We have developed a novel algorithm for cluster analysis that is based on graph theoretic techniques. A similarity graph is defined and clusters in that graph correspond to highly connected subgraphs. A polynomial algorithm to compute them efficiently is presented. Our algorithm produces a clustering with some provably good properties. The application that motivated this study was gene expression analysis, where a collection of cDNAs must be clustered based on their oligonucleotide fingerprints. The algorithm has been tested intensively on simulated libraries and was shown to outperform extant methods. It demonstrated robustness to high noise levels. In a blind test on real cDNA fingerprint data the algorithm obtained very good results. Utilizing the results of the algorithm would have saved over 70% of the cDNA sequencing cost on that data set. 1 Introduction Cluster analysis seeks grouping of data elements into subsets, so that elements in the same subset are in some sense more cl...

Motivation: Image analysis is a major part of data evaluation for array hybridization experiments in molecular biology. The program presented here is designed to analyze automatically images from hybridization experiments with various arrangements: different kinds of probes (oligonucleotides or complex probes), different supports (nylon filters or glass slides), different labeling of probes (radioactively or fluorescently). The program is currently applied to oligonucleotide fingerprinting projects and complex hybridizations. The only precondition for the use of the program is that the targets are arrayed in a grid, which can be approximately transformed to an orthogonal equidistant grid by a projective mapping. Results: We demonstrate that our program can cope with the following problems: global distortion of the grid, missing of grid nodes, local deviation of the spot from its specified grid position. This is checked by different quality measures. The image analysis of oligonucleotide fingerprint experiments on an entire genetic library is used, in clustering procedures, to group related clones together. The results show that the program yields automatically generated high quality input data for follow up analysis such as clustering procedures. Availability: The executable files will be available upon request for academics. Contact: steinfat@molgen.mpg.de

We propose two efficient heuristics for minimizing the number of oligonucleotide probes needed for analyzing populations of ribosomal RNA gene (rDNA) clones by hybridization experiments on DNA microarrays. Such analyses have applications in the study of microbial communities. Unlike in the classical SBH (sequencing by hybridization) procedure, where multiple probes are on a DNA chip, in our applications we perform a series of experiments, each one consisting of applying a single probe to a DNA microarray containing a large sample of rDNA sequences from the studied population. The overall cost of the analysis is thus roughly proportional to the number of experiments, underscoring the need for minimizing the number of probes. Our algorithms are based on two well-known optimization techniques, i.e. simulated annealing and Lagrangian relaxation, and our preliminary tests demonstrate that both algorithms are able to find satisfactory probe sets for real rDNA data.

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this document we will briefly discuss several topics:

One of the first steps in characterizing an ecosystem is to describe the organisms inhabiting it. For microbial studies, experimental limitations have hindered the ability to depict diverse communities. Here we describe oligonucleotide fingerprinting of rRNA genes (OFRG), a method that permits identification of arrayed rRNA genes (rDNA) through a series of hybridization experiments using small DNA probes. To demonstrate this strategy, we examined the bacteria inhabiting two different soils. Analysis of 1,536 rDNA clones revealed 766 clusters grouped into five major taxa: Bacillus, Actinobacteria, Proteobacteria, and two undefined assemblages. Soil-specific taxa were identified and then independently confirmed through cluster-specific PCR of the original soil DNA. Near-species-level resolution was obtained by this analysis as clones with average sequence identities of 97 % were grouped in the same cluster. A comparison of these OFRG results with the results obtained in a denaturing gradient gel electrophoresis analysis of the same two soils demonstrated the significance of this methodological advance. OFRG provides a cost-effective means to extensively analyze microbial communities and should have applications in medicine, biotechnology, and ecosystem studies. How diverse are microbial communities? Does microbial diversity lead to ecosystem stability? What are the relationships between microbial community composition and ecosystem

We consider the following clustering problems: given a general undirected graph, partition its vertices into disjoint clusters such that each cluster forms a clique and the number of edges within the clusters is maximized (Max-ECP), or the number of edges between clusters is minimized (Min-ECP). These problems arise naturally in the DNA clone classification. We investigate the hardness of finding such partitions and provide approximation algorithms. Further, we show that greedy strategies yield constant factor approximations for graph classes for which maximum cliques can be found e#ciently.

Abstract. DNA microarrays are widely used techniques in molecular biology and DNA computing area. It consists of the DNA sequences called probes, which are DNA complementaries to the genes of interest, on solid surfaces. And its reliability seriously depends on the quality of the probe sequences. Therefore, one must carefully choose the probe sets in target sequences. In this paper, the probe design for DNA microarrays is formulated as the multi-objective optimization problem. We propose a multi-objective evolutionary approach, which is known to be suitable for this kind of optimization problem. Since a multi-objective evolutionary algorithm can find multiple solutions at a time, we used thermodynamic criteria to choose the most suitable one. For the experiments, the probe set generated by the proposed method is compared to the sequences used in commercial microarrays, which detects a set of Human Papillomavirus (HPV). The comparison result supports that our approach can be useful to optimize probe sequences. Contents Area: Bioinformatics and AI, Evolutionary computing 1

Abstract—Probe design is one of the most important tasks in successful deoxyribonucleic acid microarray experiments. We propose a multiobjective evolutionary optimization method for oligonucleotide probe design based on the multiobjective nature of the probe design problem. The proposed multiobjective evolutionary approach has several distinguished features, compared with previous methods. First, the evolutionary approach can find better probe sets than existing simple filtering methods with fixed threshold values. Second, the multiobjective approach can easily incorporate the user’s custom criteria or change the existing criteria. Third, our approach tries to optimize the combination of probes for the given set of genes, in contrast to other tools that independently search each gene for qualifying probes. Lastly, the multiobjective optimization method provides various sets of probe combinations, among which the user can choose, depending on

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