Exploiting causality in gene network reconstruction based on graph embedding

摘要

Gene network reconstruction is a bioinformatics task that aims at modelling the complex regulatory activities that may occur among genes. This task is typically solved by means of link prediction methods that analyze gene expression data. However, the reconstructed networks often suffer from a high amount of false positive edges, which are actually the result of indirect regulation activities due to the presence of common cause and common effect phenomena or, in other terms, due to the fact that the adopted inductive methods do not take into account possible causality phenomena. This issue is accentuated even more by the inherent presence of a high amount of noise in gene expression data. Existing methods for the identification of a transitive reduction of a network or for the removal of (possibly) redundant edges suffer from limitations in the structure of the network or in the nature/length of the indirect regulation, and often require additional pre-processing steps to handle specific peculiarities of the networks (e.g., cycles). Moreover, they are not able to consider possible community structures and possible similar roles of the genes in the network (e.g. hub nodes), which may change the tendency of nodes to be highly connected (and with which nodes) in the network. In this paper, we propose the method INLOCANDA, which learns an inductive predictive model for gene network reconstruction and overcomes all the mentioned limitations. In particular, INLOCANDA is able to (i) identify and exploit indirect relationships of arbitrary length to remove edges due to common cause and common effect phenomena; (ii) take into account possible community structures and possible similar roles by means of graph embedding. Experiments performed along multiple dimensions of analysis on benchmark, real networks of two organisms (E. coli and S. cerevisiae) show a higher accuracy with respect to the competitors, as well as a higher robustness to the presence of noise in the data, also when a huge amount of (possibly false positive) interactions is removed. Availability: http://www.di.uniba.it/~gianvitopio/systems/inlocanda/