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.

On the bottleneck linear programming problem

In this paper, the results on primal methods for Bottleneck Linear Programming (BLP) problem are briefly surveyed, the primal method is presented and the degenerate case related to Bottleneck Transportation Problem (BTP) is explicitly considered. The algorithm is based on the idea of using auxiliary coefficients as is done by Garfinkel and Rao [6]. The modification presented for the BTP rectifies the defect in Hammer's method in the case of degenerate basic feasible solution. Illustrative numerical examples are also given.

Finite field computation technique for exact solution of systems of linear equations and interval linear programming problems

An error-free computational approach is employed for finding the integer solution to a system of linear equations, using finite-field arithmetic. This approach is also extended to find the optimum solution for linear inequalities such as those arising in interval linear programming probloms.

A generalized Linear Programming based approach to optimal divisible load scheduling

In this paper we propose a general Linear Programming (LP) based formulation and solution methodology for obtaining optimal solution to the load distribution problem in divisible load scheduling. We exploit the power of the versatile LP formulation to propose algorithms that yield exact solutions to several very general load distribution problems for which either no solutions or only heuristic solutions were available. We consider both star (single-level tree) networks and linear daisy chain networks, having processors equipped with front-ends, that form the generic models for several important network topologies. We consider arbitrary processing node availability or release times and general models for communication delays and computation time that account for constant overheads such as start up times in communication and computation. The optimality of the LP based algorithms is proved rigorously.

An efficient algorithm for linear programming

A simple but efficient algorithm is presented for linear programming. The algorithm computes the projection matrix exactly once throughout the computation unlike that of Karmarkar’s algorithm where in the projection matrix is computed at each and every iteration. The algorithm is best suitable to be implemented on a parallel architecture. Complexity of the algorithm is being studied.

Positional Consensus of Multi-Agent Systems Using Linear Programming Based Decentralized Control with Rectilinear Decision Domain

In this paper we develop a Linear Programming (LP) based decentralized algorithm for a group of multiple autonomous agents to achieve positional consensus. Each agent is capable of exchanging information about its position and orientation with other agents within their sensing region. The method is computationally feasible and easy to implement. Analytical results are presented. The effectiveness of the approach is illustrated with simulation results.

Solving linear programming problems exactly

A linear programming problem in an inequality form having a bounded solution is solved error-free using an algorithm that sorts the inequalities, removes the redundant ones, and uses the p-adic arithmetic. (C) Elsevier Science Inc., 1997

Register Allocation and Optimal Spill code Scheduling in Software Pipelined Loops using 0-1 Integer Linear Programming Formulation

In achieving higher instruction level parallelism, software pipelining increases the register pressure in the loop. The usefulness of the generated schedule may be restricted to cases where the register pressure is less than the available number of registers. Spill instructions need to be introduced otherwise. But scheduling these spill instructions in the compact schedule is a difficult task. Several heuristics have been proposed to schedule spill code. These heuristics may generate more spill code than necessary, and scheduling them may necessitate increasing the initiation interval. We model the problem of register allocation with spill code generation and scheduling in software pipelined loops as a 0-1 integer linear program. The formulation minimizes the increase in initiation interval (II) by optimally placing spill code and simultaneously minimizes the amount of spill code produced. To the best of our knowledge, this is the first integrated formulation for register allocation, optimal spill code generation and scheduling for software pipelined loops. The proposed formulation performs better than the existing heuristics by preventing an increase in II in 11.11% of the loops and generating 18.48% less spill code on average among the loops extracted from Perfect Club and SPEC benchmarks with a moderate increase in compilation time.

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.

Design of logical topologies for wavelength-routed optical networks

his paper studies the problem of designing a logical topology over a wavelength-routed all-optical network (AON) physical topology, The physical topology consists of the nodes and fiber links in the network, On an AON physical topology, we can set up lightpaths between pairs of nodes, where a lightpath represents a direct optical connection without any intermediate electronics, The set of lightpaths along with the nodes constitutes the logical topology, For a given network physical topology and traffic pattern (relative traffic distribution among the source-destination pairs), our objective is to design the logical topology and the routing algorithm on that topology so as to minimize the network congestion while constraining the average delay seen by a source-destination pair and the amount of processing required at the nodes (degree of the logical topology), We will see that ignoring the delay constraints can result in fairly convoluted logical topologies with very long delays, On the other hand, in all our examples, imposing it results in a minimal increase in congestion, While the number of wavelengths required to imbed the resulting logical topology on the physical all optical topology is also a constraint in general, we find that in many cases of interest this number can be quite small, We formulate the combined logical topology design and routing problem described above (ignoring the constraint on the number of available wavelengths) as a mixed integer linear programming problem which we then solve for a number of cases of a six-node network, Since this programming problem is computationally intractable for larger networks, we split it into two subproblems: logical topology design, which is computationally hard and will probably require heuristic algorithms, and routing, which can be solved by a linear program, We then compare the performance of several heuristic topology design algorithms (that do take wavelength assignment constraints into account) against that of randomly generated topologies, as well as lower bounds derived in the paper.

Variable Elimination in Linear Constraints

Gauss and Fourier have together provided us with the essential techniques for symbolic computation with linear arithmetic constraints over the reals and the rationals. These variable elimination techniques for linear constraints have particular significance in the context of constraint logic programming languages that have been developed in recent years. Variable elimination in linear equations (Guassian Elimination) is a fundamental technique in computational linear algebra and is therefore quite familiar to most of us. Elimination in linear inequalities (Fourier Elimination), on the other hand, is intimately related to polyhedral theory and aspects of linear programming that are not quite as familiar. In addition, the high complexity of elimination in inequalities has forces the consideration of intricate specializations of Fourier's original method. The intent of this survey article is to acquaint the reader with these connections and developments. The latter part of the article dwells on the thesis that variable elimination in linear constraints over the reals extends quite naturally to constraints in certain discrete domains.

Qualitative theorem proving in linear constraints

We know, from the classical work of Tarski on real closed fields, that elimination is, in principle, a fundamental engine for mechanized deduction. But, in practice, the high complexity of elimination algorithms has limited their use in the realization of mechanical theorem proving. We advocate qualitative theorem proving, where elimination is attractive since most processes of reasoning take place through the elimination of middle terms, and because the computational complexity of the proof is not an issue. Indeed what we need is the existence of the proof and not its mechanization. In this paper, we treat the linear case and illustrate the power of this paradigm by giving extremely simple proofs of two central theorems in the complexity and geometry of linear programming.

Optimum Load Shedding Through Programming Techniques

This paper obtains a new accurate model for sensitivity in power systems and uses it in conjunction with linear programming for the solution of load-shedding problems with a minimum loss of loads. For cases where the error in the sensitivity model increases, other linear programming and quadratic programming models have been developed, assuming currents at load buses as variables and not load powers. A weighted error criterion has been used to take priority schedule into account; it can be either a linear or a quadratic function of the errors, and depending upon the function appropriate programming techniques are to be employed.

Extension of TSVM to multi-class and hierarchical text classification problems With general losses

Transductive SVM (TSVM) is a well known semi-supervised large margin learning method for binary text classification. In this paper we extend this method to multi-class and hierarchical classification problems. We point out that the determination of labels of unlabeled examples with fixed classifier weights is a linear programming problem. We devise an efficient technique for solving it. The method is applicable to general loss functions. We demonstrate the value of the new method using large margin loss on a number of multi-class and hierarchical classification datasets. For maxent loss we show empirically that our method is better than expectation regularization/constraint and posterior regularization methods, and competitive with the version of entropy regularization method which uses label constraints.