Genetic Network Inference Using Hierarchical Structure

Abstract

Many methods for inferring genetic networks have been proposed, but the regulations they infer often include false-positives. Several researchers have attempted to reduce these erroneous regulations by proposing the use of a priori knowledge about the properties of genetic networks such as their sparseness, scale-free structure, and so on. This study focuses on another piece of a priori knowledge, namely, that biochemical networks exhibit hierarchical structures. Based on this idea, we propose an inference approach that uses the hierarchical structure in a target genetic network. To obtain a reasonable hierarchical structure, the first step of the proposed approach is to infer multiple genetic networks from the observed gene expression data. We take this step using an existing method that combines a genetic network inference method with a bootstrap method. The next step is to extract a hierarchical structure from the inferred networks that is consistent with most of the networks. Third, we use the hierarchical structure obtained to assign confidence values to all candidate regulations. Numerical experiments are also performed to demonstrate the effectiveness of using the hierarchical structure in the genetic network inference. The improvement accomplished by the use of the hierarchical structure is small. However, the hierarchical structure could be used to improve the performances of many existing inference methods.

Using A Priori Knowledge after Genetic Network Inference: Integrating Multiple Kinds of Knowledge

“…0 ( ) is the AURPC of the inference method based on the hierarchical structure [8]. Note that, when the hierarchical structure is the only a priori knowledge used and the constant parameters , 0 and 1, respectively, the proposed method is equivalent to the inference method based on the hierarchical structure.…”

“…This study represents the confidence values evaluated based on the hierarchical structure as , (1) 's. In reference [8], readers can find a detailed algorithm to extract a hierarchical structure from multiple genetic networks.…”

“…The section 4 will describe a method to find the optimal values for these constants. Note that reference [8] simply combines the confidence values. Here, on the other hand, we combine them using the non-linear function g.…”

“…Our group recently proposed an inference method that uses another kind of a priori knowledge, i.e., a hierarchical structure [8]. The first step in this hierarchy-based method [8] is to obtain multiple genetic networks from the given gene expression data using the BS-LPM inference method [9], a combination of the existing inference method [10] and a bootstrap method [11].…”

“…The first step in this hierarchy-based method [8] is to obtain multiple genetic networks from the given gene expression data using the BS-LPM inference method [9], a combination of the existing inference method [10] and a bootstrap method [11]. The second step is to detect a hierarchical structure that is consistent with most of the inferred networks.…”