Louis Wehenkel

One of the pressing open problems of computational systems biology is the elucidation of the topology of genetic regulatory networks (GRNs) using high throughput genomic data, in particular microarray gene expression data. The Dialogue for Reverse Engineering Assessments and Methods (DREAM) challenge aims to evaluate the success of GRN inference algorithms on benchmarks of simulated data. In this article, we present GENIE3, a new algorithm for the inference of GRNs that was best performer in the DREAM4 In Silico Multifactorial challenge. GENIE3 decomposes the prediction of a regulatory network between p genes into p different regression problems. In each of the regression problems, the expression pattern of one of the genes (target gene) is predicted from the expression patterns of all the other genes (input genes), using tree-based ensemble methods Random Forests or Extra-Trees. The importance of an input gene in the prediction of the target gene expression pattern is taken as an indication of a putative regulatory link. Putative regulatory links are then aggregated over all genes to provide a ranking of interactions from which the whole network is reconstructed. In addition to performing well on the DREAM4 In Silico Multifactorial challenge simulated data, we show that GENIE3 compares favorably with existing algorithms to decipher the genetic regulatory network of Escherichia coli. It doesn't make any assumption about the nature of gene regulation, can deal with combinatorial and non-linear interactions, produces directed GRNs, and is fast and scalable. In conclusion, we propose a new algorithm for GRN inference that performs well on both synthetic and real gene expression data. The algorithm, based on feature selection with tree-based ensemble methods, is simple and generic, making it adaptable to other types of genomic data and interactions.

Reinforcement learning aims to determine an optimal control policy from interaction with a system or from observations gathered from a system. In batch mode, it can be achieved by approximating the so-called Q-function based on a set of four-tuples (xt,ut,rt,xt+1) where xt denotes the system state at time t, ut the control action taken, rt the instantaneous reward obtained and xt+1 the successor state of the system, and by determining the control policy from this Q-function. The Q-function approximation may be obtained from the limit of a sequence of (batch mode) supervised learning problems. Within this framework we describe the use of several classical tree-based supervised learning methods (CART, Kd-tree, tree bagging) and two newly proposed ensemble algorithms, namely extremely and totally randomized trees. We study their performances on several examples and find that the ensemble methods based on regression trees perform well in extracting relevant information about the optimal control policy from sets of four-tuples. In particular, the totally randomized trees give good results while ensuring the convergence of the sequence, whereas by relaxing the convergence constraint even better accuracy results are provided by the extremely randomized trees.

peer reviewed