A critical component for the success of the pathway-based analysis is the availability of a comprehensive collection of relevant gene sets related to the disease/genetic trait of interest. Current understanding of gene functions and pathways is still very limited. This is especially the case for neuropsychiatric diseases, as most of the gene sets currently available were generated based on experiments done on tumor cell lines. As a consequence, we have only limited knowledge regarding the pathways involved in brain development, and normal and pathological activities. In this regard, the pathways discovered by SSEA for schizophrenia are likely to be substantially incomplete. We expect the performance would improve as better and more comprehensive disease-related pathways become available. A future challenge is to curate pathways and gene sets in a disease specific way, possibly by taking advantage of the high-throughput functional genomics tools.
