Genetic, Metabolic and Biochemical Pathway Analysis System and Methods

摘要

Identifying pathways that are significantly impacted in a given condition is a crucial step in the understanding of the underlying biological phenomena. All approaches currently available for this purpose calculate a p-value that aims to quantify the significance of the involvement of each pathway in the given phenotype. These p-values were previously thought to be independent. Here, we show that this is not the case, and that pathways can affect each other's p-values through a “crosstalk” phenomenon that affects all major categories of existing methods. We describe a novel technique able to detect, quantify, and correct crosstalk effects, as well as identify novel independent functional modules. We assessed this technique on data from four real experiments coming from three phenotypes involving two species.

主权项

1. A computer-implemented apparatus for studying biomolecular networks made up of biomolecular nodes that are linked as a plurality of nodes that define a pathway associated with a designated physical condition mediated by that pathway, comprising:
a memory circuit configured to define the following data structures: a node data structure storing data representing a node as having an associated measured difference attribute capable of being selectively set to one of a first state and a second state; a pathway data structure storing data representing plural pathways each pathway comprising a plurality of linked nodes as represented by said node data structure; a p-value data structure storing data in association with the pathway data structure representing probability values (p-values) indicating the probability that a pathway relates to a designated physical condition mediated by that pathway; at least one processor coupled to read and write data in and out of said memory circuit, where the at least one processor is programmed to execute the following operations: populate the pathway data structure and node data structure with data corresponding to at least a first pathway and a second pathway; manipulate the data stored in the pathway and node data structures to compute a p-value and store the computed p-values as first p-value data in the p-value data structure; manipulate the data stored in the pathway and node data structures to identify and remove from the pathway data structure intersecting nodes that are common to both first and second pathways to thereby define a modified data set; manipulate the modified data set to compute a p-value and store the computed p-values as second p-value data in the p-value data structure; compare the stored first and second p-value data and based on the comparison makes a determination whether crosstalk is present between the first and second pathways according to whether the first and second p-values differ from one another; and provide an indication to a user of the apparatus of whether crosstalk is present between the first and second pathways.