| Publications about 'algorithms' |
| Articles in journal or book chapters |
| We introduce the notion of non-oscillation, propose a constructive method for its robust verification, and study its application to biological interaction networks (also known as, chemical reaction networks). We begin by revisiting Muldowney's result on non-existence of periodic solutions based on the study of the variational system of the second additive compound of the Jacobian of a nonlinear system. We show that exponential stability of the latter rules out limit cycles, quasi-periodic solutions, and broad classes of oscillatory behavior. We focus then on nonlinear equations arising in biological interaction networks with general kinetics, and we show that the dynamics of the aforementioned variational system can be embedded in a linear differential inclusion. We then propose algorithms for constructing piecewise linear Lyapunov functions to certify global robust non-oscillatory behavior. Finally, we apply our techniques to study several regulated enzymatic cycles where available methods are not able to provide any information about their qualitative global behavior. |
| This work introduces an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network. |
| We present a novel computational method, and related software, to synthesize signal transduction networks from single and double causal evidence. |
| Multivariate Poisson random variables subject to linear integer constraints arise in several application areas, such as queuing and biomolecular networks. This note shows how to compute conditional statistics in this context, by employing WZ Theory and associated algorithms. A symbolic computation package has been developed and is made freely available. A discussion of motivating biomolecular problems is also provided. |
| The transitive reduction problem is that of inferring a sparsest possible biological signal transduction network consistent with a set of experimental observations, with a goal to minimize false positive inferences even if risking false negatives. This paper provides computational complexity results as well as approximation algorithms with guaranteed performance. |
| This paper presents a software tool for inference and simplification of signal transduction networks. The method relies on the representation of observed indirect causal relationships as network paths, using techniques from combinatorial optimization to find the sparsest graph consistent with all experimental observations. We illustrate the biological usability of our software by applying it to a previously published signal transduction network and by using it to synthesize and simplify a novel network corresponding to activation-induced cell death in large granular lymphocyte leukemia. |
| This paper introduces a new method of combined synthesis and inference of biological signal transduction networks. The main idea lies in representing observed causal relationships as network paths, and using techniques from combinatorial optimization to find the sparsest graph consistent with all experimental observations. The paper formalizes the approach, studies its computational complexity, proves new results for exact and approximate solutions of the computationally hard transitive reduction substep of the approach, validates the biological applicability by applying it to a previously published signal transduction network by Li et al., and shows that the algorithm for the transitive reduction substep performs well on graphs with a structure similar to those observed in transcriptional regulatory and signal transduction networks. |
| This paper studies a computational problem motivated by the modular response analysis method for reverse engineering of protein and gene networks. This set-cover problem is hard to solve exactly for large networks, but efficient approximation algorithms are given and their complexity is analyzed. |
| This paper investigates computational complexity aspects of a combinatorial problem that arises in the reverse engineering of protein and gene networks, showing relations to an appropriate set multicover problem with large "coverage" factor, and providing a non-trivial analysis of a simple randomized polynomial-time approximation algorithm for the problem. |
| A useful approach to the mathematical analysis of large-scale biological networks is based upon their decompositions into monotone dynamical systems. This paper deals with two computational problems associated to finding decompositions which are optimal in an appropriate sense. In graph-theoretic language, the problems can be recast in terms of maximal sign-consistent subgraphs. The theoretical results include polynomial-time approximation algorithms as well as constant-ratio inapproximability results. One of the algorithms, which has a worst-case guarantee of 87.9% from optimality, is based on the semidefinite programming relaxation approach of Goemans-Williamson. The algorithm was implemented and tested on a Drosophila segmentation network and an Epidermal Growth Factor Receptor pathway model. |
| This paper investigates the problem of searching for a hidden target in a bounded region of the plane by an autonomous robot which is only able to use limited local sensory information. It proposes an aggregation-based approach to solve this problem, in which the continuous search space is partitioned into a finite collection of regions on which we define a discrete search problem and a solution to the original problem is obtained through a refinement procedure that lifts the discrete path into a continuous one. The resulting solution is in general not optimal but one can construct bounds to gauge the cost penalty incurred. The discrete version is formalized and an optimization problem is stated as a `reward-collecting' bounded-length path problem. NP-completeness and efficient approximation algorithms for various cases of this problem are discussed. |
| A state-space realization theory is presented for a wide class of discrete time input/output behaviors. Although In many ways restricted, this class does include as particular cases those treated in the literature (linear, multilinear, internally bilinear, homogeneous), as well ss certain nonanalytic nonlinearities. The theory is conceptually simple, and matrix-theoretic algorithms are straightforward. Finite-realizability of these behaviors by state-affine systems is shown to be equivalent both to the existence of high-order input/output equadons and to realizability by more general types of systems. |
| Conference articles |
| In this paper we investigate the problem of searching for a hidden target in a bounded region of the plane, by an autonomous robot which is only able to use limited local sensory information. We formalize a discrete version of the problem as a "reward-collecting" path problem and provide efficient approximation algorithms for various cases. |
| Internal reports |
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