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US 2021/0174894 A1Published application
Methods and processes for non-invasive assessment of genetic variations
AssigneeSequenom, Inc.
InventorsZeljko DZAKULA, Cosmin DECIU, Chen ZHAO
Life of this patent
Estimating the term…
Abstract
A method and system for analyzing circulating cell-free nucleic acids from a pregnant female with reduced bias. Counts of sequence reads mapped to portions of a reference genome are obtained. A regression model is generated that models the relationship between the counts and the GC content. The read counts are normalized according to the regression model to remove the GC bias. The normalized counts are used for further analysis, such as the detection of fetal aneuploidy.
Claims21
(canceled)
A method for calculating with reduced bias genomic section levels for a test sample, comprising:
- (a) obtaining counts of sequence reads mapped to portions of a reference genome, which sequence reads are reads of circulating cell-free nucleic acid from a test sample;
- (b) determining one or more estimates of curvature for the test sample from a fitted relation between (i) the counts of the sequence reads mapped to the portions of the reference genome, and (ii) a mapping feature for each of the portions of the reference genome;
- and
- (c) calculating a normalized genomic section level of each of the portions of the reference genome for the test sample according to
- (1) counts of the sequence reads mapped to each of the portions of the reference genome for the test sample,
- (2) the one or more estimates of curvature determined in (b) for the test sample, and
- (3) one or more portion-specific estimates of curvature of each of multiple portions of the reference genome from a fitted relation between (i) one or more sample-specific estimates of curvature for a plurality of samples, and (ii) the counts of the sequence reads mapped to each of the portions of the reference genome for the plurality of samples,
- thereby providing calculated genomic section levels,
- whereby bias in the counts of the sequence reads mapped to each of the portions of the reference genome is reduced in the calculated genomic section levels.
6 more elements
A system comprising one or more computers and memory,
- which memory comprises instructions executable by the one or more computers and which memory comprises counts of sequence reads mapped to portions of a reference genome, which sequence reads are reads of circulating cell-free nucleic acid from a test sample;
- and
- which instructions executable by the one or more computers are configured to:
- (a) determine one or more estimates of curvature for the test sample from a fitted relation between (i) the counts of the sequence reads mapped to the portions of the reference genome, and (ii) a mapping feature for the portions of the reference genome;
- and
- (b) calculate a normalized genomic section level of each of the portions of the reference genome for the test sample according to
- (1) counts of the sequence reads mapped to each of the portions of the reference genome for the test sample,
- (2) the one or more estimates of curvature determined in (b) for the test sample, and
- (3) one or more portion-specific estimates of curvature of each of multiple portions of the reference genome from a fitted relation between (i) one or more sample-specific estimates of curvature for a plurality of samples, and (ii) the counts of the sequence reads mapped to each of the portions of the reference genome for the plurality of samples,
- thereby configured to provide calculated genomic section levels,
- whereby bias in the counts of the sequence reads mapped to each of the portions of the reference genome is reduced in the calculated genomic section levels.
8 more elements
A non-transitory computer-readable storage medium with an executable program stored thereon, wherein the program instructs a computer to perform the following:
- (a) access nucleotide sequence reads mapped to portions of a reference genome, which sequence reads are reads of circulating cell-free nucleic acid from a test sample;
- (b) determine one or more estimates of curvature for the test sample from a fitted relation between (i) the counts of the sequence reads mapped to the portions of the reference genome, and (ii) a mapping feature for the portions of the reference genome;
- and
- (c) calculate a normalized genomic section level of each of the portions of the reference genome for the test sample according to
- (1) counts of the sequence reads mapped to each of the portions of the reference genome for the test sample,
- (2) the one or more estimates of curvature determined in (b) for the test sample, and
- (3) one or more portion-specific estimates of curvature of each of multiple portions of the reference genome from a fitted relation between (i) one or more sample-specific estimates of curvature for a plurality of samples, and (ii) the counts of the sequence reads mapped to each of the portions of the reference genome for the plurality of samples,
- thereby configured to provide calculated genomic section levels,
- whereby bias in the counts of the sequence reads mapped to each of the portions of the reference genome is reduced in the calculated genomic section levels.
6 more elements
Dependencies are inferred from the claim text.