Quantitative proteomics for identifying biomarkers for rabies

Abhilash K. Venugopal, S. Sameer Kumar Ghantasala, Lakshmi Dhevi N Selvan, Anita Mahadevan, Santosh Renuse, Praveen Kumar, Harsh Pawar, Nandini A. Sahasrabhuddhe, Mooriyath S. Suja, Yarappa L. Ramachandra, Thottethodi S Keshava Prasad, Shampur N. Madhusudhana, H. C. Harsha, Raghothama Chaerkady, Parthasarathy Satishchandra, Akhilesh Pandey, Susarla K. Shankar

Research output: Contribution to journalArticle

Abstract

Introduction: Rabies is a fatal acute viral disease of the central nervous system, which is a serious public health problem in Asian and African countries. Based on the clinical presentation, rabies can be classified into encephalitic (furious) or paralytic (numb) rabies. Early diagnosis of this disease is particularly important as rabies is invariably fatal if adequate post exposure prophylaxis is not administered immediately following the bite. Methods: In this study, we carried out a quantitative proteomic analysis of the human brain tissue from cases of encephalitic and paralytic rabies along with normal human brain tissues using an 8-plex isobaric tags for relative and absolute quantification (iTRAQ) strategy. Results and conclusion: We identified 402 proteins, of which a number of proteins were differentially expressed between encephalitic and paralytic rabies, including several novel proteins. The differentially expressed molecules included karyopherin alpha 4 (KPNA4), which was overexpressed only in paralytic rabies, calcium calmodulin dependent kinase 2 alpha (CAMK2A), which was upregulated in paralytic rabies group and glutamate ammonia ligase (GLUL), which was overexpressed in paralytic as well as encephalitic rabies. We validated two of the upregulated molecules, GLUL and CAMK2A, by dot blot assays and further validated CAMK2A by immunohistochemistry. These molecules need to be further investigated in body fluids such as cerebrospinal fluid in a larger cohort of rabies cases to determine their potential use as antemortem diagnostic biomarkers in rabies. This is the first study to systematically profile clinical subtypes of human rabies using an iTRAQ quantitative proteomics approach.

Original languageEnglish (US)
Article number3
JournalClinical Proteomics
Volume10
Issue number1
DOIs
StatePublished - 2013

Fingerprint

Rabies
Biomarkers
Calmodulin
Proteomics
Glutamate-Ammonia Ligase
Phosphotransferases
Molecules
Brain
alpha Karyopherins
Tissue
Cerebrospinal fluid
Proteins
Body fluids
Neurology
Public health
Medical problems
Calcium-Calmodulin-Dependent Protein Kinases
Assays
Calcium
Post-Exposure Prophylaxis

Keywords

  • Hierarchical cluster
  • Liquid chromatography
  • Mass spectrometry
  • Post exposure vaccination
  • Spectrum mill

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

Cite this

Venugopal, A. K., Ghantasala, S. S. K., Selvan, L. D. N., Mahadevan, A., Renuse, S., Kumar, P., ... Shankar, S. K. (2013). Quantitative proteomics for identifying biomarkers for rabies. Clinical Proteomics, 10(1), [3]. https://doi.org/10.1186/1559-0275-10-3

Quantitative proteomics for identifying biomarkers for rabies. / Venugopal, Abhilash K.; Ghantasala, S. Sameer Kumar; Selvan, Lakshmi Dhevi N; Mahadevan, Anita; Renuse, Santosh; Kumar, Praveen; Pawar, Harsh; Sahasrabhuddhe, Nandini A.; Suja, Mooriyath S.; Ramachandra, Yarappa L.; Prasad, Thottethodi S Keshava; Madhusudhana, Shampur N.; Harsha, H. C.; Chaerkady, Raghothama; Satishchandra, Parthasarathy; Pandey, Akhilesh; Shankar, Susarla K.

In: Clinical Proteomics, Vol. 10, No. 1, 3, 2013.

Research output: Contribution to journalArticle

Venugopal, AK, Ghantasala, SSK, Selvan, LDN, Mahadevan, A, Renuse, S, Kumar, P, Pawar, H, Sahasrabhuddhe, NA, Suja, MS, Ramachandra, YL, Prasad, TSK, Madhusudhana, SN, Harsha, HC, Chaerkady, R, Satishchandra, P, Pandey, A & Shankar, SK 2013, 'Quantitative proteomics for identifying biomarkers for rabies', Clinical Proteomics, vol. 10, no. 1, 3. https://doi.org/10.1186/1559-0275-10-3
Venugopal AK, Ghantasala SSK, Selvan LDN, Mahadevan A, Renuse S, Kumar P et al. Quantitative proteomics for identifying biomarkers for rabies. Clinical Proteomics. 2013;10(1). 3. https://doi.org/10.1186/1559-0275-10-3
Venugopal, Abhilash K. ; Ghantasala, S. Sameer Kumar ; Selvan, Lakshmi Dhevi N ; Mahadevan, Anita ; Renuse, Santosh ; Kumar, Praveen ; Pawar, Harsh ; Sahasrabhuddhe, Nandini A. ; Suja, Mooriyath S. ; Ramachandra, Yarappa L. ; Prasad, Thottethodi S Keshava ; Madhusudhana, Shampur N. ; Harsha, H. C. ; Chaerkady, Raghothama ; Satishchandra, Parthasarathy ; Pandey, Akhilesh ; Shankar, Susarla K. / Quantitative proteomics for identifying biomarkers for rabies. In: Clinical Proteomics. 2013 ; Vol. 10, No. 1.
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AU - Ghantasala, S. Sameer Kumar

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AU - Mahadevan, Anita

AU - Renuse, Santosh

AU - Kumar, Praveen

AU - Pawar, Harsh

AU - Sahasrabhuddhe, Nandini A.

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AU - Ramachandra, Yarappa L.

AU - Prasad, Thottethodi S Keshava

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AU - Harsha, H. C.

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N2 - Introduction: Rabies is a fatal acute viral disease of the central nervous system, which is a serious public health problem in Asian and African countries. Based on the clinical presentation, rabies can be classified into encephalitic (furious) or paralytic (numb) rabies. Early diagnosis of this disease is particularly important as rabies is invariably fatal if adequate post exposure prophylaxis is not administered immediately following the bite. Methods: In this study, we carried out a quantitative proteomic analysis of the human brain tissue from cases of encephalitic and paralytic rabies along with normal human brain tissues using an 8-plex isobaric tags for relative and absolute quantification (iTRAQ) strategy. Results and conclusion: We identified 402 proteins, of which a number of proteins were differentially expressed between encephalitic and paralytic rabies, including several novel proteins. The differentially expressed molecules included karyopherin alpha 4 (KPNA4), which was overexpressed only in paralytic rabies, calcium calmodulin dependent kinase 2 alpha (CAMK2A), which was upregulated in paralytic rabies group and glutamate ammonia ligase (GLUL), which was overexpressed in paralytic as well as encephalitic rabies. We validated two of the upregulated molecules, GLUL and CAMK2A, by dot blot assays and further validated CAMK2A by immunohistochemistry. These molecules need to be further investigated in body fluids such as cerebrospinal fluid in a larger cohort of rabies cases to determine their potential use as antemortem diagnostic biomarkers in rabies. This is the first study to systematically profile clinical subtypes of human rabies using an iTRAQ quantitative proteomics approach.

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