OLIGOMER SEQUENCES MAPPING

• US 20100286925A1
• Filed: 02/02/2010
• Published: 11/11/2010
• Est. Priority Date: 02/03/2009
• Status: Active Grant

• Current Assignee: Complete Genomics Incorporated (BGI Genomics Co., Ltd.)
• Original Assignee: Complete Genomics Incorporated (BGI Genomics Co., Ltd.)
• Inventors: Halpern, Aaron L., Nazarenko, Igor
• Granted Patent: US 8,615,365 B2
• Time in Patent Office: Days
• US Class Current: 702/19
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: G16B 30/10 Sequence alignment; Homology search
• CPC Class Codes: G16B 30/20 Sequence assembly

Abstract

Mapping oligomer sequences includes receiving a set of related oligomer sequences, applying one or more key patterns derived from a set of oligomer sequence relationships to obtain one or more keys that are consistent with the set of related oligomer sequences, and locating the one or more keys in an index configured to map a plurality of possible keys to their respective candidate and/or validated locations in a reference.

Claims

1. A method of oligomer sequence mapping, comprising:

a. receiving a data set of related oligomer sequences;

b. applying one or more key patterns to the oligomer sequences in the data set to generate one or more keys; and

c. comparing the generated keys to a reference index to determine candidate locations of the oligomer sequences in the reference.

2. The method of claim 1, wherein the bases of the data set which are selected by the key pattern are reordered to form the key.

3. The method of claim 1, wherein the bases of the data set which are selected by the key pattern are in original order.

4. The method of claim 1, wherein a set of sequences representing possible oligomer relationships is derived from the data set, and wherein the key pattern is applied to this set of derived sequences.

5. The method of claim 4, wherein the data set is re-ordered.

6. The method of claim 4, wherein the data set or portions thereof are reverse-complemented.

7. The method of claim 1, wherein the steps are performed for two or more data sets of related oligomer sequences.

8. The method of claim 1, wherein two or more oligomer sequences of the data set have an unknown separation distance.

9. The method of claim 1, wherein two or more oligomer sequences of the data set have a known distance relationship.

10. The method of claim 1, wherein the reference comprises genomic sequence.

11. The method of claim 10, wherein the reference comprises human genomic sequence.

12. The method of claim 1, wherein the reference comprises RNA or cDNA sequence.

13. The method of claim 12, wherein the RNA or cDNA sequence comprises human sequence.

14. The method of claim 1, wherein the reference includes one or more variations of a sequence.

15. The method of claim 1, wherein the statistical probability of relationships of the related oligomers is utilized to evaluate candidate locations of the oligomer sequence in the reference.

16. The method of claim 1, further comprising verification of the candidate locations in the reference to provide one or more validated locations in the reference.

17. The method of claim 1, further comprising outputting one or more candidate locations in the reference that map to the one or more keys.

18. The method of claim 1, further comprising outputting one or more validated locations in the reference that map to the one or more keys.

19. The method of claim 1, wherein the data set comprises an oligomer having a different length from at least one other oligomer in the data set.

20. A method of oligomer sequence mapping, comprising:

a. receiving a data set of related oligomer sequences;

b. determining sequences derived from possible oligomer relationships;

c. applying one or more key patterns to the derived sequences to generate one or more keys; and

d. comparing the generated keys to a reference index to determine candidate locations of the oligomer sequences in the reference.

21. The method of claim 20, further comprising:

e. validating candidate locations by comparing candidate locations to the indicated portions of the reference.

22. A method of oligomer sequence mapping, comprising:

a. receiving a data set of related oligomer sequences;

b. applying one or more key patterns to the oligomer sequences in the data set to generate one or more initial keys;

c. substituting at least one position in the initial key to generate a substituted key from the initial key, wherein the substituted key is a possible match to a reference; and

d. comparing the substituted keys to a reference index to determine candidate locations of the oligomer sequences in the reference.

23. The method of claim 22, further comprising:

e. validating candidate locations by comparing all bases of a dataset to the indicated portions of the reference.

24. The method of claim 22, wherein the position substituted comprises an ambiguous base in the data set.

25. The method of claim 24, wherein the position is substituted to create four possible matches to the reference.

26. The method of claim 22, wherein Xⁿ bases are substituted in the initial key to create the substituted key, wherein n is the number of ambiguous positions in the initial key and X is the number of bases to be substituted at the positions.

28. The method of claim 22, wherein the data set is reordered.

27. The method of claim 27, wherein X is four.

29. A method of oligomer sequence mapping, comprising:

a. receiving a data set of related oligomer sequences, wherein said data set comprises at least one ambiguous position;

b. applying one or more key patterns to the oligomer sequences in the data set to generate one or more initial keys,

c. removing the ambiguous position from the initial keys; and

d. comparing the keys with the removed position to a reference index to determine candidate locations of the oligomer sequences in the reference.

30. The method of claim 29, further comprising outputting one or more validated locations in the reference that map to the one or more keys.

31. An oligomer sequence mapping system, comprising:

a. an interface configured to receive a data set of related oligomer sequences;

b. a processor coupled to the interface, configured to;

i. apply one or more key patterns to information in the data set to generate one or more keys; and

ii. compare the generated keys to a reference index to determine candidate locations of the oligomer sequences in the reference.

32. The system of claim 31, wherein the processor is further configured to validate candidate locations by comparing all bases of a dataset to the indicated portions of the reference.

33. The system of claim 31, wherein the processor is further configured to output locations of the related oligomer sequences in the reference.

34. A computer program product for oligomer sequence mapping, the computer program product being embodied in a computer readable medium and comprising computer instructions for:

a. receiving a data set of related oligomer sequences;

b. applying one or more key patterns to information in the data set to generate one or more keys; and

c. comparing the generated keys to a reference index to determine candidate locations of the oligomer sequences in the reference.

35. The product of claim 34, further comprising computer instructions for validating candidate locations by comparing all bases of a dataset to the indicated portions of the reference

36. The product of claim of 35, wherein the validated locations are further utilized in sample analysis.