reliable single chip genotyping with semi-parametric log-concave mixtures可靠的单芯片基因分型与semi-parametric log-concave混合物.pdfVIP

Reliable Single Chip Genotyping with Semi-Parametric Log-Concave Mixtures 1 2 3 Ralph C. A. Rippe *, Jacqueline J. Meulman , Paul H. C. Eilers 1 Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, 2 Institute of Mathematics, Leiden University, Leiden, The Netherlands, 3 Department of Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands Abstract The common approach to SNP genotyping is to use (model-based) clustering per individual SNP, on a set of arrays. Genotyping all SNPs on a single array is much more attractive, in terms of flexibility, stability and applicability, when developing new chips. A new semi-parametric method, named SCALA, is proposed. It is based on a mixture model using semi-parametric log-concave densities. Instead of using the raw data, the mixture is fitted on a two-dimensional histogram, thereby making computation time almost independent of the number of SNPs. Furthermore, the algorithm is effective in low-MAF situations. Comparisons between SCALA and CRLMM on HapMap genotypes show very reliable calling of single arrays. Some heterozygous genotypes from HapMap are called homozygous by SCALA and to lesser extent by CRLMM too. Furthermore, HapMap’s NoCalls (NN) could be genotyped by SCALA, mostly with high probability. The software is available as R scripts from the website www.math.leidenuniv.nl/,rrippe. Citation: Rippe RCA, Meulman JJ, Eilers PHC (2012) Reliable Single Chip Genotyping with Semi-Parametric Log-Concave Mixtures. PLoS ONE 7(10): e46267. doi:10.1371/journal.pone.0046267 Editor: Zhaoxia Yu, University of California, Irvine, United States of America Received May 1, 2012; Accepted August 31, 2012; Published October 16, 2012 Copyright: 2012 Rippe