System and method for identification of individual samples from a multiplex mixture

• US 20100267043A1
• Filed: 05/05/2010
• Published: 10/21/2010
• Est. Priority Date: 06/01/2007
• Status: Abandoned Application

• Current Assignee: 454 Life Sciences Corporation (Roche Holding AG)
• Original Assignee: 454 Life Sciences Corporation (Roche Holding AG)
• Inventors: Srinivasan, Maithreyan, Turenchalk, Gregory S., Simons, Jan Fredrik, Braverman, Michael S.
• Application Number:
  US12/800,043
• Publication Number:
  US 20100267043A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/68 involving nucleic acids

Abstract

An embodiment of an identifier element for identifying an origin of a template nucleic acid molecule is described that comprises a nucleic acid element comprising a sequence composition that enables detection of an introduced error in sequence data generated from the nucleic acid element and correction of the introduced error, where the nucleic acid element is constructed to couple with the end of a template nucleic acid molecule and identifies an origin of the template nucleic acid molecule.

Claims

1. to 14. (canceled)

15. A method for identifying an origin of a template nucleic acid molecule, comprising the steps of:

identifying a first identifier sequence from sequence data generated from a template nucleic acid molecule;

detecting an introduced error in the first identifier sequence;

correcting the introduced error in the first identifier sequence;

associating the corrected first identifier sequence with a first identifier element coupled to the template molecule; and

identifying an origin of the template molecule using the association of the corrected first identifier sequence with the first identifier element.

16. The method of claim 15, further comprising:

sequencing a template nucleic acid molecule to generate the sequence data.

17. The method of claim 15, wherein:

the template nucleic acid molecule is included in a multiplex sample comprising a plurality of template molecules from a plurality of different origins.

18. The method of claim 15, further comprising:

detecting up to three of the introduced errors in the first identifier sequence; and

correcting up to two of the introduced errors in the first identifier sequence.

19. The method of claim 15, wherein:

the introduced error is selected from the group consisting of an insertion error, a deletion error, and a substitution error.

20. The method of claim 15, wherein the step of detecting comprises:

measuring one or more characteristics of sequence composition in one or more sequence regions that flank the identifier sequence; and

detecting the introduced error using one or more assumptions derived from the measured characteristics.

21. The method of claim 15, wherein:

the first identifier element is incorporated into an adaptor comprising a primer element, wherein the adaptor is coupled to the template nucleic acid molecule.

22. The method of claim 21, wherein:

the first identifier element is in a known position relative to the primer element.

23. The method of claim 21, wherein:

the primer element is selected from the group consisting of an amplification primer, a sequencing primer, or a bipartite amplification—

sequencing primer.

24. The method of claim 21, wherein:

the adaptor comprises a quality control element.

25. The method of claim 21, wherein:

the first identifier element is in a known position relative to the quality control element.

26. The method of claim 15, wherein:

the origin of the template nucleic acid molecule comprises an experimental sample or diagnostic sample.

27. The method of claim 15, further comprising the steps of:

identifying a second identifier sequence from the sequence data generated from the template nucleic acid molecule;

detecting an introduced error in the second identifier sequence;

correcting the introduced error in the second identifier sequence;

associating the corrected second identifier sequence with a second identifier element coupled with the template nucleic acid molecule; and

identifying an origin of the template nucleic acid molecule using the association of the corrected second identifier sequence with the second identifier element combinatorially with the association of the corrected first identifier sequence with the first identifier element.

28. The method of claim 27, further comprising:

detecting up to three of the introduced errors in the second identifier sequence; and

correcting up to two of the introduced errors in the second identifier sequence.

29. The method of claim 15, wherein:

the introduced error is selected from the group consisting of an insertion error, a deletion error, and a substitution error.

30. The method of claim 15, wherein:

the first identifier belongs to at least one set of compatible identifiers of a plurality of sets of identifiers.

31. The method of claim 15, wherein:

the set of compatible identifiers comprise 14 identifiers that enable the detection and the correction of the introduced error.

32. to 41. (canceled)

42. A computer, comprising executable code stored thereon, wherein the executable code performs a method for identifying an origin of a template nucleic acid molecule, comprising the steps of:

identifying an identifier sequence from sequence data generated from a template nucleic acid molecule;

detecting an introduced error in the identifier sequence;

correcting the introduced error in the identifier sequence;

associating the corrected identifier sequence with an identifier element coupled with the template molecule; and

identifying an origin of the template molecule using the association of the corrected identifier sequence with the identifier element.

43. The method of claim 42, wherein:

the template nucleic acid molecule is included in a multiplex sample comprising a plurality of template molecules from a plurality of different origins.

44. The method of claim 42, further comprising:

detecting up to three of the introduced errors in the first identifier sequence; and

correcting up to two of the introduced errors in the first identifier sequence.

45. The method of claim 42, wherein:

the introduced error is selected from the group consisting of an insertion error, a deletion error, and a substitution error.

46. The method of claim 42, wherein the step of identifying further comprises:

determining a position for the identifier sequence using a known positional relationship of one or more elements in the sequence data.

47. The method of claim 46, wherein:

the one or more elements include a primer sequence.

48. The method of claim 42, wherein the step of detecting further comprises:

measuring one or more characteristics of sequence composition in one or more sequence regions that flank the identifier sequence; and

detecting the introduced error using one or more assumptions derived from the measured characteristics.

49. The method of claim 42, further comprising:

identifying a second identifier sequence from the sequence data generated from the template nucleic acid molecule;

detecting an introduced error in the second identifier sequence;

correcting the introduced error in the second identifier sequence;

associating the corrected second identifier sequence with a second identifier element coupled with the template molecule; and

identifying an origin of the template molecule using the association of the corrected second identifier sequence with the second identifier element combinatorially with the association of the corrected first identifier sequence with the first identifier element.