Motivation: Biclustering of transcriptomic data groups genes and samples simultaneously. It is emerging as a standard tool for extracting knowledge from gene expression measurements. We propose a novel generative approach for biclustering called ‘FABIA: Factor Analysis for Bicluster Acquisition’. FABIA is based on a multiplicative model, which accounts for linear dependencies between gene expression and conditions, and also captures heavy-tailed distributions as observed in real-world transcriptomic data. The generative framework allows to utilize well-founded model selection methods and to apply Bayesian techniques.Results: On 100 simulated datasets with known true, artificially implanted biclusters, FABIA clearly outperformed all 11 competitors. On these datasets, FABIA was able to separate spurious biclusters from true biclusters by ranking biclusters according to their information content. FABIA was tested on three microarray datasets with known subclusters, where it was two times the best and once the second best method among the compared biclustering approaches.Availability: FABIA is available as an R package on Bioconductor (http://www.bioconductor.org). All datasets, results and software are available at http://www.bioinf.jku.at/software/fabia/fabia.htmlContact: hochreit@bioinf.jku.atSupplementary information: Supplementary data are available at Bioinformatics online.
Conclusions:The potent antitumor activity as a single agent in preclinical models combined with its favorable pharmacodynamic profile makes JNJ-26481585 a promising "second-generation" HDAC inhibitor. The compound is currently in clinical studies, to evaluate its potential applicability in a broad spectrum of both solid and hematologic malignancies. (Clin Cancer Res 2009;15(22):6841-51)
Evolutionary studies typically focus on adaptations to particular environmental conditions, thereby often ignoring the role of possible constraints. Here we focus on the case of variation in dorsal wing melanization in a satyrine butterfly Pararge aegeria. Because melanin is a complex polymer, its synthesis may be constrained if ambient conditions limit the resource budget. This hypothesis was tested by comparing melanization among butterflies that fed as larvae on host grasses experiencing different drought-stress treatments. Treatment differences were validated both at the level of the host plant (nitrogen, carbonate, and water content) and of the butterfly (life-history traits: survival, development time, and size at maturity). Melanization rate was measured as average gray value of the basal dorsal wing area. This area, close to the thorax, is known to be functionally significant for basking in order to thermoregulate. Individuals reared on drought-stressed host plants developed paler wings, and development of darker individuals was slower and less stable as estimated by their level of fluctuating asymmetry. These results provide evidence that melanin is indeed costly to synthesize, and that differences in environmental quality can induce phenotypic variation in wing melanization. Therefore, studies dealing with spatial and/or temporal patterns of variation in wing melanization should not focus on adaptive explanations alone, but rather on a cost-benefit balance under particular sets of environmental conditions.
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