Oligomer sequences mapping

• US 8,615,365 B2
• Filed: 02/02/2010
• Issued: 12/24/2013
• 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
• Primary Examiner(s): Skibinsky, Anna
• Application Number:
  US12/698,965
• Publication Number:
  US 20100286925A1
• Time in Patent Office: 1,421 Days
• Field of Search: None
• 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, the method comprising:

receiving a data set including two or more related oligomer sequences obtained from a fragment of genetic material;

receiving a key pattern corresponding to a reference index that was generated by applying the key pattern to a reference;

assuming a first separation distance between two of the related oligomer sequences to create a first possible sequence;

applying the key pattern to the first possible sequence to generate a first key, the key pattern selecting which bases of the first possible sequence are to be used in generating the first key;

assuming a second separation distance between the two related oligomer sequences to create a second possible sequence, the second separation distance being different than the first separation distance;

applying the key pattern to the second possible sequence to generate a second key, the second key including different bases than the first key; and

comparing the first and second generated keys to the reference index to determine candidate locations of the two oligomer sequences in the reference, wherein the method is performed with a computer.

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 first 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 the steps are performed for two or more data sets of related oligomer sequences.

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

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

7. The method of claim 6, wherein the reference comprises a human genomic sequence.

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

9. The method of claim 8, wherein the RNA or cDNA sequence comprises a human sequence.

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

11. The method of claim 1, wherein a statistical probability of relationships of the related oligomer sequences is utilized to evaluate candidate locations of the oligomer sequences in the reference.

12. 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.

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

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

15. 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.

16. The method of claim 1, wherein different separation distances between the two related oligomer sequences provide different keys that are consistent with the data set of related oligomer sequences.

17. The method of claim 1, wherein the first separation distance is a negative distance.

18. The method of claim 16, further comprising:

determining that the negative distance is consistent with the two related oligomer sequences.

19. The method of claim 1, further comprising:

receiving a second key pattern corresponding to a second reference index that was generated by applying the second key pattern to the reference;

assuming a third separation distance between the two related oligomer sequences to create a third possible sequence;

applying the second key pattern to the third possible sequence to generate a third key, the second key pattern selecting which bases of the third possible sequence are to be used in generating the third key;

assuming a fourth separation distance between the two related oligomer sequences to create a fourth possible sequence, the fourth separation distance being different than the third separation distance;

applying the second key pattern to the fourth possible sequence to generate a fourth key, the fourth key including different bases than the third key; and

comparing the third and fourth generated keys to the second reference index to determine candidate locations of the two oligomer sequences in the reference.

20. The method of claim 1, further comprising:

receiving a second key pattern corresponding to a second reference index that was generated by applying the second key pattern to the reference;

assuming a third separation distance between a different pair of the related oligomer sequences to create a third possible sequence;

applying the second key pattern to the third possible sequence to generate a third key, the second key pattern selecting which bases of the third possible sequence are to be used in generating the third key;

assuming a fourth separation distance between the different pair of the related oligomer sequences to create a fourth possible sequence, the fourth separation distance being different than the third separation distance;

applying the second key pattern to the fourth possible sequence to generate a fourth key, the fourth key including different bases than the third key; and

comparing the third and fourth generated keys to the second reference index to determine candidate locations of the different pair of the oligomer sequences in the reference.

21. An oligomer sequence mapping system, comprising:

an interface configured to;

receive a data set including two or more related oligomer sequences obtained from a fragment of genetic material; and

a processor coupled to the interface, configured to;

receive a key pattern corresponding to a reference index that was generated by applying the key pattern to a reference;

assume a first separation distance between two of the related oligomer sequences to create a first possible sequence;

apply the key pattern to the first possible sequence to generate a first key, the key pattern selecting which bases of the first possible sequence are to be used in generating the first key;

assume a second separation distance between the two related oligomer sequences to create a second possible sequence, the second separation distance being different than the first separation distance;

apply the key pattern to the second possible sequence to generate a second key, the second key including different bases than the first key; and

compare the first and second generated keys to the reference index to determine candidate locations of the two oligomer sequences in the reference.

22. The system of claim 21, wherein the processor is further configured to validate candidate locations by comparing all bases of the dataset to indicated portions of the reference.

23. The system of claim 21, wherein the processor is further configured to output locations of the related oligomer sequences in the reference.

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

receiving a data set including two or more related oligomer sequences obtained from a fragment of genetic material;

receiving a key pattern corresponding to a reference index that was generated by applying the key pattern to a reference;

assuming a first separation distance between two of the related oligomer sequences to create a first possible sequence;

applying the key pattern to the first possible sequence to generate a first key, the key pattern selecting which bases of the first possible sequence are to be used in generating the first key;

assuming a second separation distance between the two related oligomer sequences to create a second possible sequence, the second separation distance being different than the first separation distance;

applying the key pattern to the second possible sequence to generate a second key, the second key including different bases than the first key; and

comparing the first and second generated keys to the reference index to determine candidate locations of the two oligomer sequences in the reference.

25. The product of claim 24, further comprising computer instructions for validating candidate locations by comparing all bases of the dataset to indicated portions of the reference.

26. The product of claim of 25, wherein the validated locations are further utilized in sample analysis.