5 results on '"Besenbacher, Søren"'
Search Results
2. Identifying disease associated genes by network propagation.
- Author
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Yu Qian, Besenbacher, Søren, Mailund, Thomas, and Schierup, Mikkel Heide
- Abstract
Background: Genome-wide association studies have identified many individual genes associated with complex traits. However, pathway and network information have not been fully exploited in searches for genetic determinants, and including this information may increase our understanding of the underlying biology of common diseases. Results: In this study, we propose a framework to address this problem in a principled way, with the underlying hypothesis that complex disease operates through multiple connected genes. Associations inferred from GWAS are translated into prior scores for vertices in a protein-protein interaction network, and these scores are propagated through the network. Permutation is used to select genes that are guilty-by-association and thus consistently obtain high scores after network propagation. We apply the approach to data of Crohn’s disease and call candidate genes that have been reported by other independent GWAS, but not in the analysed data set. A prediction model based on these candidate genes show good predictive power as measured by Area Under the Receiver Operating Curve (AUC) in 10 fold cross-validations. Conclusions: Our network propagation method applied to a genome-wide association study increases association findings over other approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
3. A fast algorithm for genome-wide haplotype pattern mining.
- Author
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Besenbacher, Søren, Pedersen, Christian N. S., and Mailund, Thomas
- Subjects
- *
GENETIC research , *NUCLEOTIDES , *GENOMES , *ALGORITHMS , *MEDICAL genetics - Abstract
Background: Identifying the genetic components of common diseases has long been an important area of research. Recently, genotyping technology has reached the level where it is cost effective to genotype single nucleotide polymorphism (SNP) markers covering the entire genome, in thousands of individuals, and analyse such data for markers associated with a diseases. The statistical power to detect association, however, is limited when markers are analysed one at a time. This can be alleviated by considering multiple markers simultaneously. The Haplotype Pattern Mining (HPM) method is a machine learning approach to do exactly this. Results: We present a new, faster algorithm for the HPM method. The new approach use patterns of haplotype diversity in the genome: locally in the genome, the number of observed haplotypes is much smaller than the total number of possible haplotypes. We show that the new approach speeds up the HPM method with a factor of 2 on a genome-wide dataset with 5009 individuals typed in 491208 markers using default parameters and more if the pattern length is increased. Conclusion: The new algorithm speeds up the HPM method and we show that it is feasible to apply HPM to whole genome association mapping with thousands of individuals and hundreds of thousands of markers. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
4. Identifying disease associated genes by network propagation.
- Author
-
Qian Y, Besenbacher S, Mailund T, and Schierup MH
- Subjects
- Crohn Disease pathology, Genome-Wide Association Study, Humans, Interleukin-12 metabolism, ROC Curve, Signal Transduction genetics, Computational Biology, Crohn Disease genetics, Crohn Disease metabolism, Protein Interaction Maps
- Abstract
Background: Genome-wide association studies have identified many individual genes associated with complex traits. However, pathway and network information have not been fully exploited in searches for genetic determinants, and including this information may increase our understanding of the underlying biology of common diseases., Results: In this study, we propose a framework to address this problem in a principled way, with the underlying hypothesis that complex disease operates through multiple connected genes. Associations inferred from GWAS are translated into prior scores for vertices in a protein-protein interaction network, and these scores are propagated through the network. Permutation is used to select genes that are guilty-by-association and thus consistently obtain high scores after network propagation. We apply the approach to data of Crohn's disease and call candidate genes that have been reported by other independent GWAS, but not in the analysed data set. A prediction model based on these candidate genes show good predictive power as measured by Area Under the Receiver Operating Curve (AUC) in 10 fold cross-validations., Conclusions: Our network propagation method applied to a genome-wide association study increases association findings over other approaches.
- Published
- 2014
- Full Text
- View/download PDF
5. Whole genome association mapping by incompatibilities and local perfect phylogenies.
- Author
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Mailund T, Besenbacher S, and Schierup MH
- Subjects
- Cystic Fibrosis diagnosis, Humans, Phylogeny, Polymorphism, Single Nucleotide genetics, Chromosome Mapping methods, Cystic Fibrosis genetics, Cytochrome P-450 CYP2D6 genetics, DNA Mutational Analysis methods, Genetic Predisposition to Disease genetics, Linkage Disequilibrium genetics
- Abstract
Background: With current technology, vast amounts of data can be cheaply and efficiently produced in association studies, and to prevent data analysis to become the bottleneck of studies, fast and efficient analysis methods that scale to such data set sizes must be developed., Results: We present a fast method for accurate localisation of disease causing variants in high density case-control association mapping experiments with large numbers of cases and controls. The method searches for significant clustering of case chromosomes in the "perfect" phylogenetic tree defined by the largest region around each marker that is compatible with a single phylogenetic tree. This perfect phylogenetic tree is treated as a decision tree for determining disease status, and scored by its accuracy as a decision tree. The rationale for this is that the perfect phylogeny near a disease affecting mutation should provide more information about the affected/unaffected classification than random trees. If regions of compatibility contain few markers, due to e.g. large marker spacing, the algorithm can allow the inclusion of incompatibility markers in order to enlarge the regions prior to estimating their phylogeny. Haplotype data and phased genotype data can be analysed. The power and efficiency of the method is investigated on 1) simulated genotype data under different models of disease determination 2) artificial data sets created from the HapMap ressource, and 3) data sets used for testing of other methods in order to compare with these. Our method has the same accuracy as single marker association (SMA) in the simplest case of a single disease causing mutation and a constant recombination rate. However, when it comes to more complex scenarios of mutation heterogeneity and more complex haplotype structure such as found in the HapMap data our method outperforms SMA as well as other fast, data mining approaches such as HapMiner and Haplotype Pattern Mining (HPM) despite being significantly faster. For unphased genotype data, an initial step of estimating the phase only slightly decreases the power of the method. The method was also found to accurately localise the known susceptibility variants in an empirical data set--the DeltaF508 mutation for cystic fibrosis--where the susceptibility variant is already known--and to find significant signals for association between the CYP2D6 gene and poor drug metabolism, although for this dataset the highest association score is about 60 kb from the CYP2D6 gene., Conclusion: Our method has been implemented in the Blossoc (BLOck aSSOCiation) software. Using Blossoc, genome wide chip-based surveys of 3 million SNPs in 1000 cases and 1000 controls can be analysed in less than two CPU hours.
- Published
- 2006
- Full Text
- View/download PDF
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