Study of Normalization and Aggregation Approaches for Consensus Network Estimation

Inferring gene regulatory networks from expression data is a very difficult problem that has raised the interest of the scientific community. Different algorithms have been proposed to try to solve this issue, but it has been shown that the different methods have some particular biases and strengths, and none of them is the best across all types of data and datasets. As a result, the idea of aggregating various network inferences through a consensus mechanism naturally arises. In this paper, a common framework to standardize already proposed consensus methods is presented, and based on this framework different proposals are introduced and analyzed in two different scenarios: Homogeneous and Heterogeneous. The first scenario reflects situations where the networks to be aggregated are rather similar because the are obtained with inference algorithms working on the same data, whereas the second scenario deals with very diverse networks because various sources of data are used to generate the individual networks. A procedure for combining multiple network inference algorithms is analyzed in a systematic way. The results show that there is a very significant difference between these two scenarios, and that the best way to combine networks in the Heterogeneous scenario is not the most commonly used. We show in particular that aggregation in the Heterogeneous scenario can be very beneficial if the individual networks are combined with our new proposed method Scale LSum.