An Abstraction Theory for Qualitative Models of Biological Systems

Multi-valued network models are an important qualitative modelling approach used widely by the biological community. In this paper we consider developing an abstraction theory for multi-valued network models that allows the state space of a model to be reduced while preserving key properties of the model. This is important as it aids the analysis and comparison of multi-valued networks and in particular, helps address the well-known problem of state space explosion associated with such analysis. We also consider developing techniques for efficiently identifying abstractions and so provide a basis for the automation of this task. We illustrate the theory and techniques developed by investigating the identification of abstractions for two published MVN models of the lysis-lysogeny switch in the bacteriophage lambda.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005

Basins of Attraction, Commitment Sets and Phenotypes of Boolean Networks

The attractors of Boolean networks and their basins have been shown to be highly relevant for model validation and predictive modelling, e.g., in systems biology. Yet there are currently very few tools available that are able to compute and visualise not only attractors but also their basins. In the realm of asynchronous, non-deterministic modeling not only is the repertoire of software even more limited, but also the formal notions for basins of attraction are often lacking. In this setting, the difficulty both for theory and computation arises from the fact that states may be ele- ments of several distinct basins. In this paper we address this topic by partitioning the state space into sets that are committed to the same attractors. These commitment sets can easily be generalised to sets that are equivalent w.r.t. the long-term behaviours of pre-selected nodes which leads us to the notions of markers and phenotypes which we illustrate in a case study on bladder tumorigenesis. For every concept we propose equivalent CTL model checking queries and an extension of the state of the art model checking software NuSMV is made available that is capa- ble of computing the respective sets. All notions are fully integrated as three new modules in our Python package PyBoolNet, including functions for visualising the basins, commitment sets and phenotypes as quotient graphs and pie charts

Abstracting Asynchronous Multi-Valued Networks: An Initial Investigation

Multi-valued networks provide a simple yet expressive qualitative state based modelling approach for biological systems. In this paper we develop an abstraction theory for asynchronous multi-valued network models that allows the state space of a model to be reduced while preserving key properties of the model. The abstraction theory therefore provides a mechanism for coping with the state space explosion problem and supports the analysis and comparison of multi-valued networks. We take as our starting point the abstraction theory for synchronous multi-valued networks which is based on the finite set of traces that represent the behaviour of such a model. The problem with extending this approach to the asynchronous case is that we can now have an infinite set of traces associated with a model making a simple trace inclusion test infeasible. To address this we develop a decision procedure for checking asynchronous abstractions based on using the finite state graph of an asynchronous multi-valued network to reason about its trace semantics. We illustrate the abstraction techniques developed by considering a detailed case study based on a multi-valued network model of the regulation of tryptophan biosynthesis in Escherichia coli.Comment: Presented at MeCBIC 201

Controllability Metrics on Networks with Linear Decision Process-type Interactions and Multiplicative Noise

This paper aims at the study of controllability properties and induced controllability metrics on complex networks governed by a class of (discrete time) linear decision processes with mul-tiplicative noise. The dynamics are given by a couple consisting of a Markov trend and a linear decision process for which both the "deterministic" and the noise components rely on trend-dependent matrices. We discuss approximate, approximate null and exact null-controllability. Several examples are given to illustrate the links between these concepts and to compare our results with their continuous-time counterpart (given in [16]). We introduce a class of backward stochastic Riccati difference schemes (BSRDS) and study their solvability for particular frameworks. These BSRDS allow one to introduce Gramian-like controllability metrics. As application of these metrics, we propose a minimal intervention-targeted reduction in the study of gene networks

CHR(PRISM)-based Probabilistic Logic Learning

PRISM is an extension of Prolog with probabilistic predicates and built-in support for expectation-maximization learning. Constraint Handling Rules (CHR) is a high-level programming language based on multi-headed multiset rewrite rules. In this paper, we introduce a new probabilistic logic formalism, called CHRiSM, based on a combination of CHR and PRISM. It can be used for high-level rapid prototyping of complex statistical models by means of "chance rules". The underlying PRISM system can then be used for several probabilistic inference tasks, including probability computation and parameter learning. We define the CHRiSM language in terms of syntax and operational semantics, and illustrate it with examples. We define the notion of ambiguous programs and define a distribution semantics for unambiguous programs. Next, we describe an implementation of CHRiSM, based on CHR(PRISM). We discuss the relation between CHRiSM and other probabilistic logic programming languages, in particular PCHR. Finally we identify potential application domains

Neural Nearest Neighbors Networks

Non-local methods exploiting the self-similarity of natural signals have been well studied, for example in image analysis and restoration. Existing approaches, however, rely on k-nearest neighbors (KNN) matching in a fixed feature space. The main hurdle in optimizing this feature space w.r.t. application performance is the non-differentiability of the KNN selection rule. To overcome this, we propose a continuous deterministic relaxation of KNN selection that maintains differentiability w.r.t. pairwise distances, but retains the original KNN as the limit of a temperature parameter approaching zero. To exploit our relaxation, we propose the neural nearest neighbors block (N3 block), a novel non-local processing layer that leverages the principle of self-similarity and can be used as building block in modern neural network architectures. We show its effectiveness for the set reasoning task of correspondence classification as well as for image restoration, including image denoising and single image super-resolution, where we outperform strong convolutional neural network (CNN) baselines and recent non-local models that rely on KNN selection in hand-chosen features spaces.Comment: to appear at NIPS*2018, code available at https://github.com/visinf/n3net