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The plasma membrane is made up of lipids and proteins, and serves as an active interface between the cell and its environment. Many plasma-membrane proteins are laterally segregated in the plane of the membrane, but the underlying mechanisms remain controversial. Here we investigate the distribution and dynamics of a representative set of(More)
Osteosarcomas are aggressive bone tumours with a high degree of genetic heterogeneity, which has historically complicated driver gene discovery. Here we sequence exomes of 31 tumours and decipher their evolutionary landscape by inferring clonality of the individual mutation events. Exome findings are interpreted in the context of mutation and SNP array data(More)
MOTIVATION High-dimensional single-cell snapshot data are becoming widespread in the systems biology community, as a mean to understand biological processes at the cellular level. However, as temporal information is lost with such data, mathematical models have been limited to capture only static features of the underlying cellular mechanisms. RESULTS(More)
The identification of pathways pertinent to human diseases is critical for gaining a better understanding of their pathophysiology. Pathway knowledge in turn can provide disease marker information required for diagnosis, drug development and improved patient treatment. Psychiatric disorders including anxiety and depression are complex diseases and are(More)
Establishment of cell polarity--or symmetry breaking--relies on local accumulation of polarity regulators. Although simple positive feedback is sufficient to drive symmetry breaking, it is highly sensitive to stochastic fluctuations typical for living cells. Here, by integrating mathematical modelling with quantitative experimental validations, we show that(More)
TIRF microscopy has emerged as a powerful imaging technology to study spatio-temporal dynamics of fluorescent molecules in vitro and in living cells. The optical phenomenon of total internal reflection occurs when light passes from a medium with high refractive index into a medium with low refractive index at an angle larger than a characteristic critical(More)
How can we automatically spot all outstanding observations in a data set? This question arises in a large variety of applications, e.g. in economy, biology and medicine. Existing approaches to outlier detection suffer from one or more of the following drawbacks: The results of many methods strongly depend on suitable parameter settings being very difficult(More)
MicroRNAs are involved in almost all biological processes and have emerged as regulators of signaling pathways. We show that miRNA target genes and pathway genes are not uniformly expressed across human tissues. To capture tissue specific effects, we developed a novel methodology for tissue specific pathway analysis of miRNAs. We incorporated the most(More)
Modern high-throughput methods allow the investigation of biological functions across multiple 'omics' levels. Levels include mRNA and protein expression profiling as well as additional knowledge on, for example, DNA methylation and microRNA regulation. The reason for this interest in multi-omics is that actual cellular responses to different conditions are(More)