Highly sensitive surveillance using detection of cell free dna
AssigneeThe Medical College of Wisconsin, Inc.
InventorsAoy Tomita Mitchell, Michael Mitchell
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Abstract
Provided herein are methods and computer-readable storage media related to cell-free DNA and uses thereof to determine risk of a condition, such as transplant rejection or cancer, in a subject.
Claims157
A method of assessing a risk in a subject, the method comprising:
- analyzing nucleic acids from cell-free DNA extracted from a biological sample obtained from the subject to identify a plurality of loci, the nucleic acids comprising first nucleic acids of the subject and second nucleic acids not native to the subject;
- determining an allele of each of the plurality of loci;
- selecting at least one informative locus from the plurality of loci based on the determining of the allele;
- calculating an estimated allele frequency of a first allele at the at least one informative locus using a statistical distribution;
- determining an amount of cell-free DNA not native to the subject in the cell-free DNA based on the estimated allele frequency;
- and
- determining a risk in the subject based on the determined amount of the cell-free DNA not native to the subject in the cell-free DNA.
A method of treatment of a subject, the method comprising:
- determining an amount of cell-free DNA not native to the subject in cell-free DNA extracted from a biological sample from the subject;
- determining a risk in the subject based on the determined amount of the cell-free DNA not native to the subject;
- and
- administering a therapy, or providing information about a therapy, to the subject based on the determined risk.
A method of assessing a risk of a systemic disease in a recipient of a transplant, the method comprising:
- quantifying the amount of cell-free DNA extracted from a biological sample obtained from the recipient of a transplant;
- and
- determining a risk of a systemic disease in the recipient of a transplant based on the determined amount of the cell-free DNA.
A method of treatment of a recipient of a transplant, the method comprising:
- quantifying the amount of cell-free DNA extracted from a biological sample obtained from the recipient of a transplant;
- determining a risk of a systemic disease in the recipient of a transplant based on the determined amount of the cell-free DNA;
- and
- administering a therapy, or providing information about a therapy, to the recipient of a transplant based on the determined risk.
A method of evaluating a subject, comprising:
- calculating a value for a Predictive Model of Formula 1, Formula 2 or Formula 3;
- and
- assessing the condition of the recipient of a transplant.
The method of 118, further comprising determining an amount of non-native cell-free DNA in a biological sample from the subject.
At least one computer-readable storage medium storing computer-executable instructions that, when executed by at least one processor, cause a computing device to perform a method comprising:
- determining an allele of each of a plurality of loci;
- selecting at least one informative locus from the plurality of loci based on the determining of the allele;
- calculating an estimated allele frequency of a first allele at the at least one informative locus using a statistical distribution;
- determining an amount of cell-free DNA not native to a subject in the cell-free DNA based on the estimated allele frequency;
- and
- determining a risk in the subject based on the determined amount of the cell-free DNA not native to the subject in the cell-free DNA.
At least one computer-readable storage medium storing computer-executable instructions that, when executed by at least one processor, cause a computing device to perform a method comprising:
- determining an amount of cell-free DNA not native to a subject in cell-free DNA extracted from a biological sample from the subject;
- and
- determining a risk in the subject based on the determined amount of the cell-free DNA not native to the subject.
At least one computer-readable storage medium storing computer-executable instructions that, when executed by at least one processor, cause a computing device to perform a method comprising:
- quantifying an amount of cell-free DNA extracted from a biological sample obtained from a recipient of a transplant;
- and
- determining a risk of a systemic disease in the recipient of a transplant based on the determined amount of the cell-free DNA.
At least one computer-readable storage medium storing computer-executable instructions that, when executed by at least one processor, cause a computing device to perform a method comprising:
- calculating a value for the Predictive Model of Formula 1, Formula 2 or Formula 3.
Dependencies are inferred from the claim text.