Reverse Engineering Gene Networks with ANN: Variability in Network Inference Algorithms

Motivation :Reconstructing the topology of a gene regulatory network is one of the key tasks in systems biology. Despite of the wide variety of proposed methods, very little work has been dedicated to the assessment of their stability properties. Here we present a methodical comparison of the performance of a novel method (RegnANN) for gene network inference based on multilayer perceptrons with three reference algorithms (ARACNE, CLR, KELLER), focussing our analysis on the prediction variability induced by both the network intrinsic structure and the available data. Results: The extensive evaluation on both synthetic data and a selection of gene modules of "Escherichia coli" indicates that all the algorithms suffer of instability and variability issues with regards to the reconstruction of the topology of the network. This instability makes objectively very hard the task of establishing which method performs best. Nevertheless, RegnANN shows MCC scores that compare very favorably with all the other inference methods tested. Availability: The software for the RegnANN inference algorithm is distributed under GPL3 and it is available at the corresponding author home page (http://mpba.fbk.eu/grimaldi/regnann-supmat

Heterogeneous network flow and Petri nets characterize multilayer complex networks

Interacting subsystems are commonly described by networks, where multimodal behaviour found in most natural or engineered systems found recent extension in form of multilayer networks. Since multimodal interaction is often not dictated by network topology alone and may manifest in form of cross-layer information exchange, multilayer network flow becomes of relevant further interest. Rationale can be found in most interacting subsystems, where a form of multimodal flow across layers can be observed in e.g., chemical processes, energy networks, logistics, finance, or any other form of conversion process relying on the laws of conservation. To this end, the formal notion of heterogeneous network flow is proposed, as a multilayer flow function aligned with the theory of network flow. Furthermore, dynamic equivalence is established with the framework of Petri nets, as the baseline model of concurrent event systems. Application of the resulting multilayer Laplacian flow and flow centrality is presented, along with graph learning based inference of multilayer relationships over multimodal data. On synthetic data the proposed framework demonstrates benefits of multimodal flow derivation in critical component identification. It also displays applicability in relationship inference (learning based function approximation) on multimodal time series. On real-world data the proposed framework provides, among others, multimodal flow interpretation of U.S. economic activity, uncovering underlying empirical steady state probability distribution, as well as inherent network (economic) robustness

The Integration of Connectionism and First-Order Knowledge Representation and Reasoning as a Challenge for Artificial Intelligence

Intelligent systems based on first-order logic on the one hand, and on artificial neural networks (also called connectionist systems) on the other, differ substantially. It would be very desirable to combine the robust neural networking machinery with symbolic knowledge representation and reasoning paradigms like logic programming in such a way that the strengths of either paradigm will be retained. Current state-of-the-art research, however, fails by far to achieve this ultimate goal. As one of the main obstacles to be overcome we perceive the question how symbolic knowledge can be encoded by means of connectionist systems: Satisfactory answers to this will naturally lead the way to knowledge extraction algorithms and to integrated neural-symbolic systems.Comment: In Proceedings of INFORMATION'2004, Tokyo, Japan, to appear. 12 page

Bayesian nonparametric sparse VAR models

High dimensional vector autoregressive (VAR) models require a large number of parameters to be estimated and may suffer of inferential problems. We propose a new Bayesian nonparametric (BNP) Lasso prior (BNP-Lasso) for high-dimensional VAR models that can improve estimation efficiency and prediction accuracy. Our hierarchical prior overcomes overparametrization and overfitting issues by clustering the VAR coefficients into groups and by shrinking the coefficients of each group toward a common location. Clustering and shrinking effects induced by the BNP-Lasso prior are well suited for the extraction of causal networks from time series, since they account for some stylized facts in real-world networks, which are sparsity, communities structures and heterogeneity in the edges intensity. In order to fully capture the richness of the data and to achieve a better understanding of financial and macroeconomic risk, it is therefore crucial that the model used to extract network accounts for these stylized facts.Comment: Forthcoming in "Journal of Econometrics" ---- Revised Version of the paper "Bayesian nonparametric Seemingly Unrelated Regression Models" ---- Supplementary Material available on reques