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Local false discovery rate and minimum total error rate approaches to identifying interesting chromosomal regions

The simultaneous testing of a large number of hypotheses in a genome scan, using individual thresholds for significance, inherently leads to inflated genome-wide false positive rates. There exist various approaches to approximating the correct genomewide p-values under various assumptions, either by...

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Detalles Bibliográficos
Autores principales: Sinha, Ritwik, Sinha, Moumita, Mathew, George, Elston, Robert C, Luo, Yuqun
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866763/
https://www.ncbi.nlm.nih.gov/pubmed/16451632
http://dx.doi.org/10.1186/1471-2156-6-S1-S23
Descripción
Sumario:The simultaneous testing of a large number of hypotheses in a genome scan, using individual thresholds for significance, inherently leads to inflated genome-wide false positive rates. There exist various approaches to approximating the correct genomewide p-values under various assumptions, either by way of asymptotics or simulations. We explore a philosophically different criterion, recently proposed in the literature, which controls the false discovery rate. The test statistics are assumed to arise from a mixture of distributions under the null and non-null hypotheses. We fit the mixture distribution using both a nonparametric approach and commingling analysis, and then apply the local false discovery rate to select cut-off points for regions to be declared interesting. Another criterion, the minimum total error, is also explored. Both criteria seem to be sensible alternatives to controlling the classical type I and type II error rates.