Brief. Bioinformatics - Learning transcriptional regulation on a genome scale: a theoretical analysis based on gene expression data.

Tópicos

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Resumo

The recent advent of high-throughput microarray data has enabled the global analysis of the transcriptome, driving the development and application of computational approaches to study transcriptional regulation on the genome scale, by reconstructing in silico the regulatory interactions of the gene network. Although there are many in-depth reviews of such 'reverse-engineering' methodologies, most have focused on the practical aspect of data mining, and few on the biological problem and the biological relevance of the methodology. Therefore, in this review, from a biological perspective, we used a set of yeast microarray data as a working example, to evaluate the fundamental assumptions implicit in associating transcription factor (TF)-target gene expression levels and estimating TFs' activity, and further explore cooperative models. Finally we confirm that the detailed transcription mechanism is overly-complex for expression data alone to reveal, nevertheless, future network reconstruction studies could benefit from the incorporation of context-specific information, the modeling of multiple layers of regulation (e.g. micro-RNA), or the development of approaches for context-dependent analysis, to uncover the mechanisms of gene regulation.

Resumo Limpo

recent advent highthroughput microarray data enabl global analysi transcriptom drive develop applic comput approach studi transcript regul genom scale reconstruct silico regulatori interact gene network although mani indepth review reverseengin methodolog focus practic aspect data mine biolog problem biolog relev methodolog therefor review biolog perspect use set yeast microarray data work exampl evalu fundament assumpt implicit associ transcript factor tftarget gene express level estim tfs activ explor cooper model final confirm detail transcript mechan overlycomplex express data alon reveal nevertheless futur network reconstruct studi benefit incorpor contextspecif inform model multipl layer regul eg microrna develop approach contextdepend analysi uncov mechan gene regul

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