Clinical bioinformatics for complex disorders: a schizophrenia case study

BACKGROUND: In the diagnosis of complex diseases such as neurological pathologies, a wealth of clinical and molecular information is often available to help the interpretation. Yet, the pieces of information are usually considered in isolation and rarely integrated due to the lack of a sound statistical framework. This lack of integration results in the loss of valuable information about how disease associated factors act synergistically to cause the complex phenotype. RESULTS: Here, we investigated complex psychiatric diseases as networks. The networks were used to integrate data originating from different profiling platforms. The weighted links in these networks capture the association between the analyzed factors and allow the quantification of their relevance for the pathology. The heterogeneity of the patient population was analyzed by clustering and graph theoretical procedures. We provided an estimate of the heterogeneity of the population of schizophrenia and detected a subgroup of patients featuring remarkable abnormalities in a network of serum primary fatty acid amides. We compared the stability of this molecular network in an extended dataset between schizophrenia and affective disorder patients and found more stable structures in the latter. CONCLUSION: We quantified robust associations between analytes measured with different profiling platforms as networks. The methodology allows the quantitative evaluation of the complexity of the disease. The identified disease patterns can then be further investigated with regards to their diagnostic utility or help in the prediction of novel therapeutic targets. The applied framework is able to enhance the understanding of complex psychiatric diseases, and may give novel insights into drug development and personalized medicine approaches.