Sample Validation for Cancer Classification

A method for validating that a cell-free deoxyribonucleic acid (cfDNA) sample is from a test subject, the method comprising:

• obtaining a test sample from a test subject, wherein the test sample is reported to be one or more reported ethnicities of a plurality of ethnicities;
• obtaining the cfDNA sample from the test subject;
• obtaining a plurality of sequence reads from the cfDNA sample, the plurality of sequence reads including a plurality of single nucleotide polymorphisms (SNPs);
• determining from the plurality of sequence reads, an allele frequency for each of the plurality of SNPs;
• obtaining expected allele frequencies for each of the plurality of SNPs for each of the plurality of ethnicities determined from a training set, wherein the ethnicity is known for each training sample in the training set;
• for each chromosome of a plurality of chromosomes:
• calculating an ethnicity probability for each of the plurality of ethnicities based on the determined allele frequencies for a subset of SNPs within the chromosome and the expected allele frequencies for the plurality of ethnicities for the subset of SNPs within the chromosome;
• predicting one or more ethnicities for the cfDNA sample based on the calculated ethnicity probabilities for the plurality of chromosomes;
• and
• validating that the cfDNA sample is from the test subject based on the one or more predicted ethnicities of the cfDNA sample and the one or more reported ethnicities of the test subject.

A method for validating that a cell-free deoxyribonucleic acid (cfDNA) sample is from a test subject, the method comprising:

• obtaining a test sample from a test subject, wherein an age of the test subject is reported to be within one of a plurality of age ranges;
• receiving the cfDNA sample from the test sample;
• obtaining sequence reads from the cfDNA sample;
• for each of a plurality of CpG sites, determining a methylation density at each of the plurality of CpG sites based on the sequence reads from the cfDNA sample;
• predicting an age range for the cfDNA sample by applying a trained regression model to the determined methylation densities for the plurality of CpG sites, wherein the trained regression model is trained using a training set where the methylation density for each of the plurality of CpG sites and an age is known for each individual of the training set;
• validating that the cfDNA sample is from the test subject based on the predicted age range of the cfDNA sample and the reported age range of the test subject.

A method for validating that a cell-free deoxyribonucleic acid (cfDNA) sample is from a test subject, the method comprising:

• obtaining a test sample from a test subject, wherein two or more of a biological sex, an ethnicity, and an age within one of a plurality of age ranges have been reported for the test subject;
• obtaining the cfDNA sample from the test sample;
• obtaining a plurality of sequence reads from the cfDNA sample;
• predicting for the cfDNA sample two or more of:
• a biological sex for the cfDNA sample based on:
• a first count of sequence reads for a first gene found on an X chromosome of the human genome and not found on a Y chromosome of the human genome, and
• a second count of sequence reads for a second gene found on the Y chromosome and not found on the X chromosome;
• one or more ethnicities for the cfDNA sample based on ethnicity probabilities calculated for each chromosome of a plurality of chromosomes, the ethnicity probabilities for a given chromosome based on an allele frequency determined from the sequence reads of the cfDNA sample for each of a plurality of SNPs on the given chromosome;
• and
• an age range for the cfDNA sample based on a methylation density determined for each of a plurality of CpG sites;
• and
• validating that the cfDNA sample is from the test subject based on a comparison of two or more of the predicted biological sex of the cfDNA sample, the one or more predicted ethnicities of the cfDNA sample, the predicted age range of the cfDNA sample and two or more of the reported biological sex, the reported ethnicity, and the reported age range of the test subject.

A method for validating that a cell-free deoxyribonucleic acid (cfDNA) sample is from a test subject, the method comprising:

• obtaining a test sample from a test subject, wherein a biological sex and an ethnicity have been reported for the test subject;
• obtaining the cfDNA sample from the test sample;
• obtaining a plurality of sequence reads from the cfDNA sample;
• predicting for the cfDNA sample:
• a biological sex for the cfDNA sample based on:
• a first count of sequence reads for a first gene found on an X chromosome of the human genome and not found on a Y chromosome of the human genome, and
• a second count of sequence reads for a second gene found on the Y chromosome and not found on the X chromosome;
• and
• one or more ethnicities for the cfDNA sample based on ethnicity probabilities calculated for each chromosome of a plurality of chromosomes, the ethnicity probabilities for a given chromosome based on an allele frequency determined from the sequence reads of the cfDNA sample for each of a plurality of SNPs on the given chromosome;
• and
• validating that the cfDNA sample is from the test subject based on a comparison of the predicted biological sex of the cfDNA sample and the one or more predicted ethnicities of the cfDNA sample to the reported biological sex and the reported ethnicity of the test subject.

A method for validating that a cell-free deoxyribonucleic acid (cfDNA) sample is from a test subject, the method comprising:

• obtaining a test sample from a test subject, wherein a biological sex and an age within one of a plurality of age ranges have been reported for the test subject;
• obtaining the cfDNA sample from the test sample;
• obtaining a plurality of sequence reads from the cfDNA sample;
• predicting for the cfDNA sample:
• a biological sex for the cfDNA sample based on:
• a first count of sequence reads for a first gene found on an X chromosome of the human genome and not found on a Y chromosome of the human genome, and
• a second count of sequence reads for a second gene found on the Y chromosome and not found on the X chromosome;
• and
• an age range for the cfDNA sample based on a methylation density determined for each of a plurality of CpG sites;
• and
• validating that the cfDNA sample is from the test subject based on a comparison of the predicted biological sex of the cfDNA sample and the predicted age range of the cfDNA sample to the reported biological sex and the reported age range of the test subject.

A method for validating that a cell-free deoxyribonucleic acid (cfDNA) sample is from a test subject, the method comprising:

• obtaining a test sample from a test subject, wherein an ethnicity and an age within one of a plurality of age ranges have been reported for the test subject;
• obtaining the cfDNA sample from the test sample;
• obtaining a plurality of sequence reads from the cfDNA sample;
• predicting for the cfDNA sample:
• one or more ethnicities for the cfDNA sample based on ethnicity probabilities calculated for each chromosome of a plurality of chromosomes, the ethnicity probabilities for a given chromosome based on an allele frequency determined from the sequence reads of the cfDNA sample for each of a plurality of SNPs on the given chromosome;
• and
• an age range for the cfDNA sample based on a methylation density determined for each of a plurality of CpG sites;
• and
• validating that the cfDNA sample is from the test subject based on a comparison of the one or more predicted ethnicities of the cfDNA sample and the predicted age range of the cfDNA sample to the reported ethnicity and the reported age range of the test subject.