The network properties of myelodysplastic syndromes pathogenesis revealed by an integrative systems biological method

Insight into the molecular mechanism of complex diseases is an important topic in the current bio-medical research. However, different from the single-gene disorders, high heterogeneity of many of the complex diseases prevents scientists from the exact understanding of the etiology. In this study, we used Myelodysplastic Syndromes (MDSs), a heterogeneous family of clonal disorders of hematopoietic stem cells, as a general model to explore the network properties of the heterogeneity of complex diseases. First, static bioinformatics analysis suggests that despite the huge heterogeneity of MDSs, their clinical properties can be explained well by the local properties of MDS-related genes on the human interactome. Then we design a novel systems biological method to explore the pattern of genetic abnormality propagation of a real MDS cohort by integrating flowcytometry, genotyping, gene expression profiling, expression quantitative trait loci (eQTLs) mapping and pathway inference. We constructed a MDS disease gene network which suggests the network basis of the heterogeneity of MDSs. The pipeline we proposed and the implication the results suggest may be helpful in the research of other complex diseases.