Abstract

BackgroundThe ability to monitor changes in expression patterns over time, and to observe the emergence of coherent temporal responses using expression time series, is critical to advance our understanding of complex biological processes. Biclustering has been recognized as an effective method for discovering local temporal expression patterns and unraveling potential regulatory mechanisms. The general biclustering problem is NP-hard. In the case of time series this problem is tractable, and efficient algorithms can be used. However, there is still a need for specialized applications able to take advantage of the temporal properties inherent to expression time series, both from a computational and a biological perspective.FindingsBiGGEsTS makes available state-of-the-art biclustering algorithms for analyzing expression time series. Gene Ontology (GO) annotations are used to assess the biological relevance of the biclusters. Methods for preprocessing expression time series and post-processing results are also included. The analysis is additionally supported by a visualization module capable of displaying informative representations of the data, including heatmaps, dendrograms, expression charts and graphs of enriched GO terms.ConclusionBiGGEsTS is a free open source graphical software tool for revealing local coexpression of genes in specific intervals of time, while integrating meaningful information on gene annotations. It is freely available at: . We present a case study on the discovery of transcriptional regulatory modules in the response of Saccharomyces cerevisiae to heat stress.

Highlights

  • The ability to monitor changes in expression patterns over time, and to observe the emergence of coherent temporal responses using expression time series, is critical to advance our understanding of complex biological processes

  • We present a case study on the discovery of transcriptional regulatory modules in the response of Saccharomyces cerevisiae to heat stress

  • Main functionalities are directly selected in the tabs and guide the researcher through a complete process of analysis: 1) input and preprocessing of expression data, 2) identification of coexpressed genes in specific subsets of time points using biclustering, 3) post-processing of biclusters in order to rank the results, 4) usage of exploratory analysis tools

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Summary

Conclusion

BiGGEsTS is a software for analyzing gene expression time series using biclustering. It was designed to comply with the broad specifications of a software tool, essentially focused on user-friendliness, platform independence, modularity, reusability and efficiency. The latter are suitable for highlighting the coherent behavior of the genes in the bicluster time points as opposed to the uncorrelated behavior in the remaining time points Both expression and pattern charts provide a context menu with extra functionalities, including displaying and modifying chart properties, saving chart to an image file, printing, and zooming in or out. EFxigpurersesi3on matrix, heatmaps, GO annotations, and dendrograms Expression matrix, heatmaps, GO annotations, and dendrograms We show: (a) tables of values, (b) tables of colors, (c) tables of symbols, (d) list of GO terms annotating a gene, and (e) dendrograms. Each remaining cell in the table contains the expression value of a given gene in a specific condition. Arrows define specialization relations: each arrow goes from a more general term to its specialization(s)

Background
Methods
23. Madeira SC
25. Saldanha AJ
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