Method and System for Genotyping Samples in a Normalized Allelic Space
AssigneeLife Technologies Corporation
InventorsMark R. Pratt, David Holden
Life of this patent
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Abstract
Aspects of the present invention describe an apparatus and method for generating genotype calls for a sample. The genotyping initially models allelic signal response into an allelic model having one or more model parameters for an identified one or more sources of systematic variation. The model and parameters are then used to transform the allelic signals to a normalized normalized allelic space that serves to compensate for the one or more sources of systematic variation. By compensating for the systematic variation in this manner, the genotype for the sample is readily determined based upon its relationship to the representation of the allelic signals in normalized allelic space and in accordance with the allelic model.
Claims17
A computer implemented method of generating genotype calls for a sample comprising:
- modeling allelic signal response into an allelic model having one or more model parameters for an identified one or more sources of systematic variation;
- transforming the allelic signals through the one or more model parameters of the allelic model to a normalized allelic space that serves to compensate for the one or more sources of systematic variation;
- determining a genotype for the sample based upon its relationship to the representation of the allelic signals in normalized allelic space and in accordance with the allelic model.
- creating a fixed prior probability distribution of normalized allele signals from a statistically significant training set of genotype data by fitting a normalized training set of genotype data to probability distributions that reflect a set of allowed genotypes in the normalized allelic space;
- transforming ordinary allelic signals through the one or more model parameters of an allelic model to a normalized allelic space that serves to compensate for the one or more sources of systematic variation;
- and
- calling the genotype for the sample based upon a greatest prior probability as reflected by the fitted probability distribution and applied to the sample normalized in the normalized allelic space.
A computer program product for generating genotype calls for a sample, comprising instructions operable to cause a programmable processor to:
- model allelic signal response into an allelic model having one or more model parameters for an identified one or more sources of systematic variation;
- transform the allelic signals through the one or more model parameters of the allelic model to a normalized allelic space that serves to compensate for the one or more sources of systematic variation;
- determine a genotype for the sample based upon its relationship to the representation of the allelic signals in normalized allelic space and in accordance with the allelic model;
- measure a Cartesian distance from a sample represented in the normalized allelic space to an expected one or more genotype coordinates;
- and
- call a genotype for the sample that represents the shortest measured Cartesian distance between the sample and one of the expected one or more genotype coordinates.
An apparatus for generating genotype calls for a sample, comprising:
- means for modeling allelic signal response into an allelic model having one or more model parameters for an identified one or more sources of systematic variation;
- means for transforming the allelic signals through the one or more model parameters of the allelic model to a normalized allelic space that serves to compensate for the one or more sources of systematic variation;
- and
- means for determining a genotype for the sample according to a clustering of allelic data signals as represented in the normalized allelic space;
- means for measuring a relative angular offset of values for the allelic data signals in the normalized allelic space;
- and
- means for calling a genotype for the sample based upon its proximity to the different angular offsets of values and their corresponding genotype classifications.
Dependencies are inferred from the claim text.