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 plurality of probe intensity values;
calculating a first genotyping data value and a second genotyping data value using one or more of the probe intensity values associated with a first strand and one or more of the probe intensity values associated with a second strand;
calculating a difference value using the first genotyping data value and the second genotyping data value;
normalizing the difference value using a normalization value for the first strand and a normalization value for the second strand; and
determining a change of genotype call, wherein the change of genotype call is true when the first genotyping data value correlates with a heterozygous genotype call and the second genotyping data value correlates with a homozygous genotype call and the normalized difference value is greater than a threshold value.
2. The method of claim 1 , further comprising:
displaying an indication of a disease condition or state, wherein the indication is displayed when the change of genotype call is true.
3. The method of claim 2 , wherein:
the indication of a disease condition or state is displayed in a graphical user interface.
4. The method of claim 2 , wherein:
the graphical user interface comprises graphical elements to display the indication.
5. The method of claim 2 , wherein:
the graphical user interface comprises textual elements to display the indication.
6. The method of claim 2 , wherein:
the graphical user interface comprises graphical and textual elements to display the indication.
7. The method of claim 1 , wherein:
each of the normalization values comprise a standard deviation value.
8. The method of claim 1 , wherein:
the first and second genotyping data values are calculated using the probe intensities associated with samples from the individual.
9. The method of claim 1 , wherein:
the first strand comprises a coding strand, and the second strand comprises a non-coding strand.
10. A system for determining a change of genotype between two samples from an individual, comprising:
a computer that receives a plurality of probe intensity values;
a computer software program product to execute on the computer the method of calculating a first genotyping data value and a second genotyping data value using one or more of the probe intensity values associated with a first strand and one or more of the probe intensity values associated with a second strand; calculating a difference value using the first genotyping data value and the second genotyping data value; normalizing the difference value using a normalization value for the first strand and a normalization value for the second strand; and determining a change of genotype call, wherein the change of genotype call is true when the first genotyping data value correlates with a heterozygous genotype call and the second genotyping data value correlates with a homozygous genotype call and the normalized difference value is greater than a threshold value.
11. The system of claim 10 , wherein:
the computer software program product further executes the method of displaying an indication of a disease condition or state, wherein the indication is displayed when the change of genotype call is true.
12. The system of claim 11 , wherein:
the indication of a disease condition or state is displayed in a graphical user interface.
13. The system of claim 12 , wherein:
the graphical user interface comprises graphical elements to display the indication.
14. The system of claim 12 , wherein:
the graphical user interface comprises textual elements to display the indication.
15. The system of claim 12 , wherein:
the graphical user interface comprises graphical and textual elements to display the indication.
16. The system of claim 10 , wherein:
each of the normalization values comprise a standard deviation value.
17. The system of claim 10 , wherein:
the first and second genotyping data values are calculated using the probe intensities associated with samples from the individual.
18. The system of claim 10 , wherein:
the first strand comprises a coding strand, and the second strand comprises a non-coding strand.
19. A system for determining a change of genotype between two samples from an individual, comprising:
a scanner that acquires a plurality of probe intensity values from one or more probe arrays;
a computer that receives the plurality of probe intensity values;
a computer software program product to execute on the computer the method of calculating a first genotyping data value and a second genotyping data value using one or more of the probe intensity values associated with a first strand and one or more of the probe intensity values associated with a second strand; calculating a difference value using the first genotyping data value and the second genotyping data value; normalizing the difference value using a normalization value for the first strand and a normalization value for the second strand; and determining a change of genotype call, wherein the change of genotype call is true when the first genotyping data value correlates with a heterozygous genotype call and the second genotyping data value correlates with a homozygous genotype call and the normalized difference value is greater than a threshold value.
20. The system of claim 19 , wherein:
the computer software program further executes the method of displaying an indication of a disease condition or state, wherein the indication is displayed when the change of genotype call is true.