Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy

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dc.contributor.authorBloom, Chloe Ien_ZA
dc.contributor.authorGraham, Christine Men_ZA
dc.contributor.authorBerry, Matthew P Ren_ZA
dc.contributor.authorWilkinson, Katalin Aen_ZA
dc.contributor.authorOni, Toluen_ZA
dc.contributor.authorRozakeas, Fotinien_ZA
dc.contributor.authorXu, Zhaohuien_ZA
dc.contributor.authorRossello-Urgell, Joseen_ZA
dc.contributor.authorChaussabel, Damienen_ZA
dc.contributor.authorBanchereau, Jacquesen_ZA
dc.date.accessioned2016-01-11T06:53:19Z
dc.date.available2016-01-11T06:53:19Z
dc.date.issued2012en_ZA
dc.description.abstractRationale: Globally there are approximately 9 million new active tuberculosis cases and 1.4 million deaths annually . Effective antituberculosis treatment monitoring is difficult as there are no existing biomarkers of poor adherence or inadequate treatment earlier than 2 months after treatment initiation. Inadequate treatment leads to worsening disease, disease transmission and drug resistance. Objectives To determine if blood transcriptional signatures change in response to antituberculosis treatment and could act as early biomarkers of a successful response. METHODS: Blood transcriptional profiles of untreated active tuberculosis patients in South Africa were analysed before, during (2 weeks and 2 months), at the end of (6 months) and after (12 months) antituberculosis treatment, and compared to individuals with latent tuberculosis. An active-tuberculosis transcriptional signature and a specific treatment-response transcriptional signature were derived. The specific treatment response transcriptional signature was tested in two independent cohorts. Two quantitative scoring algorithms were applied to measure the changes in the transcriptional response. The most significantly represented pathways were determined using Ingenuity Pathway Analysis. RESULTS: An active tuberculosis 664-transcript signature and a treatment specific 320-transcript signature significantly diminished after 2 weeks of treatment in all cohorts, and continued to diminish until 6 months. The transcriptional response to treatment could be individually measured in each patient. CONCLUSIONS: Significant changes in the transcriptional signatures measured by blood tests were readily detectable just 2 weeks after treatment initiation. These findings suggest that blood transcriptional signatures could be used as early surrogate biomarkers of successful treatment response.en_ZA
dc.identifier.apacitationBloom, C. I., Graham, C. M., Berry, M. P. R., Wilkinson, K. A., Oni, T., Rozakeas, F., ... Banchereau, J. (2012). Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy. <i>PLoS One</i>, http://hdl.handle.net/11427/16268en_ZA
dc.identifier.chicagocitationBloom, Chloe I, Christine M Graham, Matthew P R Berry, Katalin A Wilkinson, Tolu Oni, Fotini Rozakeas, Zhaohui Xu, Jose Rossello-Urgell, Damien Chaussabel, and Jacques Banchereau "Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/16268en_ZA
dc.identifier.citationBloom, C. I., Graham, C. M., Berry, M. P., Wilkinson, K. A., Oni, T., Rozakeas, F., ... & Pascual, V. (2012). Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy. PLoS ONE 7(10), e46191. doi:10.1371/journal.pone.0046191en_ZA
dc.identifier.ris TY - Journal Article AU - Bloom, Chloe I AU - Graham, Christine M AU - Berry, Matthew P R AU - Wilkinson, Katalin A AU - Oni, Tolu AU - Rozakeas, Fotini AU - Xu, Zhaohui AU - Rossello-Urgell, Jose AU - Chaussabel, Damien AU - Banchereau, Jacques AB - Rationale: Globally there are approximately 9 million new active tuberculosis cases and 1.4 million deaths annually . Effective antituberculosis treatment monitoring is difficult as there are no existing biomarkers of poor adherence or inadequate treatment earlier than 2 months after treatment initiation. Inadequate treatment leads to worsening disease, disease transmission and drug resistance. Objectives To determine if blood transcriptional signatures change in response to antituberculosis treatment and could act as early biomarkers of a successful response. METHODS: Blood transcriptional profiles of untreated active tuberculosis patients in South Africa were analysed before, during (2 weeks and 2 months), at the end of (6 months) and after (12 months) antituberculosis treatment, and compared to individuals with latent tuberculosis. An active-tuberculosis transcriptional signature and a specific treatment-response transcriptional signature were derived. The specific treatment response transcriptional signature was tested in two independent cohorts. Two quantitative scoring algorithms were applied to measure the changes in the transcriptional response. The most significantly represented pathways were determined using Ingenuity Pathway Analysis. RESULTS: An active tuberculosis 664-transcript signature and a treatment specific 320-transcript signature significantly diminished after 2 weeks of treatment in all cohorts, and continued to diminish until 6 months. The transcriptional response to treatment could be individually measured in each patient. CONCLUSIONS: Significant changes in the transcriptional signatures measured by blood tests were readily detectable just 2 weeks after treatment initiation. These findings suggest that blood transcriptional signatures could be used as early surrogate biomarkers of successful treatment response. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0046191 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy TI - Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy UR - http://hdl.handle.net/11427/16268 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16268
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0046191
dc.identifier.vancouvercitationBloom CI, Graham CM, Berry MPR, Wilkinson KA, Oni T, Rozakeas F, et al. Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy. PLoS One. 2012; http://hdl.handle.net/11427/16268.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© Bloom et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherBlooden_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherBiomarkersen_ZA
dc.subject.otherDNA transcriptionen_ZA
dc.subject.otherGene expressionen_ZA
dc.subject.otherDrug therapyen_ZA
dc.subject.otherSouth Africaen_ZA
dc.titleDetectable changes in the blood transcriptome are present after two weeks of antituberculosis therapyen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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