Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12456541-B2
Publication Date
2025-10-28
Expiration Date
Abstract
Methods and systems for analyzing genetic variants are disclosed. The methods and systems can be used to classify a variant in a tumor sample as germline, somatic, subclonal, or ambiguous. The variant can be classified by fitting a genome-wide copy number model to a sequence coverage input and a SNP allele frequency input. The fitted model can be used to determine a tumor purity, and a total copy number and a minor allele copy number for each of a plurality of genomic segments. Using the tumor purity, the total copy number and the minor allele copy number for the genomic segment comprising the variant, and the variant allele frequency for the variant in the tumor sample, the variant can be classified as germline, somatic, subclonal or ambiguous.
Core Innovation
The disclosed system and methods classify a variant in a tumor sample as germline, somatic, subclonal, or ambiguous without using a sample-matched normal control. They receive sequence coverage, SNP allele frequency, and variant allele frequency inputs, fit a genome-wide copy number model, and use tumor purity and segment total and minor allele copy numbers together with variant allele frequency to classify the variant.
The disclosed approach addresses variant classification without a sample-matched normal control for clinical interpretation and treatment selection. Based on the characterization of the variant as germline, somatic, or subclonal, a treatment recommendation for a selected treatment modality is generated. The method further provides for treating the subject with the selected treatment modality.
Claims Coverage
The independent claims comprise claims 1, 15, and 29, covering a system for variant classification, a method for variant classification, and a method of treating a subject with a tumor, comprising 6 inventive features.
Inputs obtained without a sample-matched normal control
The system and methods receive sequence coverage, SNP allele frequency, and variant allele frequency inputs for the tumor sample, determined without using a sample-matched normal control.
Genome-wide copy number model
A genome-wide copy number model for the tumor sample is fitted to the sequence coverage and SNP allele frequency inputs.
Tumor purity and segment copy numbers
Based on the model, tumor purity, total copy number, and minor allele copy number are determined for genomic segments, including a segment containing the variant.
Variant classification
The variant is classified as germline, somatic, subclonal, or ambiguous using tumor purity, the segment copy numbers, and variant allele frequency.
Treatment recommendation
The method generates a recommendation of a selected treatment modality based at least on characterization of the variant as germline, somatic, or subclonal.
Treatment with the selected modality
The subject is treated with the selected treatment modality.
The independent claims cover variant classification from tumor-sample data without a sample-matched normal control, using a genome-wide copy number model and variant allele frequency. The treatment claim additionally covers generating a treatment recommendation from the variant characterization and treating the subject with the selected modality.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Clinical interpretation of tumor variants, including classification as germline, somatic, subclonal, or ambiguous, across tissue samples, blood samples, and blood constituent samples.
Treatment selection based on characterization of a tumor variant; the treatment method generates a recommendation of a selected treatment modality and treats the subject with that modality.
Interested in licensing this patent?