Abstract
Abstract In this study, we focus on investigating significant functional modules and signal pathways in differential process from human embryonic stem cells (hESCs) to dopamine (DA) neurons. By data integration and mining, we can construct a candidate protein-protein interaction (PPI) network for expansion and differentiation process of hESCs. Then, based on microarray data in three differentiation conditions of hESCs and dynamic model identification method, we could prune the false positive PPIs in candidate PPI network to obtain refined PPI networks in three differentiation processes of hESCs to the development of DA neurons. By comparing three refined PPI networks at three differentiation conditions, which represent three transition stages of differential PPI network in differentiation of hESCs to DA neurons, we obtain more realistic dynamic PPI networks as PPI network reconfiguration with significant PPI changes between three stages of differentiation process. Then enriched functional modules among these significant changes in differential PPI networks were investigated by Reactome annotation. Four noteworthy biological functions in hESCs differentiation, such as developmental biology, immune system, apotosis and hemostasis were found on important developmental mechanism of DA neuron from the perspective of differential PPI network. From these functional modules, we speculate that significant DA developmental pathways, like Angiogenesis, TGF-beta signaling pathway, PI3 kinase pathway, Wnt signaling pathway, can provide more insights into the molecular mechanisms of differentiation. The proposed differential PPI network scheme can provide useful strategies for medical therapy and facilitate the development of new drug targets for Parkinson's disease.