Methods and processes for non-invasive assessment of genetic variations
First Claim
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1. A computer-implemented method for determining the presence or absence of a microduplication or microdeletion in a fetus, comprising:
- (a) receiving input information comprising nucleic acid sequence reads obtained by non-targeted multiplexed massively parallel sequencing of circulating cell-free nucleic acid from a test sample from a pregnant female bearing a fetus, and mapping the nucleic acid sequence reads to portions of a reference genome;
(b) normalizing, using a microprocessor, counts of the nucleic acid sequence reads mapped to portions of the reference genome, wherein the normalizing comprises normalization of guanine and cytosine (GC) bias and an adjustment according to a principal component analysis, thereby providing normalized counts;
(c) segmenting, using a microprocessor, the normalized counts of the portions or the normalized counts in a subset of the portions, thereby providing one or more discrete segments;
(d) identifying, using a microprocessor, a candidate segment among the one or more discrete segments, wherein the candidate segment is identified according to an area under a curve (AUC) analysis, wherein;
i) the AUC analysis is based on a number of portions covered by the segment and an absolute value of a level of normalized counts for the segment, wherein the level corresponds to a negative value of normalized counts for a deletion or a positive value of normalized counts for a duplication; and
ii) the candidate segment has the largest AUC of all the segments on the same chromosome; and
(e) determining the presence or absence of the microduplication or microdeletion according to the candidate segment.
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Abstract
Provided herein are methods, processes and apparatuses for non-invasive assessment of genetic variations that make use of decision analyses. The decision analyses sometimes include segmentation analyses and/or odds ratio analyses.
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Citations
20 Claims
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1. A computer-implemented method for determining the presence or absence of a microduplication or microdeletion in a fetus, comprising:
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(a) receiving input information comprising nucleic acid sequence reads obtained by non-targeted multiplexed massively parallel sequencing of circulating cell-free nucleic acid from a test sample from a pregnant female bearing a fetus, and mapping the nucleic acid sequence reads to portions of a reference genome; (b) normalizing, using a microprocessor, counts of the nucleic acid sequence reads mapped to portions of the reference genome, wherein the normalizing comprises normalization of guanine and cytosine (GC) bias and an adjustment according to a principal component analysis, thereby providing normalized counts; (c) segmenting, using a microprocessor, the normalized counts of the portions or the normalized counts in a subset of the portions, thereby providing one or more discrete segments; (d) identifying, using a microprocessor, a candidate segment among the one or more discrete segments, wherein the candidate segment is identified according to an area under a curve (AUC) analysis, wherein; i) the AUC analysis is based on a number of portions covered by the segment and an absolute value of a level of normalized counts for the segment, wherein the level corresponds to a negative value of normalized counts for a deletion or a positive value of normalized counts for a duplication; and ii) the candidate segment has the largest AUC of all the segments on the same chromosome; and (e) determining the presence or absence of the microduplication or microdeletion according to the candidate segment. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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Specification