Non-invasive disease detection and monitoring

Abstract

The present invention provides a method of analysing a sample obtained from a subject having or suspected of having a somatic disease state, the method comprising: (a) providing a tissue, proximal or distal sample of limited quantity, such as a cell-free DNA (cfDNA)-containing sample obtained from the subject and performing methylation sequencing of at least 10 predetermined genomic regions, wherein said methylation sequencing may comprise a non-destructive, enzyme-based conversion method to differentiate unmethylated cytosine from 5-methylcytosine and/or 5-hydroxymethylcytosine; (b) generating metrics from the methylation sequencing reads in step (a) that represent one or both of (i) a measure of the degree to which the methylation observed within a sequencing read is similar to a previously determined disease methylation signal, said measure comprising a read rating generated by providing a vector of methylation states for each methylation sequencing read and summing the information content of all methylation states that are concordant with the methylation state for the same region previously determined in a one or more disease samples; and (ii) a measure of intra-read methylation heterogeneity; and (c) integrating the metrics generated in step (b) across the at least 10 predetermined genomic regions to obtain a global measure of disease-originating cfDNA in the sample obtained from the subject. Related methods and systems for use in performing the methods are also provided.

Dependencies are inferred from the claim text.