,805 human proteins and 265 pathogen proteins. Feature selection and predictive modeling using TMT analysis of 147 patient samples enabled the development of a nine-protein JE diagnostic signature. This was tested using DIA analysis of an independent group of 16 patient samples, demonstrating 82% accuracy. Ultimately, validation in a larger group of patients and different locations could help refine the list to 2-3 proteins for an RDT. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD034789 and 10.6019/PXD034789.", "claims": [{"id": "claim-method", "statement": "Differential expression between the protein abundance in the JE vs non-JE patient samples was performed using a t test and Benjamini–Hochberg correction for multiple testing.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37219084", "locator": "sections[8] \"TMT LC–MS/MS Data Differential Protein Expression\" paragraph 2", "quote": "Differential expression between the protein abundance in the JE vs non-JE patient samples was performed using a t test and Benjamini–Hochberg correction for multiple testing."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium92 via the PRIDE partner repository with the dataset identifier PXD034789 and 10.6019/PXD034789. 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