Andrei Gagarin

An efficient method for the detection and elimination of systematic error in high-throughput screening

MOTIVATION High-throughput screening (HTS) is an early-stage process in drug discovery which allows thousands of chemical compounds to be tested in a single study. We report a method for correcting HTS data prior to the hit selection process (i.e. selection of active compounds). The proposed correction minimizes the impact of systematic errors which may affect the hit selection in HTS. The introduced method, called a well correction, proceeds by correcting the distribution of measurements within wells of a given HTS assay. We use simulated and experimental data to illustrate the advantages of the new method compared to other widely-used methods of data correction and hit selection in HTS. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

HTS-Corrector: software for the statistical analysis and correction of experimental high-throughput screening data

MOTIVATION High-throughput screening (HTS) plays a central role in modern drug discovery, allowing for testing of >100,000 compounds per screen. The aim of our work was to develop and implement methods for minimizing the impact of systematic error in the analysis of HTS data. To the best of our knowledge, two new data correction methods included in HTS-Corrector are not available in any existing commercial software or freeware. RESULTS This paper describes HTS-Corrector, a software application for the analysis of HTS data, detection and visualization of systematic error, and corresponding correction of HTS signals. Three new methods for the statistical analysis and correction of raw HTS data are included in HTS-Corrector: background evaluation, well correction and hit-sigma distribution procedures intended to minimize the impact of systematic errors. We discuss the main features of HTS-Corrector and demonstrate the benefits of the algorithms.

Distributed hierarchical search for balanced energy consumption routing spanning trees in wireless sensor networks

We provide a new heuristic method approach to search for degree-balanced and small weight routing spanning trees in a network. The method is a modification of Kruskals minimum spanning tree search algorithm and is based on a distributed search by hierarchical clusters. It provides spanning trees with a lower maximum weighted degree, a bigger diameter, and can be used for balanced energy consumption routing in wireless sensor networks (WSNs). The method can be naturally implemented in parallel or as a simple locally distributed algorithm. Simulations for a realistic case scenario WSN are done based on the transmission energy matrix. The simulation results show that the proposed approach can extend the functional lifetime of a WSN in terms of sensor transmission energy by 3-4 times. We also show that the results can be further improved by using a preliminary clustering of the input network.

Using Clustering Techniques to Improve Hit Selection in High-Throughput Screening

A typical modern high-throughput screening (HTS) operation consists of testing thousands of chemical compounds to select active ones for future detailed examination. The authors describe 3 clustering techniques that can be used to improve the selection of active compounds (i.e., hits). They are designed to identify quality hits in the observed HTS measurements. The considered clustering techniques were first tested on simulated data and then applied to analyze the assay inhibiting Escherichia coli dihydrofo-late reductase produced at the HTS laboratory of McMaster University.

Engineering Algorithms for Workflow Satisfiability Problem with User-Independent Constraints

The workflow satisfiability problem (WSP) is a planning problem. Certain sub-classes of this problem have been shown to be fixed-parameter tractable. In this paper we develop an implementation of an algorithm for WSP that has been shown, in our previous paper, to be fixed-parameter for user-independent constraints. In a set of computational experiments, we compare our algorithm to an encoding of the WSP into a pseudo-Boolean SAT problem solved by the well-known solver SAT4J. Our algorithm solves all instances of WSP generated in our experiments, unlike SAT4J, and it solves many instances faster than SAT4J. For lightly constrained instances, SAT4J usually outperforms our algorithm.

Randomized algorithms and upper bounds for multiple domination in graphs and networks

We consider four different types of multiple domination and provide new improved upper bounds for the k- and k-tuple domination numbers. They generalize two classical bounds for the domination number and are better than a number of known upper bounds for these two multiple domination parameters. Also, we explicitly present and systematize randomized algorithms for finding multiple dominating sets, whose expected orders satisfy new and recent upper bounds. The algorithms for k- and k-tuple dominating sets are of linear time in terms of the number of edges of the input graph, and they can be implemented as local distributed algorithms. Note that the corresponding multiple domination problems are known to be NP-complete.

Algorithms for the workflow satisfiability problem engineered for counting constraints

The workflow satisfiability problem (WSP) asks whether there exists an assignment of authorized users to the steps in a workflow specification that satisfies the constraints in the specification. The problem is NP-hard in general, but several subclasses of the problem are known to be fixed-parameter tractable (FPT) when parameterized by the number of steps in the specification. In this paper, we consider the WSP with user-independent counting constraints, a large class of constraints for which the WSP is known to be FPT. We describe an efficient implementation of an FPT algorithm for solving this subclass of the WSP and an experimental evaluation of this algorithm. The algorithm iteratively generates all equivalence classes of possible partial solutions until, whenever possible, it finds a complete solution to the problem. We also provide a reduction from a WSP instance to a pseudo-Boolean (PB) SAT instance. We apply this reduction to the instances used in our experiments and solve the resulting PB SAT problems using SAT4J, a PB SAT solver. We compare the performance of our algorithm with that of SAT4J and discuss which of the two approaches would be more effective in practice.

Upper bounds for the bondage number of graphs on topological surfaces

Abstract The bondage number b ( G ) of a graph G is the smallest number of edges of G whose removal results in a graph having the domination number larger than that of G . We show that, for a graph G having the maximum vertex degree Δ ( G ) and embeddable on an orientable surface of genus h and a non-orientable surface of genus k , b ( G ) ≤ min { Δ ( G ) + h + 2 , Δ ( G ) + k + 1 } . This generalizes known upper bounds for planar and toroidal graphs, and can be improved for bigger values of the genera h and k by adjusting the proofs.

Distributed Search for Balanced Energy Consumption Spanning Trees in Wireless Sensor Networks

Sensor networks are commonly used for security and surveillance applications. As sensor nodes have limited battery paower, computing, and storage resources, the energy efficient security techniques are needed. We provide a new heuristic approach to search for balanced and small weight routing spanning trees in a network. The approach is a modification of Kruskals minimum spanning tree (MST) search algorithm and is based on a distributed search by hierarchical clusters. It provides spanning trees with a lower maximum degree, a bigger diameter and can be used for balanced energy consumption routing in wireless sensor networks (WSNs). The approach can be implemented in parallel as well as a simple locally distributed algorithm. Simulations of a realistic scenario WSN are done based on the transmission energy matrix. The simulation results show that the proposed approach can extend the functional lifetime of a WSN in 3-4 times in terms of sensor transmission energy. Possible preliminary clustering of the input network is considered as well.

Forbidden minors and subdivisions for toroidal graphs with no K3,3's

Abstract Forbidden minors and subdivisions for toroidal graphs are numerous. In contrast, the toroidal graphs with no K3,3s have a nice explicit structure and short lists of obstructions. For these graphs, we provide the complete lists of four forbidden minors and eleven forbidden subdivisions.