A Computational Algebra Approach to the Reverse Engineering of Gene Regulatory Networks

This paper proposes a new method to reverse engineer gene regulatory networks from experimental data. The modeling framework used is time-discrete deterministic dynamical systems, with a finite set of states for each of the variables. The simplest examples of such models are Boolean networks, in which variables have only two possible states. The use of a larger number of possible states allows a finer discretization of experimental data and more than one possible mode of action for the variables, depending on threshold values. Furthermore, with a suitable choice of state set, one can employ powerful tools from computational algebra, that underlie the reverse-engineering algorithm, avoiding costly enumeration strategies. To perform well, the algorithm requires wildtype together with perturbation time courses. This makes it suitable for small to meso-scale networks rather than networks on a genome-wide scale. The complexity of the algorithm is quadratic in the number of variables and cubic in the number of time points. The algorithm is validated on a recently published Boolean network model of segment polarity development in Drosophila melanogaster.Comment: 28 pages, 5 EPS figures, uses elsart.cl

A Mathematical Framework for Agent Based Models of Complex Biological Networks

Agent-based modeling and simulation is a useful method to study biological phenomena in a wide range of fields, from molecular biology to ecology. Since there is currently no agreed-upon standard way to specify such models it is not always easy to use published models. Also, since model descriptions are not usually given in mathematical terms, it is difficult to bring mathematical analysis tools to bear, so that models are typically studied through simulation. In order to address this issue, Grimm et al. proposed a protocol for model specification, the so-called ODD protocol, which provides a standard way to describe models. This paper proposes an addition to the ODD protocol which allows the description of an agent-based model as a dynamical system, which provides access to computational and theoretical tools for its analysis. The mathematical framework is that of algebraic models, that is, time-discrete dynamical systems with algebraic structure. It is shown by way of several examples how this mathematical specification can help with model analysis.Comment: To appear in Bulletin of Mathematical Biolog

Reverse-engineering of polynomial dynamical systems

Multivariate polynomial dynamical systems over finite fields have been studied in several contexts, including engineering and mathematical biology. An important problem is to construct models of such systems from a partial specification of dynamic properties, e.g., from a collection of state transition measurements. Here, we consider static models, which are directed graphs that represent the causal relationships between system variables, so-called wiring diagrams. This paper contains an algorithm which computes all possible minimal wiring diagrams for a given set of state transition measurements. The paper also contains several statistical measures for model selection. The algorithm uses primary decomposition of monomial ideals as the principal tool. An application to the reverse-engineering of a gene regulatory network is included. The algorithm and the statistical measures are implemented in Macaulay2 and are available from the authors

Formal Analysis of Arithmetic Circuits using Computer Algebra - Verification, Abstraction and Reverse Engineering

Despite a considerable progress in verification and abstraction of random and control logic, advances in formal verification of arithmetic designs have been lagging. This can be attributed mostly to the difficulty in an efficient modeling of arithmetic circuits and datapaths without resorting to computationally expensive Boolean methods, such as Binary Decision Diagrams (BDDs) and Boolean Satisfiability (SAT), that require “bit blasting”, i.e., flattening the design to a bit-level netlist. Approaches that rely on computer algebra and Satisfiability Modulo Theories (SMT) methods are either too abstract to handle the bit-level nature of arithmetic designs or require solving computationally expensive decision or satisfiability problems. The work proposed in this thesis aims at overcoming the limitations of analyzing arithmetic circuits, specifically at the post-synthesized phase. It addresses the verification, abstraction and reverse engineering problems of arithmetic circuits at an algebraic level, treating an arithmetic circuit and its specification as a properly constructed algebraic system. The proposed technique solves these problems by function extraction, i.e., by deriving arithmetic function computed by the circuit from its low-level circuit implementation using computer algebraic rewriting technique. The proposed techniques work on large integer arithmetic circuits and finite field arithmetic circuits, up to 512-bit wide containing millions of logic gates

Synthesis and Optimization of Reversible Circuits - A Survey

Reversible logic circuits have been historically motivated by theoretical research in low-power electronics as well as practical improvement of bit-manipulation transforms in cryptography and computer graphics. Recently, reversible circuits have attracted interest as components of quantum algorithms, as well as in photonic and nano-computing technologies where some switching devices offer no signal gain. Research in generating reversible logic distinguishes between circuit synthesis, post-synthesis optimization, and technology mapping. In this survey, we review algorithmic paradigms --- search-based, cycle-based, transformation-based, and BDD-based --- as well as specific algorithms for reversible synthesis, both exact and heuristic. We conclude the survey by outlining key open challenges in synthesis of reversible and quantum logic, as well as most common misconceptions.Comment: 34 pages, 15 figures, 2 table

Counterexample-Guided Polynomial Loop Invariant Generation by Lagrange Interpolation

We apply multivariate Lagrange interpolation to synthesize polynomial quantitative loop invariants for probabilistic programs. We reduce the computation of an quantitative loop invariant to solving constraints over program variables and unknown coefficients. Lagrange interpolation allows us to find constraints with less unknown coefficients. Counterexample-guided refinement furthermore generates linear constraints that pinpoint the desired quantitative invariants. We evaluate our technique by several case studies with polynomial quantitative loop invariants in the experiments