METHODS FOR COMPUTING POSITIONAL BASE PROBABILITIES USING EXPERMINENTALS BASE VALUE DISTRIBUTIONS

• US 20080221832A1
• Filed: 11/09/2007
• Published: 09/11/2008
• Est. Priority Date: 11/09/2006
• Status: Abandoned Application

• Current Assignee: Complete Genomics Incorporated (BGI Genomics Co., Ltd.)
• Original Assignee: Complete Genomics Incorporated (BGI Genomics Co., Ltd.)
• Inventors: Drmanac, Radoje
• Application Number:
  US11/938,221
• Publication Number:
  US 20080221832A1
• Time in Patent Office: Days
• US Class Current: 702/181
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: G16B 30/20 Sequence assembly

Abstract

Aspects of the various embodiments of the invention relate generally to computing relative base value probabilities using discrete experimental base values to calculate distributions of relative base probabilities. This information can be used with associated experimental measurements to increase the accuracy of the data analysis.

Claims

1. A method for determining a relative base probability, comprising:

a. providing experimental base values for a base at a position in a statistically significant set of target nucleic acids;

b. creating a distribution of said experimental base values;

c. determining a relative base probability of a base at a position of a target nucleic acid by comparing its experimental base value with the distribution of experimental base values.

2. The method of claim 1, wherein the experimental base values are obtained for the same position in a target nucleic acid relative to a priming site or adaptor binding site.

3. The method of claim 1, wherein the method further comprises an adjustment of the experimental base values before creation of said distribution.

4. The method of claim 3, wherein the adjustment is a normalization of experimental base values.

5. The method of claim 1, wherein all experimental base values are obtained in a single sequencing experiment.

12. The method of claim 1, wherein the method further comprises:

(d) calling a base at a specific position in the target nucleic acid based on its relative base probability.

6. The method of clam 1, wherein the base probability is determined using multiple experimental base values for one base for a position in the set of target nucleic acids.

7. The method of clam 1, wherein the base probability is determined using multiple experimental base values for all bases for a position in the set of target nucleic acid.

8. The method of clam 7, wherein the base probability is determined for each base for a position in a target nucleic acid.

9. The method of clam 7, wherein four groups of four experimental base value distributions are created.

10. The method of clam 8, wherein the distribution is characterized by clustering.

11. The method of clam 8, wherein the base probabilities are determined for multiple positions in a target nucleic acid.

13. A method for determining relative base probabilities, comprising:

a. providing experimental base values for a base at a position in set of target nucleic acids;

b. dividing said base values into two or more groups according to associated experimental measurements, wherein each group comprises a statistically significant number of experimental base values;

c. creating a distribution of said bases values for each group of step (b);

d. determining the relative base probability of a base in a position of a target nucleic in each group by comparing its experimental base value with the distribution of experimental base values in the relevant group.

14. The method of claim 13, wherein the associated experimental measurements comprise experimental base values for one or more other positions within said target nucleic acids.

15. The method of claim 13, wherein the associated experimental measurements comprise the quantity of target nucleic acid analyzed.

16. The method of claim 13, wherein the associated experimental measurements comprise the nucleotide base content of the target nucleic acid.

17. The method of claim 13, wherein the base probability is determined using multiple experimental base values for all bases for a position in the relevant group of target nucleic acids.

18. The method of claim 17, wherein the base probability is determined for each base for a position in a target nucleic acid.

19. The method of claim 13, wherein the distributions of said base values for each group of step (b) are provided by previous or control experiments;

20. The method of claim 13, wherein the method further comprises:

(e) calling a base at a specific position in the target nucleic acid based on its relative base probability.

21. A method of determining a relative base probability in a target nucleic acid, comprising the steps of:

a. obtaining a plurality of experimental intensity base values at a position in a target nucleic acid;

b. dividing the experimental intensity values into groups based on the identification of a second base in a target nucleic acid with a known position relative to the first base;

c. creating an intensity value distribution for each group based on the plurality of base values obtained, wherein the groups comprise statistically significant number of experimental intensity values; and

d. comparing the experimental intensity value of the first base to the distribution created from a relevant group to determine a relative base probability.

22. A computer program for determining relative base probabilities, comprising:

a. computer code that receives a plurality of signals corresponding to base values for a target nucleic acid;

b. computer code for creating a distribution of said experimental base values;

c. computer code for determining a relative base probability of a base at a position of the target nucleic acid by comparing its experimental base value with the distribution of experimental base values; and

d. a computer readable medium that stores said computer codes.

23. The program of claim 22, further comprising:

a. computer code that generates a base call for the base at a position in a target nucleic acid.

24. A system for determining relative base probabilities, comprising:

a. a processor; and

b. a computer readable medium coupled to said processor for storing a computer program comprising;

i. computer code that receives a plurality of signals corresponding to a statistically significant number of experimental base values for a target nucleic acid;

ii. computer code for creating a distribution of said experimental base values; and

iii. computer code for determining a relative base probability of a base at a position of the target nucleic acid by comparing its experimental base value with the distribution of experimental base values.

25. The system of claim 24, further comprising:

iv. computer code that generates a base call for the base at a position in a target nucleic acid.