Just as an individual’s signature is unique and identifies him or her, the gene activity profile of a cell or tissue as shown on a microarray chip may be thought of as a unique, identifying molecular “signature” for that cell or tissue. If the cells or tissue used in a particular microarray analysis are disordered or diseased, the chip provides a signature for that disease. DNA microarrays are one of the most important developments in genomics to emerge since they serve as highly useful discovery tools for understanding gene function and interaction. The elucidation of specific disease signatures has potential diagnostic application in the hospital based laboratory medicine department.
GeneNews™ is able to generate disease-specific molecular signatures from a simple blood sample. It is important to emphasize that the Sentinel Principle identifies molecular signatures in blood that are markers of disease elsewhere in the body, for example, a colon tumor. A colon tumor elicits a response in the body that can include an immune response or inflammatory response. Those responses trigger gene expression changes that can be measured in blood using GeneNews technology. GeneNews diagnostic tests currently under development measure molecular signatures that are a reflection of disease in the body as detected in blood, not the gene expression of the colon tumor, for example, itself.
To obtain a molecular signature, the gene expression profiles from the blood samples of diseased patients are compared to the gene expression profiles from blood samples of control subjects without the disease in question. We use advanced microarray technology to identify those genes that are differentially expressed between the two groups; those genes represent the molecular signature that is a specific reflection of the disease under study. The genes within the molecular signature are then further characterized to identify a small set of genes for further validation in our Discovery Funnel process to allow small panels of genes to be generated for use in a reliable and reproducible diagnostic kit format.
In this way, GeneNews will enable the advancement of genomic medicine with tools that will unequivocally improve health, reduce disease, make better use of precious healthcare dollars and, most importantly, save lives.
FIGURE LEGEND: The above figure is a dendrogram from our neurological disorders study. A dendrogram is a visual representation of the gene expression levels of certain genes from a number of patients. This figure compares the gene expression profiles of subjects with schizophrenia, bipolar disorder and Alzheimer’s disease. The gene expression differences between the three patient types is obvious and helps form the basis for very exciting products that GeneNews is working diligently to perfect.
Molecular Signatures to Biomarkers
Early in our history, GeneNews scientists became aware that before molecular signatures for disease discovered in the research arena could reach their fullest potential in the diagnostic arena, some refinements to the technology were required.
One major problem we identified was a lack of readily available samples. Conventional microarray research studies rely on diseased tissue samples (and normal tissue as control material). It is often difficult, however to obtain appropriate samples. To study heart disease for example requires cardiac tissue, which can only be taken during heart transplant, during biopsy or after death. Some conditions are so rare that it is difficult to obtain enough samples for research. For example, ovarian cancer is an extremely serious diseases in need of further research at the microarray level. However with only 20,000 new cases in the US every year; it is difficult to obtain enough samples in order to perform the appropriate medical research.
The need is great however, to identify warning signals of incipient disease or early stage disease, when, especially in the case of cancer, it is generally most successfully treatable.
GeneNews scientists identified a simple, non-invasive, cost-effective molecular based method to identify early stage disease and address the problems described above. GeneNews' standard procedure, based on the Sentinel Principle, was developed to take advantage of molecular signatures identified using microarrays and is not limited due to lack of tissue samples, The Sentinel Principle is vitally important to the advancement of genomics from the research to the clinical arena.