Methods and systems for evaluating CGH candidate probe nucleic acid sequences

• US 7,979,215 B2
• Filed: 07/30/2007
• Issued: 07/12/2011
• Est. Priority Date: 07/30/2007
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Sampas, Nicholas M.
• Primary Examiner(s): Zeman; Mary K
• Application Number:
  US11/888,038
• Publication Number:
  US 20090035764A1
• Time in Patent Office: 1,443 Days
• Field of Search: None
• US Class Current: 702/19
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/10 Ploidy or copy number detection
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/20 Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation

Abstract

Methods of evaluating candidate CGH probe nucleic acid sequences are provided. Aspects of the methods include providing a candidate CGH probe nucleic acid sequence for a target sequence of a copy number variation (CNV) of a genome. A proximity score is then determined for the candidate CGH probe nucleic acid sequence and employed to evaluate the sequence. Aspects of the invention further include computer programming and systems that include the same which are configured to evaluate candidate CGH probe nucleic acid sequences using a proximity score.

Claims

1. A method comprising:

(a) providing a candidate CGH probe nucleic acid sequence complementary to a target sequence of a copy number variation (CNV) in a genome;

(b) calculating a proximity score for said candidate CGH probe nucleic acid sequence, wherein said proximity score is determined by proximity to said target sequence of one or more sequences homologous to said target sequence;

wherein said proximity score is an indicator of suitability of said candidate CGH probe nucleic acid sequence for use in detecting said CNV,

wherein said method is implemented on a specifically programmed computer.

2. The method according to claim 1, wherein said proximity score is determined from an estimate (D) of signal contributions from hybridization of said candidate CGH probe nucleic acid sequence to said one or more sequences distal to said target sequence.

3. The method according to claim 2, wherein said proximity score is determined using the formula:

Proximity score=1/(1+D).

4. The method according to claim 1, wherein said proximity score is determined from an estimate (D) of signal contributions from hybridization of said candidate CGH probe nucleic acid sequence to said one or more sequences distal to said target sequence and also from an estimate (P) of signal contributions from hybridization of said candidate CGH probe to said one or more sequences at least proximal to said target sequence.

5. The method according to claim 4, wherein said hybridization of said candidate CGH probe nucleic acid sequence to said one or more sequences at least proximal to said target sequence comprises hybridization occurring at said target sequence and proximal to said target sequence.

6. The method according to claim 5, wherein said proximity score is determined using the formula:

Proximity score=P/(P+D).

7. The method according to claim 1, wherein said proximity score is determined using a proximity weighting function.

8. The method according to claim 7, wherein said proximity weighting function is a “

top-hat”

function.

9. The method according to claim 7, wherein said proximity weighting function is a continuous function.

10. The method according to claim 9, wherein said proximity weighting function is a Lorentzian function.

11. The method according to claim 1, wherein said outputting comprises recording said result to a physical medium.

12. The method according to claim 1, wherein at least two different candidate CGH probe nucleic acid sequences of differing sequence are provided in step (a), and step (b) is carried out on said at least two different candidate CGH probe nucleic acid sequences.

13. The method according to claim 1, wherein said method further comprises synthesizing a probe nucleic acid having a sequence of said candidate CGH probe nucleic acid sequence.

14. The method according to claim 13, wherein said method further comprises assaying said probe nucleic acid in a hybridization assay.

15. The method according to claim 1, wherein said method further comprises fabricating a nucleic acid array that comprises said candidate CGH probe nucleic acid sequence.

16. The method according to claim 15, wherein said method further comprises contacting said nucleic acid array with a genomic sample.

17. A computer readable storage medium carrying one or more sequences of instructions for evaluating a candidate probe CGH nucleic acid sequence, wherein execution of said one or more sequences of instructions by one or more processors causes the one or more processors to perform the step of:

calculating a proximity score for a candidate CGH probe nucleic acid sequence complementary to a target sequence of a copy number variation (CNV) in a genome, wherein said proximity score is determined by proximity to said target sequence of one or more sequences homologous to said target sequence;

wherein said proximity score is an indicator of suitability of said candidate CGH probe nucleic acid sequence for use in detecting said CNV.

18. A computer-based system for evaluating a candidate probe CGH nucleic acid sequence, said computer-based system comprising:

(a) a communication module comprising an input manager for receiving input from a user and an output manager for communicating output to a user;

(b) a processor comprising a candidate probe CGH nucleic acid sequence manager program that causes the processor to;

calculate a proximity score for a candidate CGH probe nucleic acid sequence complementary to a target sequence of a copy number variation (CNV) in a genome, wherein said proximity score is determined by proximity to said target sequence of one or more sequences homologous to said target sequence and wherein said proximity score is an indicator of suitability of said candidate CGH probe nucleic acid sequence for use in detecting said CNV.