The application of transcriptional blood signatures to enhance our understanding of the host response to infection: the example of tuberculosis

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Abstract

Despite advances in antimicrobials, vaccination and public health measures, infectious diseases remain a leading cause of morbidity and mortality worldwide. With the increase in antimicrobial resistance and the emergence of new pathogens, there remains a need for new and more accurate diagnostics, the ability to monitor adequate treatment response as well as the ability to predict prognosis for an individual. Transcriptional approaches using blood signatures have enabled a better understanding of the host response to diseases, leading not only to new avenues of basic research, but also to the identification of potential biomarkers for use in diagnosis, prognosis and treatment monitoring.

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RNA-Seq: a revolutionary tool for transcriptomics.

Zhong Wang, Mark Gerstein, Michael Snyder (2009)

RNA-Seq is a recently developed approach to transcriptome profiling that uses deep-sequencing technologies. Studies using this method have already altered our view of the extent and complexity of eukaryotic transcriptomes. RNA-Seq also provides a far more precise measurement of levels of transcripts and their isoforms than other methods. This article describes the RNA-Seq approach, the challenges associated with its application, and the advances made so far in characterizing several eukaryote transcriptomes.

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Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.

Troy Querec, Rama Akondy, Eva K. Lee … (2009)

A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4-an orchestrator of the integrated stress response-that correlated with and predicted YF-17D CD8(+) T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy.

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Systems Biology of Seasonal Influenza Vaccination in Humans

Helder Nakaya, Jens Wrammert, Eva K. Lee … (2011)

We used a systems biological approach to study innate and adaptive responses to influenza vaccination in humans, during 3 consecutive influenza seasons. Healthy adults were vaccinated with inactivated (TIV) or live attenuated (LAIV) influenza vaccines. TIV induced greater antibody titers and enhanced numbers of plasmablasts than LAIV. In TIV vaccinees, early molecular signatures correlated with, and accurately predicted, later antibody titers in two independent trials. Interestingly, the expression of Calcium/calmodulin-dependent kinase IV (CamkIV) at day 3 was inversely correlated with later antibody titers. Vaccination of CamkIV −/− mice with TIV induced enhanced antigen-specific antibody titers, demonstrating an unappreciated role for CaMKIV in the regulation of antibody responses. Thus systems approaches can predict immunogenicity, and reveal new mechanistic insights about vaccines.

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Author and article information

Journal

Journal ID (nlm-ta): Philos Trans R Soc Lond B Biol Sci

Journal ID (iso-abbrev): Philos. Trans. R. Soc. Lond., B, Biol. Sci

Journal ID (publisher-id): RSTB

Journal ID (hwp): royptb

Title: Philosophical Transactions of the Royal Society B: Biological Sciences

Publisher: The Royal Society

ISSN (Print): 0962-8436

ISSN (Electronic): 1471-2970

Publication date (Print): 19 June 2014

Publication date PMC-release: 19 June 2014

Volume: 369

Issue: 1645 , Theme Issue ‘After 2015: infectious diseases in a new era of health and development’ compiled and edited by Christopher Dye and Anne O'Garra

Electronic Location Identifier: 20130427

Affiliations

[1 ]Division of Immunoregulation, MRC National Institute for Medical Research , London NW7 1AA, UK

[2 ]Department of Respiratory Medicine, Imperial College Healthcare NHS Trust , St Mary's Hospital , London W2 1NY, UK

[3 ]NHLI, Faculty of Medicine, Imperial College London , London, UK

[4 ]Department of Respiratory Medicine, Royal Free London NHS Foundation Trust , London, UK

[5 ]Division of Medicine, University College London , London, UK

Author notes

e-mail: aogarra@ 123456nimr.mrc.ac.uk

One contribution of 12 to a Theme Issue ‘ After 2015: infectious diseases in a new era of health and development’.

Article

Publisher ID: rstb20130427

DOI: 10.1098/rstb.2013.0427

PMC ID: 4024221

PubMed ID: 24821914

SO-VID: b7a5d590-2c64-488a-8a52-73d1b422b275

License:

© 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.