Transcription-based prediction of response to IFNbeta using supervised computational methods
Baranzini, Sergio E. (University of California, San Francisco)
Mousavi, Parvin (Queen's University, Kingston, Ontario)
Rio, Jordi (Hospital Universitari Vall d'Hebron)
Caillier, Stacy J. (University of California, San Francisco)
Stillman, Althea (University of California, San Francisco)
Villoslada, Pablo (Clínica Universidad de Navarra)
Wyatt, Mathew M. (University of California, San Francisco)
Comabella, Manuel (Hospital Universitari Vall d'Hebron)
Greller, Larry D. (Biosystemix, Sydenham, Ontario)
Somogyi, Roland (Biosystemix, Sydenham, Ontario)
Montalban, Xavier (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Oksenberg, Jorge (University of California, San Francisco)

Data:	2005
Descripció:	11 pàg.
Resum:	Changes in cellular functions in response to drug therapy are mediated by specific transcriptional profiles resulting from the induction or repression in the activity of a number of genes, thereby modifying the preexisting gene activity pattern of the drug-targeted cell(s). Recombinant human interferon beta (rIFNbeta) is routinely used to control exacerbations in multiple sclerosis patients with only partial success, mainly because of adverse effects and a relatively large proportion of nonresponders. We applied advanced data-mining and predictive modeling tools to a longitudinal 70-gene expression dataset generated by kinetic reverse-transcription PCR from 52 multiple sclerosis patients treated with rIFNbeta to discover higher-order predictive patterns associated with treatment outcome and to define the molecular footprint that rIFNbeta engraves on peripheral blood mononuclear cells. We identified nine sets of gene triplets whose expression, when tested before the initiation of therapy, can predict the response to interferon beta with up to 86% accuracy. In addition, time-series analysis revealed potential key players involved in a good or poor response to interferon beta. Statistical testing of a random outcome class and tolerance to noise was carried out to establish the robustness of the predictive models. Large-scale kinetic reverse-transcription PCR, coupled with advanced data-mining efforts, can effectively reveal preexisting and drug-induced gene expression signatures associated with therapeutic effects.
Nota:	Altres ajuts: National Institutes of Health grant 1RO1 AI42911; National Multiple Sclerosis Society; Wadsworth Foundation
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PLoS biology, Vol. 3 Núm. 1 (2005) , art. e2, ISSN 1545-7885

DOI: 10.1371/journal.pbio.0030002
PMID: 15630474
PMID: PMC539058

11 p, 711.9 KB

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