NCI Creates Gene Expression Database of
Normal Human Organ Tissue
Researchers at the National Cancer Institute (NCI) Center for Cancer Research (CCR) today unveiled a publicly available Web site that provides a detailed catalogue of the genes that are actually expressed in most of the body's major organs. The database, also discussed in the March Genome Research, offers a one-of-a-kind tool that all cancer researchers can use to better define potential drug targets and anticipate their impact elsewhere in the human biosystem.
"The Normal Organ Database democratizes access to information that many, until recently, considered esoteric data for geneticists only," says Dr. Javed Khan, leader of CCR's Pediatric Oncology Branch oncogenomics team that developed the database. Today gene expression profiles are becoming widely available and widely used, Dr. Khan continues, in part because microarray technology now lets researchers run high-throughput assays for thousands of genes at once. "The challenge now is to isolate meaningful results for small numbers of specific genes within these large datasets," he adds. "More intuitively, one needs a true working definition of 'normal' against which to measure disease. This tool makes this far easier." Use of the database (http://home.ccr.cancer.gov/oncology/oncogenomics) is not limited to cancer biologists, but is also open to those involved in developing new drugs for a wide range of diseases such as heart disease and autoimmune disorders. It may elucidate the pathological processes in these diseases as well.
Each of the 19 organs tested in the Genome Research study revealed a distinctive expression pattern or genetic fingerprint, even though the sources of human postmortem tissue samples used in the study were biologically diverse. By using so many samples (158) from many different regions of each organ, Dr. Khan's team engineered a generic database that is statistically sound. "Remarkably," says Dr. Khan, "any truly random subset of 1,000 genes will distinguish one organ from another."
With this baseline of normal gene expression for a given organ now accessible on the Web site, researchers should be able to more effectively analyze tissue samples from their own work. For example, Dr. Khan's work has largely focused on neuroblastoma (NB). Using the organ database, the research team detected and identified 19 highly expressed genes from their own NB samples that seem to be crucial to the biology of the NB carcinogenic process. This information now can inform clinicians of potential "druggable" targets.
The CCR team then took that same data one step further, trying to actually predict outcomes for particular patients based only on gene expression. "Using a sophisticated computer program that relies on artificial neural networks, the team analyzed NB expression profiles from the database and developed a patentable prognostic tool that improves on the current prognosis standard in the field, developed by NCI and the Children's Oncology Group," Dr. Khan said.
"I expect this new searchable database to be heavily used by the scientific community," predicts Dr. Paul Meltzer, Molecular Genetics section chief of the Cancer Genetics Branch at the National Human Genome Research Institute. "Because now any user can extract information relevant to their own scientific interests without having to consult an expert in microarray data analysis."
The normal organ database used cDNA microarrays to profile genes. For those researchers whose data was derived from Affymetrix chips or oligonucleotide arrays, Dr. Khan intends soon to provide transformation matrices that will make the datasets fully compatible.
By Addison Greenwood