NON-INVASIVE DETERMINATION OF METHYLOME OF FETUS OR TUMOR FROM PLASMA
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Abstract
Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.
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Citations
43 Claims
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1. (canceled)
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2. A method of determining a type of cancer by analyzing cell-free DNA molecules from a biological sample of an organism, the method comprising:
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(a) obtaining sequence reads from cell-free DNA molecules from a biological sample, wherein the sequence reads comprise a methylation status of the cell-free DNA molecules; (b) analyzing the sequence reads to determine, at single nucleotide resolution, methylation statuses for a plurality of sites in the cell-free DNA molecules; (c) determining a methylation profile from the methylation statuses for the plurality of sites; and (d) determining a type of cancer based at least in part on the methylation profile. - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)
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35. A non-transitory computer-readable medium comprising a series of instructions that, upon execution by one or more computer processors of a computer system, causes the computer system to perform:
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(a) obtaining sequence reads from cell-free DNA molecules from a biological sample, wherein the sequence reads comprise a methylation status of the cell-free DNA molecules; (b) processing the sequence reads to determine methylation statuses for a plurality of sites, at single nucleotide resolution, in the cell-free DNA molecules; (c) determining a methylation profile from the methylation statuses of the plurality of sites; and (d) determining a type of cancer based at least in part on the methylation profile.
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36. A method of analyzing a biological sample from a subject, the method comprising:
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(a) obtaining sequence reads for cell-free DNA molecules from a biological sample of a subject, wherein the sequence reads include methylation statuses for the cell-free DNA molecules at single nucleotide resolution; (b) analyzing the sequence reads to determine a methylation profile for a plurality of sites based on the methylation statuses for the plurality of sites; and (c) determining a tissue source for at least a portion of the cell-free DNA molecules from the biological sample based, at least in part, on the methylation profile. - View Dependent Claims (37, 38, 39, 40, 41, 42)
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43. A non-transitory computer-readable medium comprising instructions that, upon execution by one or more computer processors of a computer system, causes the computer system to perform a method, the method comprising:
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(a) obtaining sequence reads for cell-free DNA molecules from a biological sample of a subject, wherein the sequence reads include methylation statuses for the cell-free DNA molecules at single nucleotide resolution; (b) analyzing the sequence reads to determine a methylation profile for a plurality of sites based on methylation statuses of the plurality of sites; and (c) determining a tissue source for at least a portion of the cell-free DNA molecules from the biological sample based, at least in part, on the methylation profile.
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Specification