A system and method for identification of key driver responsible for bringing changes in a microbial population is provided. The method involves construction of microbial association networks with each microbial taxa as nodes and their associations as edges and subsequent identification of crucial ‘driver’ nodes involved in the studied disease progression. While comparing a particular node between two networks, this method takes individual nodes and their associations into account as well as the identity of their interacting partners. A taxon in the diseased state with an altered set of associations while still being increasingly important for the whole network necessarily holds a key significance in microbial interplay. Using this rationale, this methodology computes a score to quantify this change for each node and calculates its statistical significance. Subsequently, ‘driver’ nodes are identified using the score coupled with other network parameters and a critical score for the ‘driver’ nodes is calculated to quantify its importance.