Outline of the work flow employed to identify network-central disease DEGs.

Each DEG (differentially expressed gene) is mapped to unique protein using STRING database. (A) We obtain time-specific protein functional networks (Ni) by mapping the timestamped DEGs (Di) to functional PPI networks from STRING database. We then combine network central DEGs (Si) for each time-specific networks to obtain network central DEGs corresponding to a particular mouse strain-prion strain combination (CNDi). Finally, we combine all the CNDs to identify 148 DEGs which are common to atleast 4 mouse strain-prion strain combinations. (B) We compare each time-specific protein network (Ni) corresponding to any of the 5 disease developing mouse-prion models with the network DEGs of the control combination. We identify two sets of DEGs. First set consists of the DEGs (TUDs) which are unique at a particular time-stamp and also present as hubs in the given DEGs network. Second set consists of the DEGs (TDCDs) which are common to both the diseased and control combinations but has relatively high centrality measures in diseased network compared to any of the time-specific networks corresponding to the control combination. Finally, we combine these two sets to give time specific network central DEGs (TNDs/Si) for each of the disease related protein networks.