Granted Patent B2

US 12,400,736 · App. 17/226,580 · Granted Aug 26, 2025

Inventors: Lin Tang (San Diego, CA); Cosmin Deciu (San Diego, CA)

Assignee: SEQUENOM, INC.

G16B20/20C12Q1/6869C12Q1/6874G16B20/00G16B30/10G16B40/20G16B40/30G16B20/10G16B30/00G16B40/00

Abstract

Claims (17)

1. A method for non-invasive estimation of fetal fraction comprising:

(a) sequencing circulating cell-free nucleic acid from a test sample from a pregnant subject by a massively parallel sequencing (MPS) process, thereby generating a subject data set comprising nucleic acid sequence reads;

(b) receiving a reference data set comprising nucleic acid sequence reads from multiple female reference samples;

(c) generating a linear relation of a log sequence read count ratio and GC content for the subject data set;

(d) performing a linear modeling analysis in pairwise analyses between respective pairs in the subject data set and the reference data set; and

(e) estimating fetal fraction for the test sample based on an average fetal fraction determined according to a deviation of chromosome X from an expected position to an observed position in each pairwise analysis.

2. The method of claim 1 , wherein the subject data set comprises millions of nucleic acid sequence reads.

3. The method of claim 1 , wherein the reference data set comprises millions of nucleic acid sequence reads.

4. The method of claim 1 , wherein (c), (d), and (e) are performed by a processor.

5. The method of claim 1 , wherein the test sample is from the pregnant subject and some or all of the reference samples are from different persons.

6. The method of claim 1 , further comprising mapping the nucleic acid sequence reads to portions of a reference genome.

7. The method of claim 1 , further comprising, prior to the sequencing, isolating the circulating cell-free nucleic acid from the test sample from the pregnant subject.

8. The method of claim 1 , wherein the circulating cell-free nucleic acid is from blood, serum, or blood plasma from the pregnant subject.

9. The method of claim 1 , wherein the massively parallel sequencing (MPS) process is performed at a coverage of about 1-fold or less.

10. The method of claim 1 , wherein the massively parallel sequencing (MPS) process is performed at a coverage of about 0.2-fold to about 1-fold.

11. The method of claim 1 , wherein (d) comprises generating a z-score based on the linear modeling analysis for the pairwise samples.

12. The method of claim 1 , further comprising sequencing circulating cell-free nucleic acid from multiple female reference samples by a massively parallel sequencing (MPS) process, thereby generating the reference data set comprising nucleic acid sequence reads from the multiple female reference samples.

Assignments (1)

Continuity (4)

References Cited (400)