title: Optimal genotype determination in highly multiplexed SNP data.
abstract: High-throughput genotyping technologies that enable large association studies are already available. Tools for genotype determination starting from raw signal intensities need to be automated, robust, and flexible to provide optimal genotype determination given the specific requirements of a study. The key metrics describing the performance of a custom genotyping study are assay conversion, call rate, and genotype accuracy. These three metrics can be traded off against each other. Using the highly multiplexed Molecular Inversion Probe technology as an example, we describe a methodology for identifying the optimal trade-off. The methodology comprises: a robust clustering algorithm and assessment of a large number of data filter sets. The clustering algorithm allows for automatic genotype determination. Many different sets of filters are then applied to the clustered data, and performance metrics resulting from each filter set are calculated. These performance metrics relate to the power of a study and provide a framework to choose the most suitable filter set to the particular study.
authors.affiliation: ParAllele BioScience, South San Francisco, CA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Moorhead
authors.forename: Paul
authors.initials: P
authors.lastname: Hardenbol
authors.forename: Farooq
authors.initials: F
authors.lastname: Siddiqui
authors.forename: Matthew
authors.initials: M
authors.lastname: Falkowski
authors.forename: Carsten
authors.initials: C
authors.lastname: Bruckner
authors.forename: James
authors.initials: J
authors.lastname: Ireland
authors.forename: Hywel B
authors.initials: HB
authors.lastname: Jones
authors.forename: Maneesh
authors.initials: M
authors.lastname: Jain
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Willis
authors.forename: Malek
authors.initials: M
authors.lastname: Faham
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D003198:Computer Simulation; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D015336:Molecular Probe Techniques; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D012107:Research Design
chemical_list: D005819:Genetic Markers