Training Set (Reference)

1. Training Set (Reference) Probe selection based on dosage response. Compute mean intensity across selected probes for PMa and PMb separately Log transform probe intensity and standardization based on MM probes Intensity adjustment by regressing on fragment length and probe GC content Summarize mean and variance of PMa and PMb intensity for each SNP across sub-groups of individuals with same genotype Use training set intensity to estimate allele-specific and total CN. Summarize distribution of total CN of the training set at SNP level Estimate allele-specific CN models at individual SNP level Test Sample Intensity adjustment by regressing on fragment length and probe GC content Intensity adjustment by regressing on reference mean Log transform probe intensity and standardization based on MM probes Compute mean intensity across selected probes for PMa and PMb Compare total CN with the training set and derive significance. Estimate allele-specific and total CN Regression tree to partition the genome based on total CN. Average the CN and significance in each region Regression tree to further partition each region based on allele-specific CN • 100kb kernel smoothing on • allele-specific CN • total CN • total significance