Inferring Transcription Networks from Data

Abstract

Reverse engineering of transcription networks is a challenging bioinformatics problem. Ordinary differential equation (ODEs) network models have their roots in the physicochemical base of these networks, but are difficult to build conventionally. Modeling automation is needed and knowledge discovery in data using computational intelligence methods is a solution. The authors have developed a methodology for automatically inferring ODE systems models from omics data, based on genetic programming (GP), and illustrate it on a real transcription network. The methodology allows the network to be decomposed from the complex of interacting cellular networks and to further decompose each of its nodes, without destroying their interactions. The structure of the network is not imposed but discovered from data, and further assumptions can be made about the parametersʼ values and the mechanisms involved. The algorithms can deal with unmeasured regulatory variables, like transcription factors (TFs) and microRNA (miRNA or miR). This is possible by introducing the regulome probabilities concept and the techniques to compute them. They are based on the statistical thermodynamics of regulatory molecular interactions. Thus, the resultant models are mechanistic and theoretically founded, not merely data fittings. To our knowledge, this is the first reverse engineering approach capable of dealing with missing variables, and the accuracy of all the models developed is greater than 99%.