HyperGenomics^TM

HyperGenomics is an epigenetic platform for differential, prognostic and personalised medicine diagnostic products for cancer.

HyperGenomics yields information about the epigenetic regulation of genes by hypersensitive site mapping in any tissue or cell type and can be used on a global genome scale.

Human cells contain about 2 metres of DNA encoding some 30,000 genes. The DNA is efficiently packaged in chromatin - a complex protein-DNA structure composed of coils of nucleosomes that run along the length of the DNA in a “beads on a string” arrangement.

Hypersensitive sites are lengths of a few hundred base pairs of naked DNA in the chromosomes where areas the chromatin structure (one or more nucleosomes) has been removed.

The presence and position of hypersensitive sites in a person’s chromosomes is an epigenetic signal for each cell, allowing access by the cell’s transcription machinery to specific genes and “instructing the cell to read” the particular gene or not. Disruption of epigenetic signaling mechanisms is one of the earliest events in cancer and ValiBIO is developing HyperGenomics for cancer diagnostics.

The basis of HyperGenomics is to highly accurately identify tumours and tumour subtypes from the pattern of hypersensitive sites in the cells.

The HyperGenomics platform is used for:

1. Genome wide screening to identify all the hypersensitive sites present in cancer or healthy tissue cells. Using ultra-sequencing all the hypersensitive sites present in several patient samples can be screened in a single run. This technique is used to identify panels of hypersensitive sites present in aggressive malignant cancer cells but absent in other cells.

The technique involves:

• extraction of cellular chromatin. This is a standard procedure for which automated equipment is available.
• Nuclease digestion of the chromatin
• Extraction of the DNA from the digested chromatin
• Identification of the resultant fragments, for example by ultra-sequencing

2. Testing patient samples for the presence of particular hypersensitive sites identified as being of interest by genome wide screening using a low cost, rapid and high-throughput PCR technique.

Hypergenomics

• produces a binary result
• is extremely sensitive
• can be used to investigate heterogeneous cell samples
• can be automated