Methods and systems for analyzing nucleic acid sequences
AssigneeGrail, LLC
InventorSrinka GHOSH
Life of this patent
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Abstract
Methods of identifying changes in genomic DNA copy number are disclosed. This disclosure provides methods for detecting chromosomal aberrations in a subject using Hidden Markov modeling. In some cases, methods provided herein use de novo sequence assembly to detect chromosomal aberrations in a subject. The methods can be used to detect copy number changes in cancerous tissue compared to normal tissue. The methods can be used to diagnose cancer and other diseases associated with chromosomal anomalies.
Claims29
A method of analyzing nucleic acid molecules from a biological sample of a subject of an organism, the method comprising:
- (a) obtaining, in a computer system, sequence reads of the nucleic acid molecules from the biological sample of the subject;
- (b) identifying, in the computer system, a first genomic region in a reference genome of the organism with a mappability score below a threshold and a second genomic region in the reference genome of the subject with a mappability score above the threshold, wherein the second genomic region is adjacent to one end of the first genomic region;
- (c) performing, in the computer system, local de novo assembly of a first subset of the sequence reads that align to the first genomic region and a second subset of the sequence reads that align to the second genomic region, thereby generating contigs, wherein at least one of the contigs extends over a portion of the first genomic region and a portion of the second genomic region;
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- (d) recovering, in the computer system, sequence data corresponding to the contigs within the first genomic region, wherein the recovered genomic sequence data comprise at least a portion of the first subset of sequence read.
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A non-transitory computer-readable medium comprising machine executable code that, upon execution by one or more computer processors, implements a method of analyzing nucleic acid molecules from a biological sample of a subject of an organism, said method comprising:
- (a) obtaining sequence reads of the nucleic acid molecules from the biological sample of the subject;
- (b) identifying a first genomic region in a reference genome of the organism with a mappability score below a threshold and a second genomic region in the reference genome of the subject with a mappability score above the threshold, wherein the second genomic region is adjacent to one end of the first genomic region;
- (c) performing local de novo assembly of a first subset of the sequence reads that align to the first genomic region and a second subset of the sequence reads that align to the second genomic region, thereby generating contigs, wherein at least one of the contigs extends over a portion of the first genomic region and a portion of the second genomic region;
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- (d) recovering sequence data corresponding to the contigs within the first genomic region, wherein the recovered genomic sequence data comprise at least a portion of the first subset of sequence read.
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A system for analyzing nucleic acid molecules from a biological sample of a subject of an organism, comprising:
- a database that stores a plurality of sequence reads generated upon sequencing said nucleic acid molecules;
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- one or more computer processors operatively coupled to said database, wherein said one or more computer processors are individually or collectively programmed to execute general instructions for:
- (a) identifying a first genomic region in a reference genome of the organism with a mappability score below a threshold and a second genomic region in the reference genome of the subject with a mappability score above the threshold, wherein the second genomic region is adjacent to one end of the first genomic region;
- (b) performing local de novo assembly of a first subset of the sequence reads that align to the first genomic region and a second subset of the sequence reads that align to the second genomic region, thereby generating contigs, wherein at least one of the contigs extends over a portion of the first genomic region and a portion of the second genomic region;
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- (c) recovering sequence data corresponding to the contigs within the first genomic region, wherein the recovered genomic sequence data comprise at least a portion of the first subset of sequence read.
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Dependencies are inferred from the claim text.