BiTrinA--multiscale binarization and trinarization with quality analysis.

MOTIVATION: When processing gene expression profiles or other biological data, it is often required to assign measurements to distinct categories (e.g. 'high' and 'low' and possibly 'intermediate'). Subsequent analyses strongly depend on the results of this quantization. Poor quantization will have potentially misleading effects on further investigations. We propose the BiTrinA package that integrates different multiscale algorithms for binarization and for trinarization of one-dimensional data with methods for quality assessment and visualization of the results. By identifying measurements that show large variations over different time points or conditions, this quality assessment can determine candidates that are related to the specific experimental setting. AVAILABILITY AND IMPLEMENTATION: BiTrinA is freely available on CRAN. CONTACT: hans.kestler@leibniz-fli.de or hans.kestler@uni-ulm.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BoolNet--an R package for generation, reconstruction and analysis of Boolean networks.

MOTIVATION: As the study of information processing in living cells moves from individual pathways to complex regulatory networks, mathematical models and simulation become indispensable tools for analyzing the complex behavior of such networks and can provide deep insights into the functioning of cells. The dynamics of gene expression, for example, can be modeled with Boolean networks (BNs). These are mathematical models of low complexity, but have the advantage of being able to capture essential properties of gene-regulatory networks. However, current implementations of BNs only focus on different sub-aspects of this model and do not allow for a seamless integration into existing preprocessing pipelines. RESULTS: BoolNet efficiently integrates methods for synchronous, asynchronous and probabilistic BNs. This includes reconstructing networks from time series, generating random networks, robustness analysis via perturbation, Markov chain simulations, and identification and visualization of attractors. AVAILABILITY: The package BoolNet is freely available from the R project at http://cran.r-project.org/ or http://www.informatik.uni-ulm.de/ni/mitarbeiter/HKestler/boolnet/ under Artistic License 2.0. CONTACT: hans.kestler@uni-ulm.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Multiscale binarization of gene expression data for reconstructing Boolean networks.

Network inference algorithms can assist life scientists in unraveling gene-regulatory systems on a molecular level. In recent years, great attention has been drawn to the reconstruction of Boolean networks from time series. These need to be binarized, as such networks model genes as binary variables (either "expressed" or "not expressed"). Common binarization methods often cluster measurements or separate them according to statistical or information theoretic characteristics and may require many data points to determine a robust threshold. Yet, time series measurements frequently comprise only a small number of samples. To overcome this limitation, we propose a binarization that incorporates measurements at multiple resolutions. We introduce two such binarization approaches which determine thresholds based on limited numbers of samples and additionally provide a measure of threshold validity. Thus, network reconstruction and further analysis can be restricted to genes with meaningful thresholds. This reduces the complexity of network inference. The performance of our binarization algorithms was evaluated in network reconstruction experiments using artificial data as well as real-world yeast expression time series. The new approaches yield considerably improved correct network identification rates compared to other binarization techniques by effectively reducing the amount of candidate networks.