Computer-aided probability base calling for arrays of nucleic acid probes on chips

• US 6,228,593 B1
• Filed: 01/14/2000
• Issued: 05/08/2001
• Est. Priority Date: 09/14/1995
• Status: Expired due to Term

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Lipshutz, Robert J., Walker, Michael G.
• Primary Examiner(s): Brusca, John S.
• Assistant Examiner(s): SIU, STEPHEN C
• Application Number:
  US09/483,190
• Time in Patent Office: 480 Days
• Field of Search: 435/6, 435/7.92, 435/973, 935/6, 935/7.92, 935/973, 935/88, 536/23.1
• US Class Current: 506/8
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: Y10S 435/973 Simultaneous determination of more than one analyte

Abstract

A computer system for analyzing nucleic acid sequences is provided. The computer system is used to calculate probabilities for determining unknown bases by analyzing the fluorescence intensities of hybridized nucleic acid probes on biological chips. Additionally, information from multiple experiments is utilized to improve the accuracy of calling unknown bases.

Claims

1. A computer implemented method of calling an unknown base in a sample nucleic acid sequence, comprising:

inputting a plurality of base calls for the unknown base, each of the base calls having an associated value;

selecting a base call from the plurality of base calls for the unknown base according to the associated values; and

calling the unknown base according to the selected base call.

2. The method of claim 1, wherein the value represents a confidence that the unknown base is called correctly.

3. The method of claim 1, wherein the value represents a hybridization probe intensity.

4. The method of claim 1, wherein the selected base call has the highest associated value.

5. The method of claim 1, further comprising performing a base call of the unknown base according to hybridization of nucleic acid probes with the sample nucleic acid sequence.

6. The method of claim 1, wherein the base calls are determined from a plurality of experiments.

7. A computer program that calls an unknown base in a sample nucleic acid sequence, comprising:

code that receives as input a plurality of base calls for the unknown base, each of the base calls having an associated value;

code that selects a base call from the plurality of base calls for the unknown base according to the associated values; and

code that calls the unknown base according to the selected base call;

wherein the codes are stored on a tangible medium.

8. The computer program of claim 7, wherein the value represents a confidence that the unknown base is called correctly.

9. The computer program of claim 7, wherein the value represents a hybridization probe intensity.

10. The computer program of claim 7, wherein the selected base call has the highest associated value.

11. The computer program of claim 7, further comprising code that performs a base call of the unknown base according to hybridization of nucleic acid probes with the sample nucleic acid sequence.

12. The computer program of claim 7, wherein the base calls are determined from a plurality of experiments.

13. A system that calls an unknown base in a sample nucleic acid sequence, comprising:

a processor; and

a computer readable medium coupled to the processor, said computer readable medium storing a computer program comprising;

code that receives as input a plurality of base calls for the unknown base, each of the base calls having an associated value;

code that selects a base call from the plurality of base calls for the unknown base according to the associated values; and

code that calls the unknown base according to the selected base call.

14. The system of claim 13, wherein the value represents a confidence that the unknown base is called correctly.

15. The system of claim 13, wherein the value represents a hybridization probe intensity.

16. The system of claim 13, wherein the selected base call has the highest associated value.

17. The system of claim 13, further comprising code that performs a base call of the unknown base according to hybridization of nucleic acid probes with the sample nucleic acid sequence.

18. A The system of claim 13, wherein the base calls are determined from a plurality of experiments.