Serum proteome and cytokine analysis in a longitudinal cohort of adults with primary dengue infection reveals predictive markers of DHF

Background: Infections caused by dengue virus are a major cause of morbidity and mortality in tropical and subtropical regions of the world. Factors that control transition from mild forms of disease such as dengue fever (DF) to more life-threatening forms such as dengue hemorrhagic fever (DHF) are...

Full description

Bibliographic Details
Main Authors: Rajapakse, Jagath C., Tannenbaum, Steven R., Kumar, Yadunanda, Liang, Cui, Bo, Zheng, Ooi, Eng Eong
Other Authors: School of Computer Engineering
Format: Journal Article
Language:English
Published: 2013
Subjects:
Online Access:https://hdl.handle.net/10356/79487
http://hdl.handle.net/10220/10923
_version_ 1811681303947378688
author Rajapakse, Jagath C.
Tannenbaum, Steven R.
Kumar, Yadunanda
Liang, Cui
Bo, Zheng
Ooi, Eng Eong
author2 School of Computer Engineering
author_facet School of Computer Engineering
Rajapakse, Jagath C.
Tannenbaum, Steven R.
Kumar, Yadunanda
Liang, Cui
Bo, Zheng
Ooi, Eng Eong
author_sort Rajapakse, Jagath C.
collection NTU
description Background: Infections caused by dengue virus are a major cause of morbidity and mortality in tropical and subtropical regions of the world. Factors that control transition from mild forms of disease such as dengue fever (DF) to more life-threatening forms such as dengue hemorrhagic fever (DHF) are poorly understood. Consequently, there are no reliable methods currently available for early triage of DHF patients resulting in significant over-hospitalization. Methodology/Principal Findings:We have systematically examined the proteome, cytokines and inflammatory markers in sera from 62 adult dengue patients (44 DF; 18 DHF) with primary DENV infection, at three different times of infection representing the early febrile, defervescence and convalescent stages. Using fluorescent bioplex assays, we measured 27 cytokines in these serum samples. Additionally, we used multiple mass spectrometry methods for iTRAQ-based comparative analysis of serum proteome as well as measurements of protein adducts- 3-nitrotyrosine and 3-chlorotyrosine as surrogate measures of free radical activity. Using multiple methods such as OPLS, MRMR and MSVM-RFE for multivariate feature selection and classification, we report molecular markers that allow prediction of primary DHF with sensitivity and specificity of >80%. Conclusions/Significance: This report constitutes a comprehensive analysis of molecular signatures of dengue disease progression and will help unravel mechanisms of dengue disease progression. Our analysis resulted in the identification of markers that may be useful for early prediction of DHF during the febrile phase. The combination of highly sensitive analytical methods and novel statistical approaches described here forms a robust platform for biomarker discovery.
first_indexed 2024-10-01T03:38:49Z
format Journal Article
id ntu-10356/79487
institution Nanyang Technological University
language English
last_indexed 2024-10-01T03:38:49Z
publishDate 2013
record_format dspace
spelling ntu-10356/794872022-02-16T16:30:24Z Serum proteome and cytokine analysis in a longitudinal cohort of adults with primary dengue infection reveals predictive markers of DHF Rajapakse, Jagath C. Tannenbaum, Steven R. Kumar, Yadunanda Liang, Cui Bo, Zheng Ooi, Eng Eong School of Computer Engineering DRNTU::Engineering::Computer science and engineering Background: Infections caused by dengue virus are a major cause of morbidity and mortality in tropical and subtropical regions of the world. Factors that control transition from mild forms of disease such as dengue fever (DF) to more life-threatening forms such as dengue hemorrhagic fever (DHF) are poorly understood. Consequently, there are no reliable methods currently available for early triage of DHF patients resulting in significant over-hospitalization. Methodology/Principal Findings:We have systematically examined the proteome, cytokines and inflammatory markers in sera from 62 adult dengue patients (44 DF; 18 DHF) with primary DENV infection, at three different times of infection representing the early febrile, defervescence and convalescent stages. Using fluorescent bioplex assays, we measured 27 cytokines in these serum samples. Additionally, we used multiple mass spectrometry methods for iTRAQ-based comparative analysis of serum proteome as well as measurements of protein adducts- 3-nitrotyrosine and 3-chlorotyrosine as surrogate measures of free radical activity. Using multiple methods such as OPLS, MRMR and MSVM-RFE for multivariate feature selection and classification, we report molecular markers that allow prediction of primary DHF with sensitivity and specificity of >80%. Conclusions/Significance: This report constitutes a comprehensive analysis of molecular signatures of dengue disease progression and will help unravel mechanisms of dengue disease progression. Our analysis resulted in the identification of markers that may be useful for early prediction of DHF during the febrile phase. The combination of highly sensitive analytical methods and novel statistical approaches described here forms a robust platform for biomarker discovery. Published version 2013-07-04T02:22:07Z 2019-12-06T13:26:32Z 2013-07-04T02:22:07Z 2019-12-06T13:26:32Z 2012 2012 Journal Article Kumar, Y., Liang, C., Bo, Z., Rajapakse, J. C., Ooi, E. E., & Tannenbaum, S. R. (2012). Serum Proteome and Cytokine Analysis in a Longitudinal Cohort of Adults with Primary Dengue Infection Reveals Predictive Markers of DHF. PLoS Neglected Tropical Diseases, 6(11), e1887. 1935-2735 https://hdl.handle.net/10356/79487 http://hdl.handle.net/10220/10923 10.1371/journal.pntd.0001887 23209847 en PLoS neglected tropical diseases © 2012 The Authors. This paper was published in PLoS Neglected Tropical Diseases and is made available as an electronic reprint (preprint) with permission of The Authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1371/journal.pntd.0001887]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf
spellingShingle DRNTU::Engineering::Computer science and engineering
Rajapakse, Jagath C.
Tannenbaum, Steven R.
Kumar, Yadunanda
Liang, Cui
Bo, Zheng
Ooi, Eng Eong
Serum proteome and cytokine analysis in a longitudinal cohort of adults with primary dengue infection reveals predictive markers of DHF
title Serum proteome and cytokine analysis in a longitudinal cohort of adults with primary dengue infection reveals predictive markers of DHF
title_full Serum proteome and cytokine analysis in a longitudinal cohort of adults with primary dengue infection reveals predictive markers of DHF
title_fullStr Serum proteome and cytokine analysis in a longitudinal cohort of adults with primary dengue infection reveals predictive markers of DHF
title_full_unstemmed Serum proteome and cytokine analysis in a longitudinal cohort of adults with primary dengue infection reveals predictive markers of DHF
title_short Serum proteome and cytokine analysis in a longitudinal cohort of adults with primary dengue infection reveals predictive markers of DHF
title_sort serum proteome and cytokine analysis in a longitudinal cohort of adults with primary dengue infection reveals predictive markers of dhf
topic DRNTU::Engineering::Computer science and engineering
url https://hdl.handle.net/10356/79487
http://hdl.handle.net/10220/10923
work_keys_str_mv AT rajapaksejagathc serumproteomeandcytokineanalysisinalongitudinalcohortofadultswithprimarydengueinfectionrevealspredictivemarkersofdhf
AT tannenbaumstevenr serumproteomeandcytokineanalysisinalongitudinalcohortofadultswithprimarydengueinfectionrevealspredictivemarkersofdhf
AT kumaryadunanda serumproteomeandcytokineanalysisinalongitudinalcohortofadultswithprimarydengueinfectionrevealspredictivemarkersofdhf
AT liangcui serumproteomeandcytokineanalysisinalongitudinalcohortofadultswithprimarydengueinfectionrevealspredictivemarkersofdhf
AT bozheng serumproteomeandcytokineanalysisinalongitudinalcohortofadultswithprimarydengueinfectionrevealspredictivemarkersofdhf
AT ooiengeong serumproteomeandcytokineanalysisinalongitudinalcohortofadultswithprimarydengueinfectionrevealspredictivemarkersofdhf