The Helicos™ Genetic Analysis System provides a single unifying platform to allow researchers to interrogate the genome. Helicos is developing the Genomic Signature Sequencing (GSS)™ application for use on the Helicos Genetic Analysis System to quantitatively measure the expression of subsets of genes across tens of thousands of samples - at a per target price that is an order of magnitude lower then any other RNA methodology. The sheer throughput, cost, and information-rich nature of the readout has the potential to transform disease knowledge and impact drug discovery and development.

Background

The Human Genome Project has provided an enormous wealth of genomic information, most of which has yet to be leveraged in the discovery of new, innovative approaches to healthcare. The scientific community remains challenged with elucidating the function of the expressed genome to fully translate this information into knowledge which will provide a more complete understanding of disease and new treatment opportunities. It becomes critical to determine which subsets of genes are involved in disease states, an individual's response to therapy or the likelihood that a patient will exhibit a side-effect from therapeutic intervention. This is complicated by the fact that of the hundreds to thousands of differentially regulated genes, only a small percentage may actually contribute to disease or to the physiological state in question. However, we are beginning to understand that these contributing genes produce a pattern - or transcriptional fingerprint - based on their differential expression which when studied can provide avenues to the elucidation of gene function.

Researchers often use microarray technology or various other methodologies to develop a global tissue or cellular RNA profile. From this RNA profile, unique subsets of genes associated with biological states can be determined and an RNA signature which classifies this biological state defined. These gene signatures can be compared across a wide array of biological samples to investigate numerous hypotheses. This work is further extended to develop a reproducible genomic signature which is indicative of the cellular differentiation state, a particular disease state, therapeutic response or to better molecularly characterize a tumor. This research is only limited by scientist's access to cost-effective, high-throughput methodologies which allow the interrogation of the multitude of important biological questions waiting to be asked.

Helicos has developed an assay, Genomic Signature Sequencing, to interrogate a subset of these transcriptional signatures of interest to the researcher.

Applications

Key applications for this approach include:

• Gene Expression High Throughput Screening (GE-HTS)
• Drug Development
• Pharmacogenomics