HyperGenomics^TM

HyperGenomics^TM is an epigenetic platform for differential prognostic and personalized medicine diagnostic products for cancer.

HyperGenomics^TM 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 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^TM for cancer diagnostics.

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

The HyperGenomics^TM 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 type technique.

Hypergenomics

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

Nucleosomics^TM

Is a platform for non-invasive (blood) tests for early cancer diagnosis based on epigenetic signal changes associated with malignancy.

The control of gene expression is determined by a number of different epigenetic regulatory mechanisms. Paramount amongst these is the chromatin environment surrounding the gene and key covalent modifications (including acetylation, methylation, phosphorylation and others) to the histone proteins associated with the nucleosomes of the gene. This is often referred to as the histone code.

Disruption of the normal histone code is associated with aberrant gene expression and malignant transformation and these alterations are the basis of Nucleosomics.

Nucleosomics is non-invasive. Intact nucleosomes derived from tumour chromatin are found in the blood of cancer patients, but not in healthy individuals. These cell free nucleosomes can be analyzed for global histone code modifications that are characteristic of cancers. The presence in the blood of nucleosomes associated with particular global histone modifications is diagnostic of cancers.