Methods and systems for tumor detection

A method of non-invasively detecting a tumor in a subject, comprising:

• obtaining, through a non-invasive procedure, a first biological sample from the subject, wherein the first biological sample comprises substantially cell-free DNA (cfDNA) derived from normal cells and comprises or is suspected of comprising tumor-derived cfDNA;
• performing a first assay using the first biological sample, wherein the first assay has a sensitivity for a first set of markers indicative of the tumor, and wherein the first assay comprises:
• measuring a methylation status of the tumor-derived cfDNA in the first biological sample;
• and
• determining if the first biological sample includes the first set of markers indicative of the tumor based on a comparison of the methylation status of the tumor-derived cfDNA in the first biological sample to at least one first calibration value;
• responsive to determining that the first biological sample includes the first set of markers indicative of the tumor, obtaining, through a non-invasive procedure, a second biological sample from the subject, wherein the second biological sample comprises cfDNA derived from normal cells and comprises or is suspected of comprising tumor-derived cfDNA;
• only when the first biological sample includes the first set of markers indicative of the tumor, performing a second assay using the second biological sample, wherein the second assay has a specificity for a second set of markers indicative of the tumor, and wherein the second assay comprises:
• measuring a methylation status of the tumor-derived cfDNA in the second biological sample;
• identifying the tumor in the subject based on the comparison of the methylation status of the tumor-derived cfDNA in the second biological sample to at least one second calibration value;
• and
• outputting a report indicative of the tumor in the subject.