PubMed Health⌕ Search

Biomedical subjects

Nusrat Rabbee

Publications and source records attributed to Nusrat Rabbee.

3 recordsLinked to original sources

A genotype calling algorithm for affymetrix SNP arrays.

MOTIVATION: A classification algorithm, based on a multi-chip, multi-SNP approach is proposed for Affymetrix SNP arrays. Current procedures for calling genotypes on SNP arrays process all the features associated with one chip and one SNP at a time. Using a large training sample where the genotype labels are known, we develop a supervised learning algorithm to obtain more accurate classification results on new data. The method we propose, RLMM, is based on a robustly fitted, linear model and uses the Mahalanobis distance for classification. The chip-to-chip non-biological variance is reduced through normalization. This model-based algorithm captures the similarities across genotype groups and probes, as well as across thousands of SNPs for accurate classification. In this paper, we apply RLMM to Affymetrix 100 K SNP array data, present classification results and compare them with genotype calls obtained from the Affymetrix procedure DM, as well as to the publicly available genotype calls from the HapMap project.

Algorithms↗

Power calculations for familial aggregation studies.

Family studies are frequently undertaken as the first step in the search for genetic determinants of disease. Significant familial aggregation of disease is suggestive of a genetic etiology for the disease, and may lead to more focused genetic analyses. Many methods have been proposed in the literature for the analysis of family studies. One model that is appealing for its simplicity of computation and the conditional interpretation of its parameters is the quadratic exponential model (e.g., Zhao and Prentice [1990] Biometrika 77:642-648; Betensky and Whittemore [1996] Appl. Stat. 45:422-429; Hudson et al. [2001a] Am. J. Epidemiol. 153:500-514). However, a limiting factor in its application, as well as that of the other proposed methods, is that power and sample size calculations have not been derived. These calculations are essential for investigators who are designing family studies. Here we derive analytic approximations for power for testing for familial aggregation, for both randomly sampled and nonrandomly sampled families. We also present simulation studies of power for both single- and two-disease cases, both under random and nonrandom sampling.

Breast Neoplasms↗

Power calculations for selective genotyping in QTL mapping in backcross mice.

Selective genotyping concerns the genotyping of a portion of individuals chosen on the basis of their phenotypic values. Often individuals are selected for genotyping from the high and low extremes of the phenotypic distribution. This procedure yields savings in cost and time by decreasing the total number of individuals genotyped. Previous work by Darvasi et al. (1993) has shown that the power to detect a QTL by genotyping 40-50 % of a population is roughly equivalent to genotyping the entire sample. However, these power studies have not accounted for different strategies of analysing the data when phenotypes of individuals in the middle are excluded, nor have they investigated the genome-wide type I error rate under these different strategies or different selection percentages. Further, these simulation studies have not considered markers over the entire genome. In this paper, we present simulation studies of power for the maximum likelihood approach to QTL mapping by Lander & Botstein (1989) in the context of selective genotyping. We calculate the power of selectively genotyping the individuals from the middle of the phenotypic distribution when performing QTL mapping over the whole mouse genome.

Animals↗