Quantitative proteomics for identifying biomarkers for tuberculous meningitis

Ghantasala S.Sameer Kumar, Abhilash K. Venugopal, Anita Mahadevan, Santosh Renuse, H. C. Harsha, Nandini A. Sahasrabuddhe, Harsh Pawar, Rakesh Sharma, Praveen Kumar, Sudha Rajagopalan, Keith Waddell, Yarappa L. Ramachandra, Parthasarathy Satishchandra, Raghothama Chaerkady, T. S.Keshava Prasad, K. Shankar, Akhilesh Pandey

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Introduction: Tuberculous meningitis is a frequent extrapulmonary disease caused by Mycobacterium tuberculosis and is associated with high mortality rates and severe neurological sequelae. In an earlier study employing DNA microarrays, we had identified genes that were differentially expressed at the transcript level in human brain tissue from cases of tuberculous meningitis. In the current study, we used a quantitative proteomics approach to discover protein biomarkers for tuberculous meningitis. Methods: To compare brain tissues from confirmed cased of tuberculous meningitis with uninfected brain tissue, we carried out quantitative protein expression profiling using iTRAQ labeling and LC-MS/MS analysis of SCX fractionated peptides on Agilent's accurate mass QTOF mass spectrometer. Results and conclusions: Through this approach, we identified both known and novel differentially regulated molecules. Those described previously included signal-regulatory protein alpha (SIRPA) and protein disulfide isomerase family A, member 6 (PDIA6), which have been shown to be overexpressed at the mRNA level in tuberculous meningitis. The novel overexpressed proteins identified in our study included amphiphysin (AMPH) and neurofascin (NFASC) while ferritin light chain (FTL) was found to be downregulated in TBM. We validated amphiphysin, neurofascin and ferritin light chain using immunohistochemistry which confirmed their differential expression in tuberculous meningitis. Overall, our data provides insights into the host response in tuberculous meningitis at the molecular level in addition to providing candidate diagnostic biomarkers for tuberculous meningitis.

Original languageEnglish (US)
Article number12
JournalClinical Proteomics
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Fingerprint

Meningeal Tuberculosis
Biomarkers
Proteomics
Apoferritins
Brain
Tissue
Proteins
Protein Disulfide-Isomerases
Mass spectrometers
Microarrays
Labeling
Genes
Messenger RNA
Peptides
Molecules
DNA
Oligonucleotide Array Sequence Analysis
Mycobacterium tuberculosis
Down-Regulation
Immunohistochemistry

Keywords

  • Cerebrospinal fluid
  • Early diagnosis
  • Histopathology
  • Relative quantitation
  • Tuberculosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Kumar, G. S. S., Venugopal, A. K., Mahadevan, A., Renuse, S., Harsha, H. C., Sahasrabuddhe, N. A., ... Pandey, A. (2012). Quantitative proteomics for identifying biomarkers for tuberculous meningitis. Clinical Proteomics, 9(1), [12]. https://doi.org/10.1186/1559-0275-9-12

Quantitative proteomics for identifying biomarkers for tuberculous meningitis. / Kumar, Ghantasala S.Sameer; Venugopal, Abhilash K.; Mahadevan, Anita; Renuse, Santosh; Harsha, H. C.; Sahasrabuddhe, Nandini A.; Pawar, Harsh; Sharma, Rakesh; Kumar, Praveen; Rajagopalan, Sudha; Waddell, Keith; Ramachandra, Yarappa L.; Satishchandra, Parthasarathy; Chaerkady, Raghothama; Prasad, T. S.Keshava; Shankar, K.; Pandey, Akhilesh.

In: Clinical Proteomics, Vol. 9, No. 1, 12, 01.01.2012.

Research output: Contribution to journalArticle

Kumar, GSS, Venugopal, AK, Mahadevan, A, Renuse, S, Harsha, HC, Sahasrabuddhe, NA, Pawar, H, Sharma, R, Kumar, P, Rajagopalan, S, Waddell, K, Ramachandra, YL, Satishchandra, P, Chaerkady, R, Prasad, TSK, Shankar, K & Pandey, A 2012, 'Quantitative proteomics for identifying biomarkers for tuberculous meningitis', Clinical Proteomics, vol. 9, no. 1, 12. https://doi.org/10.1186/1559-0275-9-12
Kumar GSS, Venugopal AK, Mahadevan A, Renuse S, Harsha HC, Sahasrabuddhe NA et al. Quantitative proteomics for identifying biomarkers for tuberculous meningitis. Clinical Proteomics. 2012 Jan 1;9(1). 12. https://doi.org/10.1186/1559-0275-9-12
Kumar, Ghantasala S.Sameer ; Venugopal, Abhilash K. ; Mahadevan, Anita ; Renuse, Santosh ; Harsha, H. C. ; Sahasrabuddhe, Nandini A. ; Pawar, Harsh ; Sharma, Rakesh ; Kumar, Praveen ; Rajagopalan, Sudha ; Waddell, Keith ; Ramachandra, Yarappa L. ; Satishchandra, Parthasarathy ; Chaerkady, Raghothama ; Prasad, T. S.Keshava ; Shankar, K. ; Pandey, Akhilesh. / Quantitative proteomics for identifying biomarkers for tuberculous meningitis. In: Clinical Proteomics. 2012 ; Vol. 9, No. 1.
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AU - Venugopal, Abhilash K.

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AU - Sharma, Rakesh

AU - Kumar, Praveen

AU - Rajagopalan, Sudha

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AU - Chaerkady, Raghothama

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N2 - Introduction: Tuberculous meningitis is a frequent extrapulmonary disease caused by Mycobacterium tuberculosis and is associated with high mortality rates and severe neurological sequelae. In an earlier study employing DNA microarrays, we had identified genes that were differentially expressed at the transcript level in human brain tissue from cases of tuberculous meningitis. In the current study, we used a quantitative proteomics approach to discover protein biomarkers for tuberculous meningitis. Methods: To compare brain tissues from confirmed cased of tuberculous meningitis with uninfected brain tissue, we carried out quantitative protein expression profiling using iTRAQ labeling and LC-MS/MS analysis of SCX fractionated peptides on Agilent's accurate mass QTOF mass spectrometer. Results and conclusions: Through this approach, we identified both known and novel differentially regulated molecules. Those described previously included signal-regulatory protein alpha (SIRPA) and protein disulfide isomerase family A, member 6 (PDIA6), which have been shown to be overexpressed at the mRNA level in tuberculous meningitis. The novel overexpressed proteins identified in our study included amphiphysin (AMPH) and neurofascin (NFASC) while ferritin light chain (FTL) was found to be downregulated in TBM. We validated amphiphysin, neurofascin and ferritin light chain using immunohistochemistry which confirmed their differential expression in tuberculous meningitis. Overall, our data provides insights into the host response in tuberculous meningitis at the molecular level in addition to providing candidate diagnostic biomarkers for tuberculous meningitis.

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KW - Relative quantitation

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