Institute of Plant Science, ETH Zurich, Universitaetsstr, 2, 8092 Zurich, Switzerland- dhs@ethz-ch
Abstract: BACKGROUND- Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes- Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target- Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size- RESULTS- We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process- To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity- Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens- Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups- The approach identifies a small group of genes as candidates involved in spindle migration- Experimental testing confirms the majority of our candidates and we present she1 -YBL031W- as a novel gene involved in spindle migration- We applied the statistical methodology also to TOR2 signaling as another example- CONCLUSION- We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets- For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process-