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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

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Experiment

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Data

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Deep Proteomics Network and Machine Learning Analysis of Human Cerebrospinal Fluid in Japanese Encephalitis Virus Infection.
doi
10.1021/acs.jproteome.2c00563
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Tehmina Bharucha
[1]
Bevin Gangadharan
[2]
Abhinav Kumar
[3]
Ashleigh C Myall
[4]
Nazli Ayhan
[5]
Boris Pastorino
[6]
Anisone Chanthongthip
[7]
Manivanh Vongsouvath
[8]
Mayfong Mayxay
[9]
Onanong Sengvilaipaseuth
[10]
Ooyanong Phonemixay
[11]
Sayaphet Rattanavong
[12]
Darragh P O'Brien
[13]
Iolanda Vendrell
[14]
Roman Fischer
[15]
Benedikt Kessler
[16]
Lance Turtle
[17]
Xavier de Lamballerie
[18]
Audrey Dubot-Pérès
[19]
Paul N Newton
[20]
Nicole Zitzmann
[21]
SEAe Consortium
journal
Journal of proteome research
year
2023
abstract
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.
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