Enhanced risk probabilities using biomolecule estimations

• US 8,756,020 B2
• Filed: 10/15/2011
• Issued: 06/17/2014
• Est. Priority Date: 01/25/2011
• Status: Active Grant

• Current Assignee: Roche Molecular Systems (Roche Holding AG)
• Original Assignee: Ariosa Diagnostics Incorporated (Roche Holding AG)
• Inventors: Struble, Craig, Wang, Eric, Sparks, Andrew, Oliphant, Arnold
• Primary Examiner(s): SIMS, JASON M
• Application Number:
  US13/274,309
• Publication Number:
  US 20120190018A1
• Time in Patent Office: 976 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

Abstract

The present invention provides processes for determining more accurate risk probabilities for medical conditions. The risk probabilities of the presence or absence of a medical condition are calculated using frequency data from selected biomolecules and biomolecule source contribution of at least one source in a mixed sample.

Claims

1. A computer-implemented process for calculating risk probabilities for fetal aneuploidies in a maternal sample, wherein at least one processor coupled to a memory executes a software component that performs the process comprising:

determining a frequency of a first set of at least twelve or more non-polymorphic loci from a first chromosome in the maternal sample;

determining a frequency of a second set of at least twelve or more non-polymorphic loci from a second chromosome in the maternal sample;

determining the frequency of a third set of at least twelve or more polymorphic loci from one or more chromosomes other than the first and second chromosome in the maternal sample;

determining an overall frequency of the non-polymorphic and polymorphic loci;

computing a chromosome proportion metric for the first and second chromosome in the maternal sample using the overall frequency of the non-polymorphic loci;

comparing the frequency of the polymorphic loci to determine a percent fetal nucleic acid in the maternal sample;

for each first and second chromosome, measuring a deviation from an expected chromosome proportion metric when a chromosome is euploid;

for each first and second chromosome, measuring a deviation from an expected chromosome proportion metric when a chromosome is aneuploid using the computed percent fetal nucleic acid in the maternal sample; and

calculating an initial risk probability score for the maternal sample based on the deviations from the expected chromosome proportion metrics for the first and second chromosomes.

2. The process of claim 1, wherein the maternal sample is maternal blood, maternal plasma or maternal serum.

3. The process of claim 1, wherein the maternal sample is maternal plasma.

4. The process of claim 1, wherein the frequencies of the non-polymorphic and polymorphic loci are determined by sequencing.

5. The process of claim 4, wherein the non-polymorphic and polymorphic loci are preselected through sequence-specific amplification of loci prior to sequencing.

6. The process of claim 4, wherein the frequencies of the non-polymorphic and polymorphic loci are determined through massively parallel shotgun sequencing.

7. The process of claim 1, wherein the frequencies of the non-polymorphic and polymorphic loci are determined using digital PCR.

8. The process of claim 1, further comprising adjusting the calculated initial risk probability using ancillary information.

9. The process of claim 8, wherein the ancillary information is maternal age.

10. The process of claim 8, wherein the ancillary information is gestational age.

11. The process of claim 8, wherein the ancillary information is results from a prior medical test or procedure.