UNLABELLED: Understanding the effect of single nucleotide polymorphisms (SNPs) on the expression level of genes is an important goal. We recently published a study in which we devised a multi-SNP predictive model for gene expression in Lymphoblastoid cell lines (LCL), and showed that it can robustly predict the expression of a small number of genes in test individuals. Here, we validate the generality of our models by predicting expression profiles for genes in LCL in an independent study, and extend the pool of predictable genes for which we are able to explain more than 25% of their expression variability to 232 genes across 14 different cell types. As the number of people who obtained their SNP profiles through companies such as 23andMe is rising rapidly, we developed GenoExp, a web-based tool in which users can upload their individual SNP data and obtain predicted expression levels for the set of predictable genes across the 14 different cell types. Our tool thus allows users with biological knowledge to study the possible effects that their set of SNPs might have on these genes and predict their cell-specific expression levels relative to the population average. AVAILABILITY AND IMPLEMENTATION: GenoExp is freely available at http://genie.weizmann.ac.il/pubs/GenoExp/.

Genome-wide association studies (GWAS) are widely used to search for genetic loci that underlie human disease. Another goal is to predict disease risk for different individuals given their genetic sequence. Such predictions could either be used as a "black box" in order to promote changes in life-style and screening for early diagnosis, or as a model that can be studied to better understand the mechanism of the disease. Current methods for risk prediction typically rank single nucleotide polymorphisms (SNPs) by the p-value of their association with the disease, and use the top-associated SNPs as input to a classification algorithm. However, the predictive power of such methods is relatively poor. To improve the predictive power, we devised BootRank, which uses bootstrapping in order to obtain a robust prioritization of SNPs for use in predictive models. We show that BootRank improves the ability to predict disease risk of unseen individuals in the Wellcome Trust Case Control Consortium (WTCCC) data and results in a more robust set of SNPs and a larger number of enriched pathways being associated with the different diseases. Finally, we show that combining BootRank with seven different classification algorithms improves performance compared to previous studies that used the WTCCC data. Notably, diseases for which BootRank results in the largest improvements were recently shown to have more heritability than previously thought, likely due to contributions from variants with low minimum allele frequency (MAF), suggesting that BootRank can be beneficial in cases where SNPs affecting the disease are poorly tagged or have low MAF. Overall, our results show that improving disease risk prediction from genotypic information may be a tangible goal, with potential implications for personalized disease screening and treatment.