Background

Epigenetics represents a new frontier in cancer research. The epigenetic information in the genome provides regulation of transcription and can vary from cell to cell. While there are many types of epigenetic processes — such as methylation, acetylation, and phosphorylation — the best known process, and the one most studied, is methylation.

Methylation occurs when a methyl group is added to the fifth position of cytosine within a CpG dinucleotide. This process in some instances, through gene expression regulation, has been shown to be linked to disease states such as cancer. Methylation can give rise to imprinting, where one of the two alleles in a gene pair is silenced. The silencing of one allele may present a problem if the other allele is damaged and that gene serves a protective function, such as the beneficial effect of a tumor suppressor gene, in the organism.

Methylation patterns in the genome are currently under investigation by many laboratories studying both common disease and oncology. The commonality of patterns across samples belonging to a particular phenotype may constitute a signature that is linked to the trait or disease in question. In order to uncover these patterns and definitively link the patterns to a certain phenotype, a statistically relevant amount of samples needs to be studied across a large amount of CpG islands in the genome to provide enough genomic coverage. Short of sequencing the entire genome, researchers must have an efficient way to capture CpG islands as well as high enough sequencing throughput to interrogate enough genomic areas of interest to provide a sufficiently dense enough coverage across the genome.

Application

Elucidating the role of methylation in genome regulation has been limited by the low throughput and high cost of current sequencing technologies. Helicos will utilize its candidate gene capture method to allow scientists to select CpG islands of interest from the genome and investigate their methylation status.

Advantages of this approach include:

• The high level of specificity and multiplexing associated with the candidate gene capture assay will provide an efficient means for providing a statistically significant amount of regions across a large number of samples.
• Follow up on these captured regions with bisulfite treatment and subsequent high throughput sequencing will allow the interrogation of methylated cytosines and the discovery of methylation patterns at an unprecedented rate.
• In order to assess the state of transcriptional binding sites, Helicos can also sequence the products of Chromatin Immmunoprecipation (ChIP).

Helicos will enable the capture of CpG islands via its candidate region capture method. Our straightforward sample preparation method provides unprecedented multiplexing without the need for amplification.

For more information on epigenetics or methylation, please contact collaborations@helicosbio.com