Methods and processes for non-invasive assessment of genetic variations
First Claim
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1. A method for determining presence or absence of a chromosome trisomy for a test sample, comprising:
- (a) obtaining counts of sequence reads mapped to portions of a reference genome, which sequence reads are of circulating cell-free nucleic acid from a test sample from a pregnant female;
(b) determining a guanine and cytosine (GC) bias coefficient for the test sample based on a fitted relation between (i) the counts of the sequence reads mapped to each of the portions and (ii) GC content for each of the portions;
wherein the GC bias coefficient is a slope for a linear fitted relation;
(c) determining a genomic section level for each of the portions based on the counts of (a), the GC bias coefficient of (b) and a fitted relation, for each of the portions, between (i) the GC bias coefficient for each of multiple samples and (ii) the counts of the sequence reads mapped to each of the portions for the multiple samples, thereby providing calculated genomic section levels; and
(d) determining presence or absence of a chromosome trisomy for the test sample according to the calculated genomic section levels.
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Abstract
Provided herein are methods, processes and apparatuses for non-invasive assessment of genetic variations.
158 Citations
33 Claims
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1. A method for determining presence or absence of a chromosome trisomy for a test sample, comprising:
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(a) obtaining counts of sequence reads mapped to portions of a reference genome, which sequence reads are of circulating cell-free nucleic acid from a test sample from a pregnant female; (b) determining a guanine and cytosine (GC) bias coefficient for the test sample based on a fitted relation between (i) the counts of the sequence reads mapped to each of the portions and (ii) GC content for each of the portions;
wherein the GC bias coefficient is a slope for a linear fitted relation;(c) determining a genomic section level for each of the portions based on the counts of (a), the GC bias coefficient of (b) and a fitted relation, for each of the portions, between (i) the GC bias coefficient for each of multiple samples and (ii) the counts of the sequence reads mapped to each of the portions for the multiple samples, thereby providing calculated genomic section levels; and (d) determining presence or absence of a chromosome trisomy for the test sample according to the calculated genomic section levels. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
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17. A method for determining presence or absence of a chromosome trisomy for a test sample, comprising:
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(a) obtaining counts of sequence reads mapped to portions of a reference genome;
which sequence reads are of circulating cell-free nucleic acid from a test sample from a pregnant female;(b) (i) normalizing the counts in (a), thereby generating normalized counts, and removing normalized counts associated with one or more filtered portions, thereby yielding filtered normalized counts;
or (b) (ii) removing counts associated with one or more filtered portions, and normalizing the counts in portions that were not removed, thereby yielding filtered normalized counts;
wherein;(1) the one or more filtered portions were selected according to one or more criteria chosen from measure of error or mappability, or measure of error and mappability; and (2) the normalizing comprises; determining a guanine and cytosine (GC) bias coefficient for the test sample based on a fitted relation between (i) the counts of the sequence reads mapped to each of the portions and (ii) GC content for each of the portions, wherein the GC bias coefficient is a slope for a linear fitted relation; determining a genomic section level for each of the portions based on the counts of (a), the GC bias coefficient and a fitted relation, for each of the portions, between (i) the GC bias coefficient for each of multiple samples and (ii) the counts of the sequence reads mapped to each of the portions for the multiple samples, thereby providing calculated genomic section levels; and (c) determining presence or absence of a chromosome trisomy for the test sample according to the calculated genomic section levels. - View Dependent Claims (18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33)
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Specification