Abstract:The integration of multi-dimensional 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. However, the large amount of data adds burden to any inference task. Flexible Bayesian methods may reduce the necessity for strong modelling assumptions, but can also increase the computational burden. We present an improved implementation of a Bayesian correlated clustering algorithm, that permits integrated clustering to be routinely performed across multiple datasets, each with tens of thousands of items. By exploiting GPU based computation, we are able to improve runtime performance of the algorithm by almost four orders of magnitude. This permits analysis across genomic-scale data sets, greatly expanding the range of applications over those originally possible. MDI is available here:

Spatial effects such as cell shape have very often been considered negligible in models of cellular pathways, and many existing simulation infrastructures do not take such effects into consideration. Recent experimental results are reversing this judgement by showing that very small spatial variations can make a big difference in the fate of a cell. This is particularly the case when considering eukaryotic cells, which have a complex physical structure and many subtle control mechanisms, but bacteria are also interesting for the huge variation in shape both between species and in different phases of their lifecycle. In this work we perform simulations that measure the effect of three common bacterial shapes on the behaviour of model cellular pathways. To perform these experiments we develop ReDi-Cell, a highly scalable GPGPU cell simulation infrastructure for the modelling of cellular pathways in spatially detailed environments. ReDi-Cell is validated against known-good simulations, prior to its use in new work. We then use ReDi-Cell to conduct novel experiments that demonstrate the effect that three common bacterial shapes (Cocci, Bacilli and Spirilli) have on the behaviour of model cellular pathways. Pathway wavefront shape, pathway concentration gradients, and chemical species distribution are measured in the three different shapes. We also quantify the impact of internal cellular clutter on the same pathways. Through this work we show that variations in the shape or configuration of these common cell shapes alter model cell behaviour.