Boolean Delay Equations: A simple way of looking at complex systems

Boolean Delay Equations (BDEs) are semi-discrete dynamical models with Boolean-valued variables that evolve in continuous time. Systems of BDEs can be classified into conservative or dissipative, in a manner that parallels the classification of ordinary or partial differential equations. Solutions to certain conservative BDEs exhibit growth of complexity in time. They represent therewith metaphors for biological evolution or human history. Dissipative BDEs are structurally stable and exhibit multiple equilibria and limit cycles, as well as more complex, fractal solution sets, such as Devil's staircases and ``fractal sunbursts``. All known solutions of dissipative BDEs have stationary variance. BDE systems of this type, both free and forced, have been used as highly idealized models of climate change on interannual, interdecadal and paleoclimatic time scales. BDEs are also being used as flexible, highly efficient models of colliding cascades in earthquake modeling and prediction, as well as in genetics. In this paper we review the theory of systems of BDEs and illustrate their applications to climatic and solid earth problems. The former have used small systems of BDEs, while the latter have used large networks of BDEs. We moreover introduce BDEs with an infinite number of variables distributed in space (``partial BDEs``) and discuss connections with other types of dynamical systems, including cellular automata and Boolean networks. This research-and-review paper concludes with a set of open questions.Comment: Latex, 67 pages with 15 eps figures. Revised version, in particular the discussion on partial BDEs is updated and enlarge

Control of stochastic and induced switching in biophysical networks

Noise caused by fluctuations at the molecular level is a fundamental part of intracellular processes. While the response of biological systems to noise has been studied extensively, there has been limited understanding of how to exploit it to induce a desired cell state. Here we present a scalable, quantitative method based on the Freidlin-Wentzell action to predict and control noise-induced switching between different states in genetic networks that, conveniently, can also control transitions between stable states in the absence of noise. We apply this methodology to models of cell differentiation and show how predicted manipulations of tunable factors can induce lineage changes, and further utilize it to identify new candidate strategies for cancer therapy in a cell death pathway model. This framework offers a systems approach to identifying the key factors for rationally manipulating biophysical dynamics, and should also find use in controlling other classes of noisy complex networks.Comment: A ready-to-use code package implementing the method described here is available from the authors upon reques

Intervention in Context-Sensitive Probabilistic Boolean Networks Revisited

An approximate representation for the state space of a context-sensitive probabilistic Boolean network has previously been proposed and utilized to devise therapeutic intervention strategies. Whereas the full state of a context-sensitive probabilistic Boolean network is specified by an ordered pair composed of a network context and a gene-activity profile, this approximate representation collapses the state space onto the gene-activity profiles alone. This reduction yields an approximate transition probability matrix, absent of context, for the Markov chain associated with the context-sensitive probabilistic Boolean network. As with many approximation methods, a price must be paid for using a reduced model representation, namely, some loss of optimality relative to using the full state space. This paper examines the effects on intervention performance caused by the reduction with respect to various values of the model parameters. This task is performed using a new derivation for the transition probability matrix of the context-sensitive probabilistic Boolean network. This expression of transition probability distributions is in concert with the original definition of context-sensitive probabilistic Boolean network. The performance of optimal and approximate therapeutic strategies is compared for both synthetic networks and a real case study. It is observed that the approximate representation describes the dynamics of the context-sensitive probabilistic Boolean network through the instantaneously random probabilistic Boolean network with similar parameters

Scalable Facility Location for Massive Graphs on Pregel-like Systems

We propose a new scalable algorithm for facility location. Facility location is a classic problem, where the goal is to select a subset of facilities to open, from a set of candidate facilities F , in order to serve a set of clients C. The objective is to minimize the total cost of opening facilities plus the cost of serving each client from the facility it is assigned to. In this work, we are interested in the graph setting, where the cost of serving a client from a facility is represented by the shortest-path distance on the graph. This setting allows to model natural problems arising in the Web and in social media applications. It also allows to leverage the inherent sparsity of such graphs, as the input is much smaller than the full pairwise distances between all vertices. To obtain truly scalable performance, we design a parallel algorithm that operates on clusters of shared-nothing machines. In particular, we target modern Pregel-like architectures, and we implement our algorithm on Apache Giraph. Our solution makes use of a recent result to build sketches for massive graphs, and of a fast parallel algorithm to find maximal independent sets, as building blocks. In so doing, we show how these problems can be solved on a Pregel-like architecture, and we investigate the properties of these algorithms. Extensive experimental results show that our algorithm scales gracefully to graphs with billions of edges, while obtaining values of the objective function that are competitive with a state-of-the-art sequential algorithm