Method for quantifying amplitude of a response of a biological network

Abstract

One or more measurement signatures are derived from a knowledge base of casual biological facts, where a signature is a collection of measured node entities and their expected directions of change with respect to a reference node. The knowledge base may be a directed network of experimentally-observed casual relationships among biological entities and processes, and a reference node represents a perturbation. A degree of activation of a signature is then assessed by scoring one or more “differential” data sets against the signature to compute an amplitude score. The amplitude score quantifies fold-changes of measurements in the signature. In one particular embodiment, the amplitude score is a weighted average of adjusted log-fold changes of measured node entities in the signature, wherein an adjustment applied to the log-fold changes is based on their expected direction of change. In an alternative embodiment, the amplitude score is based on quantity effects.

Having described our invention, what we now claim is as follows. 
     
         1 . A non-transitory computer-readable storage medium storing a computer readable program of computer instructions, the computer readable program being executable on machine, comprising:
 program code to receive a signature that is a collection of measured gene expression node entities and their expected directions of change with respect to a reference node in a biological network, the reference node representing a particular molecular activity in association with a particular protein, the collection of measured gene expression node entities being entities downstream of the reference node;   program code to assess a degree of activation of the signature by scoring one or more data sets against the signature; and   program code to infer activity of the particular protein from the degree of activation of the downstream measured gene expression node entities in lieu of direct biological measurements of the particular molecular activity.   
     
     
         2 . The computer-readable storage medium as described in  claim 1  wherein the degree of activation is a sum of adjusted log-fold changes of measured gene expression node entities in the signature divided by a number of gene expression node entities in the signature. 
     
     
         3 . The computer-readable storage medium as described in  claim 1  wherein the signature is derived from a knowledge base, wherein the knowledge base is a directed network of causal relationships among biological entities and processes.