System, method, and computer software for genotyping analysis and identification of allelic imbalance
View Patent ↗Methods, systems and computer software products are provided for determining genotype of a sample using a plurality of probes. In one preferred embodiment, a tentative genotype call is made based upon the relative allele signals. Pattern recognition is then used to validate the tentative call.
1. A method for determining a change of genotype between two samples from an individual, comprising:
receiving a first genotyping data value and a second genotyping data value, wherein the first and second genotyping data values are calculated using a plurality of probe intensity values and each correlate with a genotype call selected from the group consisting of a heterozygous genotype call and a homozygous genotype call;
calculating a difference value using the first genotyping data value and the second genotyping data value; and
determining a change of genotype call, wherein the change of genotype call is true when the first genotyping data value correlates with the heterozygous genotype call and the second genotyping data value correlates with the homozygous genotype call and the difference value is greater than a threshold value.
2. The method of claim 1 , wherein:
the first genotyping value is calculated using probe intensities associated with a reference sample.
3. The method of claim 1 , wherein:
the second genotyping value is calculated using probe intensities associated with an experimental sample.
4. The method of claim 1 , wherein:
each of the first and second genotyping data values include a relative allele signal value.
5. The method of claim 1 , wherein:
the first genotyping data value correlates to the heterozygous genotype call when it is greater than 0.25 and less than 0.75.
6. The method of claim 1 , wherein:
the difference value is equal to the absolute value of the first genotyping data value minus the second genotyping data value.
7. The method of claim 1 , wherein:
the second genotyping data value correlates to the homozygous genotype call when it is less than 0.25 and greater than 0.75.
8. The method of claim 1 , wherein:
the threshold value is equal to 0.2.
9. The method of claim 1 , wherein:
the first and second genotyping data values are calculated using probe intensities from a probe set.
10. The method of claim 1 , wherein:
the difference value includes a normalized difference value.
11. The method of claim 10 , wherein:
the normalized difference value accounts for variability between a plurality of probes and one or more probe sets.
12. The method of claim 1 , wherein:
the true change of genotype call includes a loss of heterozygosity call.
13. A system for determining a change of genotype between two samples from an individual, comprising:
a computer to receive a first genotyping data value and a second genotyping data value, wherein the first and second genotype data values are calculated using a plurality of probe intensity values and each correlate with a genotype call selected from the group consisting of a heterozygous genotype call and a homozygous genotype call; and
a computer software program product to execute on the computer the method of calculating a difference value using the first genotyping data value and the second genotyping data value; and determining a change of genotype call, wherein the change of genotype call is true when the first genotyping data value correlates with the heterozygous genotype call and the second genotyping data value correlates with the homozygous genotype call and the difference value is greater than a threshold value.
14. The method of claim 1 , wherein:
the probe intensities are associated with a plurality of probes disposed upon a substrate.
15. The method of claim 14 , wherein:
the substrate is selected from the group consisting of optical fibers and beads.