Inference of functional association networks and gene orthology

Sammanfattning: Most proteomics and genomics experiments are performed on a small set of well-studied model organisms and their results are generalized to other species. This is possible because all species are evolutionarily related. When transferring information across species, orthologs are the most likely candidates for functional equivalence. The InParanoid algorithm, which predicts orthology relations by sequence similarity based clustering, was improved by increasing its robustness for low complexity sequences and the corresponding database was updated to include more species.A plethora of different orthology inference methods exist, each featuring different formats. We have addressed the great need for standardization this creates with the development of SeqXML and OrthoXML, two formats that standardize the input and output of ortholog inference.Essentially all biological processes are the result of a complex interplay between different biomolecules. To fully understand the function of genes or gene products one needs to identify these relations. Integration of different types of high-throughput data allows the construction of genome-wide functional association networks that give a global picture of the relation landscape.FunCoup is a framework that performs this integration to create functional association networks for 11 model organisms. Orthology assignments from InParanoid are used to transfer high-throughput data between species, which contributes with more than 50% to the total functional association evidence. We have developed procedures to incorporate new evidence types, improved the procedures of existing evidence types, created networks for additional species, and added significantly more data. Furthermore, the integration procedure was improved to account for data redundancy and to increase its overall robustness. Many of these changes were possible because the computational framework was re-implemented from scratch.