Quantitative proteomics for identifying biomarkers for tuberculous meningitis
<p>Abstract</p> <p>Introduction</p> <p>Tuberculous meningitis is a frequent extrapulmonary disease caused by <it>Mycobacterium tuberculosis</it> and is associated with high mortality rates and severe neurological sequelae. In an earlier study employing DNA m...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-11-01
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| Series: | Clinical Proteomics |
| Subjects: | |
| Online Access: | http://www.clinicalproteomicsjournal.com/content/9/1/12 |
| _version_ | 1818834496283213824 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kumar Ghantasala S Sameer |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Introduction</p> <p>Tuberculous meningitis is a frequent extrapulmonary disease caused by <it>Mycobacterium tuberculosis</it> 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.</p> <p>Methods</p> <p>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.</p> <p>Results and conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-19T02:35:44Z |
| format | Article |
| id | doaj.art-b94f83739546429c9005caae0c8ba01c |
| institution | Directory Open Access Journal |
| issn | 1559-0275 |
| language | English |
| last_indexed | 2024-12-19T02:35:44Z |
| publishDate | 2012-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Proteomics |
| spelling | doaj.art-b94f83739546429c9005caae0c8ba01c2022-12-21T20:39:26ZengBMCClinical Proteomics1559-02752012-11-01911210.1186/1559-0275-9-12Quantitative proteomics for identifying biomarkers for tuberculous meningitisKumar Ghantasala S SameerVenugopal Abhilash KMahadevan AnitaRenuse SantoshHarsha H CSahasrabuddhe Nandini APawar HarshSharma RakeshKumar PraveenRajagopalan SudhaWaddell KeithRamachandra Yarappa LSatishchandra ParthasarathyChaerkady RaghothamaPrasad T S KeshavaShankar KPandey Akhilesh<p>Abstract</p> <p>Introduction</p> <p>Tuberculous meningitis is a frequent extrapulmonary disease caused by <it>Mycobacterium tuberculosis</it> 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.</p> <p>Methods</p> <p>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.</p> <p>Results and conclusions</p> <p>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.</p>http://www.clinicalproteomicsjournal.com/content/9/1/12Relative quantitationCerebrospinal fluidHistopathologyEarly diagnosisTuberculosis |
| spellingShingle | 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 Clinical Proteomics Relative quantitation Cerebrospinal fluid Histopathology Early diagnosis Tuberculosis |
| title | Quantitative proteomics for identifying biomarkers for tuberculous meningitis |
| title_full | Quantitative proteomics for identifying biomarkers for tuberculous meningitis |
| title_fullStr | Quantitative proteomics for identifying biomarkers for tuberculous meningitis |
| title_full_unstemmed | Quantitative proteomics for identifying biomarkers for tuberculous meningitis |
| title_short | Quantitative proteomics for identifying biomarkers for tuberculous meningitis |
| title_sort | quantitative proteomics for identifying biomarkers for tuberculous meningitis |
| topic | Relative quantitation Cerebrospinal fluid Histopathology Early diagnosis Tuberculosis |
| url | http://www.clinicalproteomicsjournal.com/content/9/1/12 |
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