GeneFriends: An RNA-seq co-expression tool for functional annotation and candidate gene prioritization

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Over the past decade, and in part thanks to the sequencing of the human genome, research in the field of genetics has rapidly expanded leading to the identification of many genes associated with multiple human diseases and traits. Even though science has gained a broader understanding of most human diseases, many unanswered questions remain and the genetic basis of the majority of human common diseases and most human traits is only partly understood. This project aims to construct a new online tool to help researchers infer the functions of unknown genes as well as identify candidate new players for roles in diseases and in biological processes. This tool will be based on data obtained from the state-of-the-art RNA sequencing technology (RNA-seq). This technology allows researchers to measure the activity of genes in a given sample with greater accuracy than previous methods and is capable of measuring genes that to not encode proteins. A growing number of researchers currently employ RNA-seq, yet many genes associated with diseases and processes have unknown functions, which impedes understanding the mechanisms involved. To address this issue, our proposed tool, entitled GeneFriends, employs a guilt-by-association methodology to the analysis of genes. This approach identifies which genes tend to be activated simultaneously across multiple samples. Based on the idea that genes that are activated at the same time are functionally related, it is possible to predict the functions of previously unstudied genes based on the functions of the known genes they are co-activated with. To determine how genes tend to be co-activated, thousands of publicly available samples of previously measured gene levels using RNA-seq will be combined. This way a map will be generated that describes which genes generally tend to act together. GeneFriends will allow scientists and clinicians to infer the function of unknown genes. Additionally, GeneFriends can be used to associate new genes with diseases and processes based on the fact that they were active at the same time as other genes previously identified as important for that disease or process. The corresponding tool created in this project will then allow researchers to relate new factors to diseases, identify candidate drug targets, potentially leading to new types of diagnosis and treatments. GeneFriends will be initially created for humans and mice and will be made freely available online for researchers, clinicians and commercial companies to use.