Early lung cancer detection by dna methylation phenotyping of sputum-derived cells

A method, comprising:

• obtaining a biological sample from a subject, the biological sample including a plurality of cells;
• determining (i) a global 5-methylcytosine (5mC) content and (ii) a spatial nuclear co-distribution of 5mC and global DNA (gDNA) in a nucleus of each of the plurality of cells;
• determining that a cell of the plurality of cells is hypomethylated if at least the global 5mC content or the spatial nuclear co-distribution of 5mC and gDNA in the nucleus of the cell is significantly different from one or more non-cancerous or non-precancerous reference cells;
• and
• based at least in part on a percentage of determined hypomethylated cells in the plurality of cells exceeding a threshold, determining that the subject has a high risk of developing clinically verifiable cancer.