Bayesian correlated clustering to integrate multiple datasets.

MOTIVATION: The integration of multiple datasets remains a key challenge in systems biology and genomic medicine. Modern high-throughput technologies generate a broad array of different data types, providing distinct-but often complementary-information. We present a Bayesian method for the unsupervised integrative modelling of multiple datasets, which we refer to as MDI (Multiple Dataset Integration). MDI can integrate information from a wide range of different datasets and data types simultaneously (including the ability to model time series data explicitly using Gaussian processes). Each dataset is modelled using a Dirichlet-multinomial allocation (DMA) mixture model, with dependencies between these models captured through parameters that describe the agreement among the datasets. RESULTS: Using a set of six artificially constructed time series datasets, we show that MDI is able to integrate a significant number of datasets simultaneously, and that it successfully captures the underlying structural similarity between the datasets. We also analyse a variety of real Saccharomyces cerevisiae datasets. In the two-dataset case, we show that MDI's performance is comparable with the present state-of-the-art. We then move beyond the capabilities of current approaches and integrate gene expression, chromatin immunoprecipitation-chip and protein-protein interaction data, to identify a set of protein complexes for which genes are co-regulated during the cell cycle. Comparisons to other unsupervised data integration techniques-as well as to non-integrative approaches-demonstrate that MDI is competitive, while also providing information that would be difficult or impossible to extract using other methods.

Competitive performance as a discriminator of doping status in elite athletes.

As the aim of any doping regime is to improve sporting performance, it has been suggested that analysis of athlete competitive results might be informative in identifying those at greater risk of doping. This research study aimed to investigate the utility of a statistical performance model to discriminate between athletes who have a previous anti-doping rule violation (ADRV) and those who do not. We analysed performances of male and female 100 and 800 m runners obtained from the World Athletics database using a Bayesian spline model. Measures of unusual improvement in performance were quantified by comparing the yearly change in athlete's performance (delta excess performance) to quantiles of performance in their age-matched peers from the database population. The discriminative ability of these measures was investigated using the area under the ROC curve (AUC) with the 55%, 75% and 90% quantiles of the population performance. The highest AUC values across age were identified for the model with a 75% quantile (AUC = 0.78-0.80). The results of this study demonstrate that delta excess performance was able to discriminate between athletes with and without ADRVs and therefore could be used to assist in the risk stratification of athletes for anti-doping purposes.

Discovering transcriptional modules by Bayesian data integration.

MOTIVATION: We present a method for directly inferring transcriptional modules (TMs) by integrating gene expression and transcription factor binding (ChIP-chip) data. Our model extends a hierarchical Dirichlet process mixture model to allow data fusion on a gene-by-gene basis. This encodes the intuition that co-expression and co-regulation are not necessarily equivalent and hence we do not expect all genes to group similarly in both datasets. In particular, it allows us to identify the subset of genes that share the same structure of transcriptional modules in both datasets. RESULTS: We find that by working on a gene-by-gene basis, our model is able to extract clusters with greater functional coherence than existing methods. By combining gene expression and transcription factor binding (ChIP-chip) data in this way, we are better able to determine the groups of genes that are most likely to represent underlying TMs. AVAILABILITY: If interested in the code for the work presented in this article, please contact the authors. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.