System and method for genotype analysis and enhanced monte carlo simulation method to estimate misclassification rate in automated genotyping

Abstract

The present invention relates to methods and systems for the analysis of the dissociation behavior of nucleic acids. The present invention includes methods and systems for analyzing dynamic profiles of genotypes of nucleic acids, including the steps of using a computer, including a processor and a memory, to convert dynamic profiles of known genotypes of a nucleic acid to multi-dimensional data points, wherein the dynamic profiles each comprise measurements of a signal representing a physical change of a nucleic acid containing the known genotype relative to an independent variable; using the computer to reduce the multi-dimensional data points into reduced-dimensional data points; and generating a plot of the reduced-dimensional data points for each genotype. The present invention also relates to methods and systems for calculating error statistics for an assay for identifying a genotype in a biological sample using an enhanced Monte Carlo simulation method to generate a set of N random data points for each known genotype within a class of known genotypes, where each set of N random data points has the same mean data point and covariance matrix as a data set for each of the known genotypes.

1 . A method of analyzing dynamic profiles of genotypes of nucleic acids, the method comprising:
 using a computer, including a processor and a memory, to convert dynamic profiles of known genotypes of a nucleic acid to multi-dimensional data points, wherein the dynamic profiles each comprise measurements of a signal representing a physical change of a nucleic acid containing the known genotype relative to an independent variable;   using the computer to reduce the multi-dimensional data points into reduced-dimensional data points;   generating a plot of the reduced-dimensional data points for each genotype.   
     
     
         2 - 15 . (canceled) 
     
     
         16 . A method of determining the identity of a genotype of a nucleic acid present in a biological sample, comprising:
 (a) generating a dynamic profile of an unknown genotype contained in the biological sample, wherein the dynamic profile comprises measurements of a signal representing a physical change of a nucleic acid containing the unknown genotype relative to an independent variable;   (b) using a computer including a processor and a memory to compare the dynamic profile of the unknown genotype with an average dynamic profile of each known genotype in a class of known genotypes to generate a multi-dimensional data point, wherein the average dynamic profile of a known genotype comprises average measurements of a signal representing the physical change of a nucleic acid containing the known genotype relative to the independent variable and wherein the elements of the reduced-dimensional data point are correlation coefficients between the dynamic profile of the unknown genotype and the average dynamic profile for each known genotype in the class of genotypes;   (c) transforming the multi-dimensional data point to a reduced-dimensional data point; and   (d) generating a plot showing the reduced-dimensional data point for the unknown genotype.   
     
     
         17 - 18 . (canceled) 
     
     
         19 . A system for analyzing dynamic profiles of genotypes of nucleic acids, comprising:
 a computer, including a processor and a memory;   a conversion module configured to convert dynamic profiles of known genotypes of a nucleic acid to multi-dimensional data points, wherein the dynamic profiles each comprise measurements of a signal representing a physical change of a nucleic acid containing the known genotype relative to an independent variable;   a reduction module configured to reduce the multi-dimensional data points into reduced-dimensional data points;   a display device; and   a plotting module, configured to generate a plot of the reduced-dimensional data points for each genotype on the display device.   
     
     
         20 - 56 . (canceled)