AGBT 2024

DNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding of biology. The interplay between genetics and the DNA epigenome orchestrates complex biological phenomena as diverse as cell fate, ageing, the response to environmental stimuli, and disease pathogenesis. Methods widely used in the detection of methylated cytosines fail to discriminate between thymines and unmodified cytosines. Consequently, they fail to capture common C-to-T transitions and provide incomplete genetic information. The duet multiomics solution is a new technology which sequences at single base resolution the complete genetic sequence integrated with modified cytosine. 

Liquid biopsy for profiling of cell free DNA (cfDNA) in blood holds huge promise to transform how we experience and manage cancer by early detection and identification of residual disease and subtype.  However, a standard blood draw yields an average of only 10 ng of cfDNA, of which DNA derived from the tumour is a small minority. Therefore, we are faced with a dilemma when utilising the limited sample to obtain maximum information.  

DNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding of biology. In human genomes, an epigenetic modification at the fifth carbon of cytosines bases comprises one fundamental pathway by which genes can be silenced or activated. Methods widely used to detect epigenetic modifications at cytosine bases rely on either deamination of unmodified cytosines to read as thymine or borane reduction of the modified oxidised cytosine bases to read as thymine. As a result, such methods fail to capture common C-to-T mutations, and importantly also fail to distinguish 5-methylcytosine (5mC – mainly found in silenced parts of the genome) from 5-hydroxymethylcytosine (5hmC – enriched in active gene bodies and enhancers). Hence, existing methods are unable to read the complete information stored in our genomes in a single workflow.