A linear programming approach for estimating the structure of a sparse linear genetic network from transcript profiling data

Background: A genetic network can be represented as a directed graph in which a node corresponds to a gene and a directed edge specifies the direction of influence of one gene on another. The reconstruction of such networks from transcript profiling data remains an important yet challenging endeavor. A transcript profile specifies the abundances of many genes in a biological sample of interest. Prevailing strategies for learning the structure of a genetic network from high-dimensional transcript profiling data assume sparsity and linearity. Many methods consider relatively small directed graphs, inferring graphs with up to a few hundred nodes. This work examines large undirected graphs representations of genetic networks, graphs with many thousands of nodes where an undirected edge between two nodes does not indicate the direction of influence, and the problem of estimating the structure of such a sparse linear genetic network (SLGN) from transcript profiling data. Results: The structure learning task is cast as a sparse linear regression problem which is then posed as a LASSO (l1-constrained fitting) problem and solved finally by formulating a Linear Program (LP). A bound on the Generalization Error of this approach is given in terms of the Leave-One-Out Error. The accuracy and utility of LP-SLGNs is assessed quantitatively and qualitatively using simulated and real data. The Dialogue for Reverse Engineering Assessments and Methods (DREAM) initiative provides gold standard data sets and evaluation metrics that enable and facilitate the comparison of algorithms for deducing the structure of networks. The structures of LP-SLGNs estimated from the INSILICO1, INSILICO2 and INSILICO3 simulated DREAM2 data sets are comparable to those proposed by the first and/or second ranked teams in the DREAM2 competition. The structures of LP-SLGNs estimated from two published Saccharomyces cerevisae cell cycle transcript profiling data sets capture known regulatory associations. In each S. cerevisiae LP-SLGN, the number of nodes with a particular degree follows an approximate power law suggesting that its degree distributions is similar to that observed in real-world networks. Inspection of these LP-SLGNs suggests biological hypotheses amenable to experimental verification. Conclusion: A statistically robust and computationally efficient LP-based method for estimating the topology of a large sparse undirected graph from high-dimensional data yields representations of genetic networks that are biologically plausible and useful abstractions of the structures of real genetic networks. Analysis of the statistical and topological properties of learned LP-SLGNs may have practical value; for example, genes with high random walk betweenness, a measure of the centrality of a node in a graph, are good candidates for intervention studies and hence integrated computational – experimental investigations designed to infer more realistic and sophisticated probabilistic directed graphical model representations of genetic networks. The LP-based solutions of the sparse linear regression problem described here may provide a method for learning the structure of transcription factor networks from transcript profiling and transcription factor binding motif data.

A new constraint programming approach for optimising a coal rail system

Because of the bottlenecking operations in a complex coal rail system, millions of dollars are costed by mining companies. To handle this issue, this paper investigates a real-world coal rail system and aims to optimise the coal railing operations under constraints of limited resources (e.g., limited number of locomotives and wagons). In the literature, most studies considered the train scheduling problem on a single-track railway network to be strongly NP-hard and thus developed metaheuristics as the main solution methods. In this paper, a new mathematical programming model is formulated and coded by optimization programming language based on a constraint programming (CP) approach. A new depth-first-search technique is developed and embedded inside the CP model to obtain the optimised coal railing timetable efficiently. Computational experiments demonstrate that high-quality solutions are obtainable in industry-scale applications. To provide insightful decisions, sensitivity analysis is conducted in terms of different scenarios and specific criteria. Keywords Train scheduling · Rail transportation · Coal mining · Constraint programming

A mathematical programming approach to optimal Markovian switching of Poisson arrival streams to queueing systems

Motivated by certain situations in manufacturing systems and communication networks, we look into the problem of maximizing the profit in a queueing system with linear reward and cost structure and having a choice of selecting the streams of Poisson arrivals according to an independent Markov chain. We view the system as a MMPP/GI/1 queue and seek to maximize the profits by optimally choosing the stationary probabilities of the modulating Markov chain. We consider two formulations of the optimization problem. The first one (which we call the PUT problem) seeks to maximize the profit per unit time whereas the second one considers the maximization of the profit per accepted customer (the PAC problem). In each of these formulations, we explore three separate problems. In the first one, the constraints come from bounding the utilization of an infinite capacity server; in the second one the constraints arise from bounding the mean queue length of the same queue; and in the third one the finite capacity of the buffer reflect as a set of constraints. In the problems bounding the utilization factor of the queue, the solutions are given by essentially linear programs, while the problems with mean queue length constraints are linear programs if the service is exponentially distributed. The problems modeling the finite capacity queue are non-convex programs for which global maxima can be found. There is a rich relationship between the solutions of the PUT and PAC problems. In particular, the PUT solutions always make the server work at a utilization factor that is no less than that of the PAC solutions.

Missile battery placement for air defense: A dynamic programming approach

A procedure to evaluate surface-to-air missile battery placement patterns for air defense is presented. A measure of defense effectiveness is defined as a function of kill probability of the defense missiles and the nature of the surrounding terrain features. The concept of cumulative danger index is used to select the best path for a penetrating hostile aircraft for any given pattern of placement. The aircraft is assumed to be intelligent and well-informed. The path is generated using a dynamic programming methodology. The software package so developed can be used off-line to choose the best among a number of possible battery placement patterns.

Linear programming approach for state estimation incorporating phasor measurements

This paper presents methodologies for incorporating phasor measurements into conventional state estimator. The angle measurements obtained from Phasor Measurement Units are handled as angle difference measurements rather than incorporating the angle measurements directly. Handling in such a manner overcomes the problems arising due to the choice of reference bus. Current measurements obtained from Phasor Measurement Units are treated as equivalent pseudo-voltage measurements at the neighboring buses. Two solution approaches namely normal equations approach and linear programming approach are presented to show how the Phasor Measurement Unit measurements can be handled. Comparative evaluation of both the approaches is also presented. Test results on IEEE 14 bus system are presented to validate both the approaches.

Convex Quadratic Programming Approach to the Maximum Matching Problem

The problem of determining a maximum matching or whether there exists a perfect matching, is very common in a large variety of applications and as been extensively studied in graph theory. In this paper we start to introduce a characterisation of a family of graphs for which its stability number is determined by convex quadratic programming. The main results connected with the recognition of this family of graphs are also introduced. It follows a necessary and sufficient condition which characterise a graph with a perfect matching and an algorithmic strategy, based on the determination of the stability number of line graphs, by convex quadratic programming, applied to the determination of a perfect matching. A numerical example for the recognition of graphs with a perfect matching is described. Finally, the above algorithmic strategy is extended to the determination of a maximum matching of an arbitrary graph and some related results are presented.

Design of B-spline neural networks using a bacterial programming approach

The design phase of B-spline neural networks represents a very high computational task. For this purpose, heuristics have been developed, but have been shown to be dependent on the initial conditions employed. In this paper a new technique, Bacterial Programming, is proposed, whose principles are based on the replication of the microbial evolution phenomenon. The performance of this approach is illustrated and compared with existing alternatives.

From embryonic stem cells to sensory hair cells : a programming approach

Tese de doutoramento, Ciências Biomédicas (Biologia do Desenvolvimento), Universidade de Lisboa, Faculdade de Medicina, 2014