Highlight talk – Theme: Systems
Abstract
Genes display epistatic (genetic) interactions, whereby the presence of one genetic variant can mask, alleviate or amplify the phenotypic effect of other variants. Such a directional relationship is present, for instance, if one gene product positively or negatively regulates the activity of the other, if its function temporally precedes that of the other. Here, we present a method that combines genetic interactions on multiple phenotypes to reveal directional relationships, and report a dense regulatory network covering 1367 genes. It reveals the directional, temporal and logical relationships between genes and allows us to dissect regulatory networks using high-throughput intervention experimentation. The network could reconstruct the sequence of protein activities in mitosis, and revealed that the Ras pathway interacts with the SWI/SNF chromatin-remodelling complex. Our work presents a powerful approach for reconstructing directional regulatory networks, and provides a resource for the interpretation of functional consequences of genomic alterations in disease.
Authors
Bernd Fischer, DKFZ, Germany
Thomas Sandmann, DKFZ, Germany
Thomas Horn, DKFZ, Germany
Maximilian Billmann, DKFZ, Germany
Varun Chaudhary, DKFZ, Germany
Wolfgang Huber, EMBL, Germany
Michael Boutros, DKFZ, Germany