Assessment of network inference methods: how to cope with an underdetermined problem

PLoS One. 2014 Mar 6;9(3):e90481. doi: 10.1371/journal.pone.0090481. eCollection 2014.

Abstract

The inference of biological networks is an active research area in the field of systems biology. The number of network inference algorithms has grown tremendously in the last decade, underlining the importance of a fair assessment and comparison among these methods. Current assessments of the performance of an inference method typically involve the application of the algorithm to benchmark datasets and the comparison of the network predictions against the gold standard or reference networks. While the network inference problem is often deemed underdetermined, implying that the inference problem does not have a (unique) solution, the consequences of such an attribute have not been rigorously taken into consideration. Here, we propose a new procedure for assessing the performance of gene regulatory network (GRN) inference methods. The procedure takes into account the underdetermined nature of the inference problem, in which gene regulatory interactions that are inferable or non-inferable are determined based on causal inference. The assessment relies on a new definition of the confusion matrix, which excludes errors associated with non-inferable gene regulations. For demonstration purposes, the proposed assessment procedure is applied to the DREAM 4 In Silico Network Challenge. The results show a marked change in the ranking of participating methods when taking network inferability into account.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Graphics
  • Gene Knockdown Techniques
  • Gene Knockout Techniques
  • Gene Regulatory Networks*
  • Systems Biology / methods*

Grants and funding

The study was supported by the Swiss National Science Foundation (project number 200021-137614). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.