Abstract: This disclosure describes methods, non-transitory-computer readable media, and systems that can simultaneously determine estimated methylation-level values for cytosine bases and genotype calls for a target genomic sample. The disclosed system can utilize a Bayesian method on a target genomic sample's nucleotide-read data to generate estimated methylation-level values that indicate genomic coordinates at which the target genomic sample comprises a reference cytosine base or a nucleobase that could be called as a cytosine. The disclosed system can estimate methylation-level values based on prior genotype probabilities and observed nucleobases at a genomic coordinate from a read pileup of a target genomic sample. Based on the estimated methylation-level values and base-call-quality metrics, the disclosed system may generate posterior genotype probabilities for the genomic sample at the genomic coordinate.

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.

Abstract: This disclosure describes methods, non-transitory computer readable media, and systems that can use a computationally efficient model to determine a corrected methylation-level value for a specific sample nucleotide sequence. For instance, the disclosed systems determine a false positive rate and a false negative rate at which a given methylation sequencing assay converts cytosine bases. Based on the determined false positive rate and false negative rate, the disclosed systems determine a corrected methylation-level value that corrects for a bias of the given methylation sequencing assay.