BACKGROUND: A number of software packages are available to generate DNA multiple sequence alignments (MSAs) evolved under continuous-time Markov processes on phylogenetic trees. On the other hand, methods of simulating the DNA MSA directly from the transition matrices do not exist. Moreover, existing software restricts to the time-reversible models and it is not optimized to generate nonhomogeneous data (i.e. placing distinct substitution rates at different lineages). RESULTS: We present the first package designed to generate MSAs evolving under discrete-time Markov processes on phylogenetic trees, directly from probability substitution matrices. Based on the input model and a phylogenetic tree in the Newick format (with branch lengths measured as the expected number of substitutions per site), the algorithm produces DNA alignments of desired length. GenNon-h is publicly available for download. CONCLUSION: The software presented here is an efficient tool to generate DNA MSAs on a given phylogenetic tree. GenNon-h provides the user with the nonstationary or nonhomogeneous phylogenetic data that is well suited for testing complex biological hypotheses, exploring the limits of the reconstruction algorithms and their robustness to such models.

MOTIVATION: Genome-scale 'omics' data constitute a potentially rich source of information about biological systems and their function. There is a plethora of tools and methods available to mine omics data. However, the diversity and complexity of different omics data types is a stumbling block for multi-data integration, hence there is a dire need for additional methods to exploit potential synergy from integrated orthogonal data. Rough Sets provide an efficient means to use complex information in classification approaches. Here, we set out to explore the possibilities of Rough Sets to incorporate diverse information sources in a functional classification of unknown genes. RESULTS: We explored the use of Rough Sets for a novel data integration strategy where gene expression data, protein features and Gene Ontology (GO) annotations were combined to describe general and biologically relevant patterns represented by If-Then rules. The descriptive rules were used to predict the function of unknown genes in Arabidopsis thaliana and Schizosaccharomyces pombe. The If-Then rule models showed success rates of up to 0.89 (discriminative and predictive power for both modeled organisms); whereas, models built solely of one data type (protein features or gene expression data) yielded success rates varying from 0.68 to 0.78. Our models were applied to generate classifications for many unknown genes, of which a sizeable number were confirmed either by PubMed literature reports or electronically interfered annotations. Finally, we studied cell cycle protein-protein interactions derived from both tandem affinity purification experiments and in silico experiments in the BioGRID interactome database and found strong experimental evidence for the predictions generated by our models. The results show that our approach can be used to build very robust models that create synergy from integrating gene expression data and protein features. AVAILABILITY: The Rough Set-based method is implemented in the Rosetta toolkit kernel version 1.0.1 available at: http://rosetta.lcb.uu.se/