The deciphering of the human genome provides a milestone in our ability to apply this new information to medical science. At present response to therapeutic intervention remains quite undefined and imprecise. The ability to deliver the right dose of medicine for the right patient remains an intensive research area within academic medical centers, translational research institutes and within pharmaceutical companies. The science of the investigation of the relationship between genomic variation and drug response- pharmacogenomics - is becoming an increasingly important part of drug development.

Pharmacogenomics holds many promises including:

• Improved treatment of disease by using more effective drugs and safer prescribing regimens.

• Defining responders and non-responders to better define the most appropriate group in which to target a given treatment.

• Improving our understanding of the underlying biology of disease.

Exploratory pharmacogenomics research focuses on the retrospective investigation of genomic factors associated with variations in patient responses, pharmacokinetic differences and potential adverse side effects which may occur during the course of therapy. The use of RNA expression continues to be used by many researchers to explore the underlying genomic factors which influence these variations, revealing new insight into genes and pathways involved. Genomic Signature Sequencing (GSS)™ provides the researcher with the necessary throughout and quantitative accuracy to allow the design and execution of large patient cohort studies needed to explore the genomic factors influencing drug response and develop robust statistical analyses. From these analyses RNA expression signatures which appear to represent the differential effects of drug response can be further examined in subsequent clinical studies to provide validation of the initial exploratory findings.

The Helicos™ GSS application will allow:

• The development of exploratory genomic signatures indicative of differential drug response and/or safety

• The ability to apply these findings for validation of the genomic signature

• Provide a research tool to enable upfront analyses of RNA profiles to allow patient selection based on RNA profiles in a timely and cost-effective manner