Identifying biological response pathways

Abstract

A method for operating a machine for identifying a mechanism associated with a cellular response includes identifying molecules participating in the cellular response, accessing a database containing information characterizing molecular interactions, determining pathways connecting the identified molecules participating in the response, and solving an optimization problem. The pathways comprise nodes, each representing a molecule, and edges, each connecting a pair of nodes and representing an interaction between a respective pair of molecules represented by the pair of nodes. The nodes includes a subset that represent molecules identified as participating in the cellular response. Solving an optimization problem comprises determining a subset of the molecules and interactions having a minimum aggregate cost, associating each participating node with a penalty value, associating each edge with a cost value, forming an objective function based on the penalty and cost values, and identifying the sub-network of nodes and edges that minimizes the objective function.

Having described the invention, and a preferred embodiment thereof, what is claimed as new and secured by Letters Patent is: 
     
         1 . A method for operating a machine for identifying a mechanism associated with a cellular response with the aid of a digital computer, said method comprising identifying molecules participating in said cellular response, causing said computer to access a database containing information characterizing molecular interactions, causing said computer to determine pathways connecting said identified molecules participating in said cellular response, and causing said computer to solve an optimization problem, wherein said pathways comprise a plurality of nodes, each node representing a molecule, and a plurality of edges, each edge connecting a respective pair of nodes and representing an interaction between a respective pair of molecules represented by the respective pair of nodes, wherein said plurality of nodes includes a subset of nodes that represent molecules identified as participating in the cellular response, and wherein causing said computer to solve an optimization problem comprises determining a subset of the molecules and interactions having a minimum aggregate cost, associating each node that participates in the cellular response with a penalty value, associating each edge with a cost value, forming an objective function based on the penalty values and the cost values, and identifying the sub-network of nodes and edges that minimizes a value of the objective function. 
     
     
         2 . The method of  claim 1 , wherein said pathways further include one or more intermediate nodes between said nodes participating in said cellular response 
     
     
         3 . The method of  claim 1 , wherein causing said computer to determine pathways connecting said identified molecules participating in said cellular response includes numerically processing data representing said network of potential interactions to determine a sub-network of nodes and edges representative of a response pathway between said input and said output. 
     
     
         4 . The method of  claim 1 , wherein identifying molecules participating in a cellular response comprises identifying phosphorylated proteins. 
     
     
         5 . The method of  claim 1 , wherein identifying molecules participating in a cellular response comprises identifying proteins encoded by a gene that, when deleted, causes a change in an organism's phenotype. 
     
     
         6 . The method of  claim 1 , wherein identifying molecules participating in a cellular response comprises identifying proteins that are present in an amount that changes during a cellular response. 
     
     
         7 . The method of  claim 1 , wherein identifying molecules participating in said cellular response comprises identifying proteins. 
     
     
         8 . The method of  claim 1 , wherein identifying molecules participating in said cellular response comprises identifying mRNAs. 
     
     
         9 . The method of  claim 1 , wherein identifying molecules participating in said cellular response comprises identifying DNA sequences. 
     
     
         10 . The method of  claim 1 , wherein identifying molecules participating in said cellular response comprises identifying protein-protein complexes. 
     
     
         11 . The method of  claim 1 , wherein each edge is associated with a value that represents a degree of interaction between respective molecules represented by said pair of nodes connected by said edge. 
     
     
         12 . The method of  claim 1 , wherein said cellular response is a signaling event. 
     
     
         13 . The method of  claim 1 , wherein said cellular response is a metabolic event. 
     
     
         14 . The method of  claim 1 , wherein said cellular response is a phenotypic response to a stimulus.