Comput Methods Programs Biomed - OLYMPUS: an automated hybrid clustering method in time series gene expression. Case study: host response after Influenza A (H1N1) infection.

Tópicos

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Resumo

The increasing flow of short time series microarray experiments for the study of dynamic cellular processes poses the need for efficient clustering tools. These tools must deal with three primary issues: first, to consider the multi-functionality of genes; second, to evaluate the similarity of the relative change of amplitude in the time domain rather than the absolute values; third, to cope with the constraints of conventional clustering algorithms such as the assignment of the appropriate cluster number. To address these, we propose OLYMPUS, a novel unsupervised clustering algorithm that integrates Differential Evolution (DE) method into Fuzzy Short Time Series (FSTS) algorithm with the scope to utilize efficiently the information of population of the first and enhance the performance of the latter. Our hybrid approach provides sets of genes that enable the deciphering of distinct phases in dynamic cellular processes. We proved the efficiency of OLYMPUS on synthetic as well as on experimental data. The discriminative power of OLYMPUS provided clusters, which refined the so far perspective of the dynamics of host response mechanisms to Influenza A (H1N1). Our kinetic model sets a timeline for several pathways and cell populations, implicated to participate in host response; yet no timeline was assigned to them (e.g. cell cycle, homeostasis). Regarding the activity of B cells, our approach revealed that some antibody-related mechanisms remain activated until day 60 post infection. The Matlab codes for implementing OLYMPUS, as well as example datasets, are freely accessible via the Web (http://biosignal.med.upatras.gr/wordpress/biosignal/).

Resumo Limpo

increas flow short time seri microarray experi studi dynam cellular process pose need effici cluster tool tool must deal three primari issu first consid multifunct gene second evalu similar relat chang amplitud time domain rather absolut valu third cope constraint convent cluster algorithm assign appropri cluster number address propos olympus novel unsupervis cluster algorithm integr differenti evolut de method fuzzi short time seri fsts algorithm scope util effici inform popul first enhanc perform latter hybrid approach provid set gene enabl deciph distinct phase dynam cellular process prove effici olympus synthet well experiment data discrimin power olympus provid cluster refin far perspect dynam host respons mechan influenza hn kinet model set timelin sever pathway cell popul implic particip host respons yet timelin assign eg cell cycl homeostasi regard activ b cell approach reveal antibodyrel mechan remain activ day post infect matlab code implement olympus well exampl dataset freeli access via web httpbiosignalmedupatrasgrwordpressbiosign

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