Abstract: Methods, systems, and software are provided for monitoring a cancer condition of a test subject. The method includes obtaining a liquid biopsy sample from the subject at a second time point, occurring after a first time point, containing cell-free DNA fragments. Low-pass whole genome methylation sequencing of the cell-free DNA fragments is performed to obtain nucleic acid sequences having a methylation pattern for a corresponding cell-free DNA fragment. The nucleic acid sequences are mapped to a location on a reference genome. Methylation metrics are determined based on the methylation patterns and mapped locations of the nucleic acid sequences. A circulating tumor fraction is estimated from the methylation metrics, and the estimate is compared to an estimate of the circulating tumor fraction for the test subject at the first time point.

Abstract: Methods, systems, and software are provided for monitoring a cancer condition of a test subject. The method includes obtaining a liquid biopsy sample from the subject at a second time point, occurring after a first time point, containing cell-free DNA fragments. Low-pass whole genome methylation sequencing of the cell-free DNA fragments is performed to obtain nucleic acid sequences having a methylation pattern for a corresponding cell-free DNA fragment. The nucleic acid sequences are mapped to a location on a reference genome. Methylation metrics are determined based on the methylation patterns and mapped locations of the nucleic acid sequences. A circulating tumor fraction is estimated from the methylation metrics, and the estimate is compared to an estimate of the circulating tumor fraction for the test subject at the first time point.

Abstract: Described herein are methods of assessing a sample-specific performance of a copy number variant model, a method for determining a copy number of an interrogated segment within a region of interest, and a method for determining a copy number variant abnormality within a region of interest. Sample-specific performance of the copy number variant caller is assessed by parameterizing a copy number variant model base on sequencing reads from a test sample, generating synthetic copy number variants using the sequencing read from the test sample, and calling the number of copies in the synthetic copy number variants using the copy number variant model and the sample-specific parameters. Calling a number of copies of an interrogated segment can include parameterizing a hidden Markov model using an analytic first derivative gradient and second derivative Hessian of one or more parameters in a copy number likelihood model.

Abstract: Methods for determining a respective carrier status of an individual are disclosed. In some examples, the method includes determining the respective carrier status based on copy number data for a gene in a genome of the individual and SNP data for the gene using a machine learning algorithm. In some examples, the machine learning algorithm is configured to receive, as inputs, the copy number data and the SNP data, and output the respective carrier status of the individual.