Abstract: The present disclosure provides methods and systems for nucleic acid sequencing. Such systems and methods may use a single flow cell to perform unbiased and/or biased sequencing to generate libraries of nucleic acid molecules. An aspect of the present disclosure provides a method for increasing complexity of a sample for sequencing, the method comprising: providing a first nucleic acid sample having a first degree of complexity that differs from a desired degree of complexity; providing a second nucleic acid sample having a second degree of complexity that differs from the first degree of complexity and that differs from the desired degree of complexity; pooling at least a portion of the first nucleic acid sample and at least a portion of the second nucleic acid sample, thereby generating a pooled nucleic acid sample having the desired degree of complexity; and sequencing at least a portion of the pooled nucleic acid sample.

Abstract: The present disclosure provides methods of assessing tumor status (e.g., progression, regression, recurrence, etc.) in a subject. In an aspect, a method for assessing tumor status (e.g., progression, regression, recurrence, etc.) of a subject may comprise: based on first and second WGS data of cfDNA molecules of a subject at different time points, determing (i) a first and second plurality of CNAs and (ii) a first and a second plurality of fragment lengths; processing the first and second plurality of CNAs to determine a CNA profile change; comparing the first and second plurality of fragment lengths to determine a fragment length profile change; determining a first or second tumor fraction of the subject at the first or second timepoint, based at least in part on the CNA profile change and the fragment length profile change; and detecting a tumor status of the subject based at least in part on the first or second tumor fraction.

Abstract: The invention disclosed herein generally relates to methods of assessing microsatellite instability in a subject. In an aspect, the present disclosure provides a computer-implemented method of assessing microsatellite instability of a subject, comprising: obtaining a quantitative measure of a plurality of microsatellite repeat elements from a blood sample of a subject; processing the plurality of quantitative measures to obtain a statistical measure of deviation of the plurality of quantitative measures; and detecting a presence of the microsatellite instability (MSI) of the subject when the statistical measure of deviation of the plurality of quantitative measures satisfies a predetermined criterion, or detecting an absence of the microsatellite instability (MSI) of the subject when the statistical measure of deviation of the plurality of quantitative measures does not satisfy the predetermined criterion.

Abstract: The present disclosure provides methods and systems for nucleic acid sequencing. Such systems and methods may use a single flow cell to perform unbiased and/or biased sequencing to generate libraries of nucleic acid molecules. An aspect of the present disclosure provides a method for increasing complexity of a sample for sequencing, the method comprising: providing a first nucleic acid sample having a first degree of complexity that differs from a desired degree of complexity; providing a second nucleic acid sample having a second degree of complexity that differs from the first degree of complexity and that differs from the desired degree of complexity; pooling at least a portion of the first nucleic acid sample and at least a portion of the second nucleic acid sample, thereby generating a pooled nucleic acid sample having the desired degree of complexity; and sequencing at least a portion of the pooled nucleic acid sample.

Abstract: The present disclosure provides methods for fingerprinting of biological samples of a subject.