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Numerical Algorithms for Mapping of Multiple Quantitative Trait Loci in Experimental Populations
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för teknisk databehandling. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Numerisk analys. (ndim)
2005 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Most traits of medical or economic importance are quantitative, i.e. they can be measured on a continuous scale. Strong biological evidence indicates that quantitative traits are governed by a complex interplay between the environment and multiple quantitative trait loci, QTL, in the genome. Nonlinear interactions make it necessary to search for several QTL simultaneously. This thesis concerns numerical methods for QTL search in experimental populations. The core computational problem of a statistical analysis of such a population is a multidimensional global optimization problem with many local optima. Simultaneous search for d QTL involves solving a d-dimensional problem, where each evaluation of the objective function involves solving one or several least squares problems with special structure. Using standard software, already a two-dimensional search is costly, and searches in higher dimensions are prohibitively slow.

Three efficient algorithms for evaluation of the most common forms of the objective function are presented. The computing time for the linear regression method is reduced by up to one order of magnitude for real data examples by using a new scheme based on updated QR factorizations. Secondly, the objective function for the interval mapping method is evaluated using an updating technique and an efficient iterative method, which results in a 50 percent reduction in computing time. Finally, a third algorithm, applicable to the imputation and weighted linear mixture model methods, is presented. It reduces the computing time by between one and two orders of magnitude.

The global search problem is also investigated. Standard software techniques for finding the global optimum of the objective function are compared with a new approach based on the DIRECT algorithm. The new method is more accurate than the previously fastest scheme and locates the optimum in 1-2 orders of magnitude less time. The method is further developed by coupling DIRECT to a local optimization algorithm for accelerated convergence, leading to additional time savings of up to eight times. A parallel grid computing implementation of exhaustive search is also presented, and is suitable e.g for verifying global optima when developing efficient optimization algorithms tailored for the QTL mapping problem.

Using the algorithms presented in this thesis, simultaneous search for at least six QTL can be performed routinely. The decrease in overall computing time is several orders of magnitude. The results imply that computations which were earlier considered impossible are no longer difficult, and that genetic researchers thus are free to focus on model selection and other central genetical issues.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis , 2005. , s. 61
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 133
Emneord [en]
Scientific computing
HSV kategori
Forskningsprogram
Beräkningsvetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-6248ISBN: 91-554-6427-0 (tryckt)OAI: oai:DiVA.org:uu-6248DiVA, id: diva2:167517
Disputas
2006-01-13, Room 2446, Polacksbacken, Lägerhyddsvägen 2D, Uppsala, 10:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2005-12-22 Laget: 2005-12-22 Sist oppdatert: 2018-01-13bibliografisk kontrollert
Delarbeid
1. Efficient algorithms for quantitative trait loci mapping problems
Åpne denne publikasjonen i ny fane eller vindu >>Efficient algorithms for quantitative trait loci mapping problems
2002 (engelsk)Inngår i: Journal of Computational Biology, ISSN 1066-5277, E-ISSN 1557-8666, Vol. 9, s. 793-804Artikkel i tidsskrift (Fagfellevurdert) Published
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-67952 (URN)10.1089/10665270260518272 (DOI)12614547 (PubMedID)
Tilgjengelig fra: 2008-07-05 Laget: 2008-07-05 Sist oppdatert: 2018-01-10bibliografisk kontrollert
2. Simultaneous search for multiple QTL using the global optimization algorithm DIRECT
Åpne denne publikasjonen i ny fane eller vindu >>Simultaneous search for multiple QTL using the global optimization algorithm DIRECT
2004 (engelsk)Inngår i: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 20, s. 1887-1895Artikkel i tidsskrift (Fagfellevurdert) Published
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-67950 (URN)10.1093/bioinformatics/bth175 (DOI)15044246 (PubMedID)
Merknad

An efficient algorithm for solving least-squares problems with a specific structure is combined with an extended algorithm for global optimization. The scheme is applied to problems in genetics, where the solution can be computed several orders of magnitude faster than with previous methods.

Tilgjengelig fra: 2007-02-20 Laget: 2007-02-20 Sist oppdatert: 2018-01-10bibliografisk kontrollert
3. Efficient algorithms for multidimensional global optimization in genetic mapping of complex traits
Åpne denne publikasjonen i ny fane eller vindu >>Efficient algorithms for multidimensional global optimization in genetic mapping of complex traits
2010 (engelsk)Inngår i: Advances and Applications in Bioinformatics and Chemistry, ISSN 1178-6949, Vol. 3, s. 75-88Artikkel i tidsskrift (Fagfellevurdert) Published
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-93884 (URN)10.2147/AABC.S9240 (DOI)
Prosjekter
eSSENCE
Tilgjengelig fra: 2005-12-22 Laget: 2005-12-22 Sist oppdatert: 2018-01-13bibliografisk kontrollert
4. Efficient evaluation of the residual sum of squares for quantitative trait locus models in the case of complete marker genotype information
Åpne denne publikasjonen i ny fane eller vindu >>Efficient evaluation of the residual sum of squares for quantitative trait locus models in the case of complete marker genotype information
2005 (engelsk)Rapport (Annet vitenskapelig)
Serie
Technical report / Department of Information Technology, Uppsala University, ISSN 1404-3203 ; 2005-033
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-76701 (URN)
Tilgjengelig fra: 2007-02-04 Laget: 2007-02-04 Sist oppdatert: 2018-01-13bibliografisk kontrollert
5. Using parallel computing and grid systems for genetic mapping of quantitative traits
Åpne denne publikasjonen i ny fane eller vindu >>Using parallel computing and grid systems for genetic mapping of quantitative traits
2007 (engelsk)Inngår i: Applied Parallel Computing: State of the Art in Scientific Computing, Berlin: Springer-Verlag , 2007, s. 627-636Konferansepaper, Publicerat paper (Fagfellevurdert)
sted, utgiver, år, opplag, sider
Berlin: Springer-Verlag, 2007
Serie
Lecture Notes in Computer Science ; 4699
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-11546 (URN)10.1007/978-3-540-75755-9_76 (DOI)000250904900076 ()978-3-540-75754-2 (ISBN)
Tilgjengelig fra: 2007-09-26 Laget: 2007-09-26 Sist oppdatert: 2018-01-12bibliografisk kontrollert

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