Symbolic regression of generative network models

Networks are a powerful abstraction with applicability to a variety of scientific fields. Models explaining their morphology and growth processes permit a wide range of phenomena to be more systematically analysed and understood. At the same time, creating such models is often challenging and requires insights that may be counter-intuitive. Yet there currently exists no general method to arrive at better models. We have developed an approach to automatically detect realistic decentralised network growth models from empirical data, employing a machine learning technique inspired by natural selection and defining a unified formalism to describe such models as computer programs. As the proposed method is completely general and does not assume any pre-existing models, it can be applied "out of the box" to any given network. To validate our approach empirically, we systematically rediscover pre-defined growth laws underlying several canonical network generation models and credible laws for diverse real-world networks. We were able to find programs that are simple enough to lead to an actual understanding of the mechanisms proposed, namely for a simple brain and a social network

Object-Oriented Genetic Programming for the Automatic Inference of Graph Models for Complex Networks

Complex networks are systems of entities that are interconnected through meaningful relationships. The result of the relations between entities forms a structure that has a statistical complexity that is not formed by random chance. In the study of complex networks, many graph models have been proposed to model the behaviours observed. However, constructing graph models manually is tedious and problematic. Many of the models proposed in the literature have been cited as having inaccuracies with respect to the complex networks they represent. However, recently, an approach that automates the inference of graph models was proposed by Bailey [10] The proposed methodology employs genetic programming (GP) to produce graph models that approximate various properties of an exemplary graph of a targeted complex network. However, there is a great deal already known about complex networks, in general, and often specific knowledge is held about the network being modelled. The knowledge, albeit incomplete, is important in constructing a graph model. However it is difficult to incorporate such knowledge using existing GP techniques. Thus, this thesis proposes a novel GP system which can incorporate incomplete expert knowledge that assists in the evolution of a graph model. Inspired by existing graph models, an abstract graph model was developed to serve as an embryo for inferring graph models of some complex networks. The GP system and abstract model were used to reproduce well-known graph models. The results indicated that the system was able to evolve models that produced networks that had structural similarities to the networks generated by the respective target models

Revisiting the Training of Logic Models of Protein Signaling Networks with a Formal Approach based on Answer Set Programming

A fundamental question in systems biology is the construction and training to data of mathematical models. Logic formalisms have become very popular to model signaling networks because their simplicity allows us to model large systems encompassing hundreds of proteins. An approach to train (Boolean) logic models to high-throughput phospho-proteomics data was recently introduced and solved using optimization heuristics based on stochastic methods. Here we demonstrate how this problem can be solved using Answer Set Programming (ASP), a declarative problem solving paradigm, in which a problem is encoded as a logical program such that its answer sets represent solutions to the problem. ASP has significant improvements over heuristic methods in terms of efficiency and scalability, it guarantees global optimality of solutions as well as provides a complete set of solutions. We illustrate the application of ASP with in silico cases based on realistic networks and data

Network estimation in State Space Model with L1-regularization constraint

Biological networks have arisen as an attractive paradigm of genomic science ever since the introduction of large scale genomic technologies which carried the promise of elucidating the relationship in functional genomics. Microarray technologies coupled with appropriate mathematical or statistical models have made it possible to identify dynamic regulatory networks or to measure time course of the expression level of many genes simultaneously. However one of the few limitations fall on the high-dimensional nature of such data coupled with the fact that these gene expression data are known to include some hidden process. In that regards, we are concerned with deriving a method for inferring a sparse dynamic network in a high dimensional data setting. We assume that the observations are noisy measurements of gene expression in the form of mRNAs, whose dynamics can be described by some unknown or hidden process. We build an input-dependent linear state space model from these hidden states and demonstrate how an incorporated $L_{1}$ regularization constraint in an Expectation-Maximization (EM) algorithm can be used to reverse engineer transcriptional networks from gene expression profiling data. This corresponds to estimating the model interaction parameters. The proposed method is illustrated on time-course microarray data obtained from a well established T-cell data. At the optimum tuning parameters we found genes TRAF5, JUND, CDK4, CASP4, CD69, and C3X1 to have higher number of inwards directed connections and FYB, CCNA2, AKT1 and CASP8 to be genes with higher number of outwards directed connections. We recommend these genes to be object for further investigation. Caspase 4 is also found to activate the expression of JunD which in turn represses the cell cycle regulator CDC2.Comment: arXiv admin note: substantial text overlap with arXiv:1308.359