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US 2025/0027156 A1Published application
Methods and systems for detection of abnormal karyotypes
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsEvan Maxwell, Lukas Habegger, Jeffrey Reid
Life of this patent
Estimating the term…
Abstract
Methods and systems for detecting abnormal karyotypes are disclosed. An example method can comprise determining read coverage data, allele balance distributions of heterozygous SNPs, and chromosomal segments where heterozygosity is not observed. The methods and systems can then determine one or more metrics which can be indicative of abnormal karyotype(s).
Claims20
A method comprising:
- receiving population-scale whole-exome sequencing data associated with a plurality of biological samples;
- determining, for a chromosome associated with a biological sample of the plurality of biological samples, based on the population-scale whole-exome sequencing data, a deviation between a measured exome-wide ratio of read coverage data for that chromosome and an expected exome-wide ratio of read coverage data for that chromosome;
- detecting, based on the deviation between the measured exome-wide ratio of read coverage data and the expected exome-wide ratio of read coverage data, a read coverage anomaly for that chromosome indicative of chromosomal abnormality;
- determining, for the at least one chromosome, based on a proportion of sequencing reads from the population-scale whole-exome sequencing data supporting each allele at heterozygous sites of the at least one chromosome, at least one allele balance metric indicative of allele balance distribution;
- detecting, based on a deviation between the at least one allele balance metric and at least one expected allele balance metric, an allele balance anomaly indicative of chromosomal abnormality for that chromosome;
- and
- reporting, based on the read coverage anomaly and the allele balance anomaly, an abnormal karyotype in the biological sample of the plurality of biological samples.
4 more elements
One or more non-transitory computer-readable media storing processor-executable instructions that, when executed by a processor, cause the processor to:
- receive population-scale whole-exome sequencing data associated with a plurality of biological samples;
- determine, for a chromosome associated with a biological sample of the plurality of biological samples, based on the population-scale whole-exome sequencing data, a deviation between a measured exome-wide ratio of read coverage data for that chromosome and an expected exome-wide ratio of read coverage data for that chromosome;
- detect, based on the deviation between the measured exome-wide ratio of read coverage data and the expected exome-wide ratio of read coverage data, a read coverage anomaly for that chromosome indicative of chromosomal abnormality;
- determine, for the at least one chromosome, based on a proportion of sequencing reads from the population-scale whole-exome sequencing data supporting each allele at heterozygous sites of the at least one chromosome, at least one allele balance metric indicative of allele balance distribution;
- detect, based on a deviation between the at least one allele balance metric and at least one expected allele balance metric, an allele balance anomaly indicative of chromosomal abnormality;
- and
- report, based on the read coverage anomaly and the allele balance anomaly, an abnormal karyotype in the biological sample of the plurality of biological samples.
4 more elements
A system comprising:
- a computing device configured to:
- receive population-scale whole-exome sequencing data associated with a plurality of biological samples;
- determine, for a chromosome associated with a biological sample of the plurality of biological samples, based on the population-scale whole-exome sequencing data, a deviation between a measured exome-wide ratio of read coverage data for that chromosome and an expected exome-wide ratio of read coverage data for that chromosome;
- detect, based on the deviation between the measured exome-wide ratio of read coverage data and the expected exome-wide ratio of read coverage data, a read coverage anomaly for that chromosome indicative of chromosomal abnormality;
- determine, for the at least one chromosome, based on a proportion of sequencing reads from the population-scale whole-exome sequencing data supporting each allele at heterozygous sites of the at least one chromosome, at least one allele balance metric indicative of allele balance distribution;
- detect, based on a deviation between the at least one allele balance metric and at least one expected allele balance metric, an allele balance anomaly indicative of chromosomal abnormality;
- report, based on the read coverage anomaly and the allele balance anomaly, an abnormal karyotype in the biological sample of the plurality of biological samples;
- and
- a user device configured to display an output of the reported abnormal karyotype.
6 more elements
Dependencies are inferred from the claim text.