Automated analysis of multiplexed probe-target interaction patterns: pattern matching and allele identification

• US 9,147,037 B2
• Filed: 11/16/2011
• Issued: 09/29/2015
• Est. Priority Date: 08/02/2004
• Status: Active Grant

• Current Assignee: BioArray Solutions Limited (Werfen SA)
• Original Assignee: BioArray Solutions Limited (Werfen SA)
• Inventors: Xia, Xiongwu, Seul, Michael
• Primary Examiner(s): Brusca, John S
• Application Number:
  US13/297,487
• Publication Number:
  US 20120065099A1
• Time in Patent Office: 1,413 Days
• US Class Current: 1/1
• CPC Class Codes: C12Q 1/6827 for detection of mutation or polymorphism
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 20/40 Population genetics; Linkage disequilibrium
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids

Abstract

Methods and algorithms for automated allele assignments within an integrated software environment are provided. These methods and algorithms offer a multiplicity of functionalities including: data management; system configuration including user authorization, training set analysis and probe masking; pattern analysis including string matching and probe flipping; and interactive redaction of data. The methods and algorithms further include methods of setting thresholds, refining thresholds, and probe masking of signals produced by probes which do not contribute significantly to discriminating among alleles.

Claims

1. A method comprising:

(i) providing a set of primers that generate targets from genomic regions which include a polymorphic locus of interest;

(ii) providing an expanded probe set comprising a core subset of probes that hybridize only to particular targets with particular alleles and a second subset of probes that hybridize to multiple targets;

(iii) exposing the targets to the expanded probe set under reaction conditions such that hybridization of targets and probes generates a signal;

(iv) masking the signal of hybridization of targets and members of the second subset of probes; and

(v) performing initial allele group assignments based only on the signal of hybridization of targets and members of the core subset of probes

(vi) performing, after step (v), allele group assignments based on the signal of hybridization of targets and the second subset of probes.

2. The method of claim 1, further comprising making final allele assignments where allele group assignments made based on the second probe set agree with allele group assignments made based on the first subset of probes.