US 2024/0177802 A1 · ACCURATELY PREDICTING VARIANTS FROM METHYLATION SEQUENCING DATA

Abstract

This disclosure describes methods, non-transitory computer readable media, and systems that can utilize methylation sequencing assay data to generate genotype calls efficiently and accurately for a target genomic sample. In some implementations, the disclosed system identifies the target genomic sample's nucleotide reads comprising nucleobases converted by a methylation sequencing assay. The disclosed system can determine variant calls based on aligning the nucleotide reads with a reference genome. To account for errors introduced by the methylation sequencing assay, in some cases, the disclosed system corrects or modifies genotype-likelihood metrics for a subset of candidate variant calls. The disclosed system further imputes genotype calls based on such modified genotype-likelihood metrics and a comparison of a subset of variant calls with marker variants from a reference panel.

Claims20

Dependent claims

A method comprising:

identifying, for a target genomic sample, nucleotide reads comprising one or more nucleobases converted by a methylation sequencing assay;
determining variant calls for the target genomic sample based on an alignment of the nucleotide reads with a reference genome;
accessing a reference panel comprising marker variants for different haplotypes corresponding to a target genomic region of the target genomic sample;
and
imputing one or more genotype calls for the target genomic sample based on a comparison of a subset of variant calls for the target genomic sample and the marker variants from the reference panel.

2 more elements

A system comprising:

at least one processor;
and
a non-transitory computer-readable medium comprising instructions that, when executed by the at least one processor, cause the system to:
identify, for a target genomic sample, nucleotide reads comprising one or more nucleobases converted by a methylation sequencing assay;
determine variant calls for the target genomic sample based on an alignment of the nucleotide reads with a reference genome;
access a reference panel comprising marker variants for different haplotypes corresponding to a target genomic region of the target genomic sample;
and
impute one or more genotype calls for the target genomic sample based on a comparison of a subset of variant calls for the target genomic sample and the marker variants from the reference panel.

5 more elements

A non-transitory computer-readable medium storing instructions that, when executed by at least one processor, cause a computing device to:

identify, for a target genomic sample, nucleotide reads comprising one or more nucleobases converted by a methylation sequencing assay;
determine variant calls for the target genomic sample based on an alignment of the nucleotide reads with a reference genome;
access a reference panel comprising marker variants for different haplotypes corresponding to a target genomic region of the target genomic sample;
and
impute one or more genotype calls for the target genomic sample based on a comparison of a subset of variant calls for the target genomic sample and the marker variants from the reference panel.

2 more elements

Dependencies are inferred from the claim text.

Accurately predicting variants from methylation sequencing data

Life of this patent

Accurately predicting variants from methylation sequencing data

Life of this patent

Abstract

Claims20