Deep Proteomics Network and Machine Learning Analysis of Human Cerebrospinal Fluid in Japanese Encephalitis Virus Infection

Bharucha, Tehmina, Gangadharan, Bevin, Kumar, Abhinav, Myall, Ashleigh C, Ayhan, Nazli, Pastorino, Boris, Chanthongthip, Anisone, Vongsouvath, Manivanh, Mayxay, Mayfong, Sengvilaipaseuth, Onanong
et al (show 12 more authors) (2023) Deep Proteomics Network and Machine Learning Analysis of Human Cerebrospinal Fluid in Japanese Encephalitis Virus Infection. JOURNAL OF PROTEOME RESEARCH, 22 (6). pp. 1614-1629.

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Japanese encephalitis virus is a leading cause of neurological infection in the Asia-Pacific region with no means of detection in more remote areas. 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.

Item Type: Article
Uncontrolled Keywords: central nervous system infection, neurological infection, encephalitis, flavivirus, Japanese encephalitis virus, diagnosis, clinical proteomics, mass spectrometry, tandem mass tagging, data-independent acquisition, network analysis, machine learning analysis, predictive modeling, Lao PDR
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 24 Jul 2023 14:55
Last Modified: 24 Jul 2023 14:55
DOI: 10.1021/acs.jproteome.2c00563
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