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Title: A divisive Shuffling Approach (VIStA) for gene expression analysis to identify subtypes in Chronic Obstructive Pulmonary Disease
Author: Menche, Jörg
Sharma, Amitabh
Cho, Michael H.
Mayer, Ruth J.
Rennard, Stephen I.
Celli, Bartolome R.
Miller, Bruce E.
Locantore, Nicholas
Tal-Singer, Ruth
Ghosh, Soumitra
Larminie, Chris
Bradley, Glyn
Riley, John H.
Agustí García-Navarro, Àlvar
Silverman, Edwin K.
Barabási, Albert László
Keywords: Malalties pulmonars obstructives cròniques
Expressió gènica
Assaigs clínics
Chronic obstructive pulmonary diseases
Gene expression
Clinical trials
Issue Date: 13-Mar-2014
Publisher: BioMed Central
Abstract: An important step toward understanding the biological mechanisms underlying a complex disease is a refined understanding of its clinical heterogeneity. Relating clinical and molecular differences may allow us to define more specific subtypes of patients that respond differently to therapeutic interventions. Results We developed a novel unbiased method called diVIsive Shuffling Approach (VIStA) that identifies subgroups of patients by maximizing the difference in their gene expression patterns. We tested our algorithm on 140 subjects with Chronic Obstructive Pulmonary Disease (COPD) and found four distinct, biologically and clinically meaningful combinations of clinical characteristics that are associated with large gene expression differences. The dominant characteristic in these combinations was the severity of airflow limitation. Other frequently identified measures included emphysema, fibrinogen levels, phlegm, BMI and age. A pathway analysis of the differentially expressed genes in the identified subtypes suggests that VIStA is capable of capturing specific molecular signatures within in each group. Conclusions The introduced methodology allowed us to identify combinations of clinical characteristics that correspond to clear gene expression differences. The resulting subtypes for COPD contribute to a better understanding of its heterogeneity.
Note: Reproducció del document publicat a:
It is part of: BMC Systems Biology, 2014, vol. 8, num. Suppl 2, p. S8
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ISSN: 1752-0509
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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