Methods and processes for non-invasive assessment of genetic variations
First Claim
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1. A computer-implemented method for determining fetal fraction based on a copy number variation in a maternal genome, comprising:
- (a) sequencing a test sample from a pregnant female bearing a fetus by a non-targeted massively parallel sequencing process that generates nucleotide sequence reads, the test sample comprising circulating cell-free nucleic acid from (i) a maternal genome and (ii) a fetal genome;
mapping the sequence reads to genomic sections of a reference genome; and
counting the sequence reads mapped to the genomic sections of the reference genome, thereby obtaining counts of sequence reads mapped to the genomic sections of the reference genome;
(b) normalizing, using a microprocessor, the counts mapped to the genomic sections of the reference genome, thereby providing normalized counts for the genomic sections;
(c) identifying a first elevation of the normalized counts for a first set of genomic sections significantly different than a second elevation of the normalized counts for a second set of genomic sections, wherein the first set of genomic sections and the second set of genomic sections are within the same chromosome;
(d) determining a copy number variation in the maternal genome for the first set of genomic sections based on the identified first and second elevations;
(e) determining a categorization for the copy number variation in the maternal genome by comparing the first elevation to expected elevations for predetermined copy number variation categorizations; and
(f) determining, using a microprocessor, a fetal fraction of the circulating cell-free nucleic acid according to the first elevation and a deviation from an expected elevation of normalized counts for the categorization.
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Abstract
Provided herein are methods, processes and apparatuses for non-invasive assessment of genetic variations.
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Citations
24 Claims
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1. A computer-implemented method for determining fetal fraction based on a copy number variation in a maternal genome, comprising:
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(a) sequencing a test sample from a pregnant female bearing a fetus by a non-targeted massively parallel sequencing process that generates nucleotide sequence reads, the test sample comprising circulating cell-free nucleic acid from (i) a maternal genome and (ii) a fetal genome;
mapping the sequence reads to genomic sections of a reference genome; and
counting the sequence reads mapped to the genomic sections of the reference genome, thereby obtaining counts of sequence reads mapped to the genomic sections of the reference genome;(b) normalizing, using a microprocessor, the counts mapped to the genomic sections of the reference genome, thereby providing normalized counts for the genomic sections; (c) identifying a first elevation of the normalized counts for a first set of genomic sections significantly different than a second elevation of the normalized counts for a second set of genomic sections, wherein the first set of genomic sections and the second set of genomic sections are within the same chromosome; (d) determining a copy number variation in the maternal genome for the first set of genomic sections based on the identified first and second elevations; (e) determining a categorization for the copy number variation in the maternal genome by comparing the first elevation to expected elevations for predetermined copy number variation categorizations; and (f) determining, using a microprocessor, a fetal fraction of the circulating cell-free nucleic acid according to the first elevation and a deviation from an expected elevation of normalized counts for the categorization. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
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Specification