A fast top–down method for constructing reliable radiation hybrid frameworks

• Published in: Bioinformatics Vol. 18; no. 1; pp. 11 - 18
• Main Authors: Bø, Trond H., Jonassen, Inge, Eidhammer, Ingvar, Helgesen, Carsten
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-01-2002; Oxford Publishing Limited (England)
• Subjects: Algorithms; Biological and medical sciences; Chromosomes, Human - genetics; Computational Biology; Databases, Genetic; Fundamental and applied biological sciences. Psychology; General aspects; Genetic Markers; Humans; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); Radiation Hybrid Mapping - methods; Radiation Hybrid Mapping - statistics & numerical data; Contig; Genetic marker; Computer program; Radiation Hybrid Mapping; Graphical interface; Bioinformatics; Algorithm; Sequencing; Physical map
• ISSN: 1367-4803; 1460-2059; 1367-4811
• DOI: 10.1093/bioinformatics/18.1.11

Motivation: Radiation Hybrid Mapping (RHM) is a technique used to order a set of markers on a genome and estimating physical distances between them. RHM provides information on marker placement independent from other methods such as sequencing, and can therefore be used for example in genome sequencing to help ordering contigs. A radiation hybrid framework can be constructed by choosing a set of markers so that the chromosome coverage is good and so that the markers can be ordered with high confidence. Automatically constructing RHM frameworks is a computationally challenging problem. Results: We have developed a new method for constructing radiation hybrid frameworks. Given a relatively large set of markers for a chromosome, the algorithm aims to select an ordered subset that makes up a framework, and that contains as many markers as possible. The algorithm has a time complexity that is better than any of the existing methods that we are aware of. Furthermore, we propose a method for comparing if two frameworks are consistent, giving a visual presentation as well as quantitative measures of how well the two frameworks agree. Applying our method on marker sets from 22 human chromosomes and comparing the resulting frameworks with previously published frameworks, we demonstrate that our automatic method efficiently constructs frameworks with good coverage of each chromosome and with high degree of agreement on the marker ordering. Availability: The software is available from the authors. Supplementary information: MCST paths, frameworks and plots are available at http://www.ii.uib.no/~trondb/RHmapping/ Contact: [e-mail] * To whom correspondence should be addressed.