Methods and systems for detecting colorectal cancer via nucleic acid methylation analysis

Inventors

St. John, John • KOTHEN-HILL, Steven • Yang, Rui • Drake, Adam

Assignees

Freenome Inc

Abstract

The present disclosure provides methods and systems for screening or detecting a colorectal cancer or following colorectal disease progression that may be applied to cell-free nucleic acids such as cell-free DNA. The method may use detection of methylation signals within a single sequencing read in identified genomic regions as input features to train a machine learning model and generate a classifier useful for stratifying populations of individuals. The method may comprise extracting DNA from a cell-free sample obtained from a subject, converting the DNA for methylation sequencing, generating sequencing reads, and detecting colon proliferative cell disorder-associated signals in the sequencing information and training a machine learning model to provide a discriminator capable of distinguishing groups in a subject population such as healthy, cancer or distinguishing disease subtype or stage. The method may be used for, e.g., predicting, prognosticating, and/or monitoring response to treatment, tumor load, relapse, or colorectal cancer development.

Core Innovation

The disclosed technology provides a cell-free DNA methylation assay and classifier for colorectal cancer utilizing a panel of 20 hypermethylated genomic regions and locus-specific thresholds for methylated CpG sites. The classifier operates on normalized methylated-fragment counts, demonstrating an overall AUC of 0.949 with stage-specific AUCs of 0.905 for stage I and 0.998 for stage II. Background section details defining the underlying technical problem are not explicitly described in the provided material.

The claimed method identifies colorectal cancer based on methylated CpG-site counts exceeding predetermined thresholds in selected genomic regions following [procedural detail omitted for safety]. In response to identifying the cancer, the method administers a therapeutic intervention comprising chemotherapy, radiotherapy, immunotherapy, or surgery. The disclosure further encompasses monitoring treatment response, assessing disease stage and progression, and utilizing cancer-detection kits containing locus-selective probes and assay instructions.

Claims Coverage

The claim coverage includes four inventive features directed to identifying colorectal cancer from cell-free DNA methylation measurements and administering a therapeutic intervention in response.

The claim combines a selected cell-free DNA methylation-signature panel and locus-specific methylated CpG-site thresholds to identify colorectal cancer, followed by a specified therapeutic intervention.

Stated Advantages

Documented Applications