DNA structure [Illustrative].
(photo credit: INIMAGE)
A Hebrew University of Jerusalem team working with researchers from Massachusetts General Hospital in Boston have created an algorithm that makes it possible to scan potentially millions of genetic sequences from plants, viruses, bacteria and animals for links – almost as easily as performing a Google search.
Dr. Yuval Tabach, a molecular biologist and researcher from HU’s Faculty of Medicine’s Institute for Medical Research Israel-Canada, has developed a system to allow any investigator, physician or patient to analyze a gene according to its evolutionary profile. The research paper was just published in the journal Nucleic Acids Research.
The Israel-American team said the database and Internet tool will “change the face of biomedical research by creating the ability to identify unique disease-related genes and predict their biological functions.
Doing so,” they continued, “opens the door to drug repositioning, which holds the promise of new treatments for genetic diseases or cancer.”
The technique, said Tabach, “is simple and based on the fact that genes that work together or those that play an important role in biology will be present together in organisms that need them. Conversely, genes connected to a particular function like vision will disappear from species that have lost the power of sight [like cave fishes or moles], and may therefore be identified by a comparison to the genes in normal animals.”
The application is a product of Tabach’s continuing research that he began as a fellow at Harvard University in collaboration with researchers and physicians from all over the world. This research revealed the possibility of comparing the evolutionary profiles derived from multiple organisms to predict the biological functions and clinical relevance of given genes.
One example of a known mutation that increases the likelihood of developing breast and ovarian cancers is in the BRCA1 gene. Interest in this gene was highlighted when, in 2013, American actress and director Angelina Jolie – having discovered that she had inherited the dangerous mutation from her mother who died of cancer at age 56 – decided to undergo a preventative double mastectomy.
However in the majority of cases, both for breast cancer and other genetically transmitted diseases, the identity of the gene responsible is unknown.
By using the methods of genetic analysis developed by Tabach, researchers can now identify genes within the same network as the BRCA1 gene or other associations of genes simply by scanning the evolutionary profiles of dozens of organisms with a single click.
The number of organisms that can be scanned in this way is anticipated to increase to hundreds in the near future.
“The significance of this tool is that anyone, physician or researcher, can input results from genetic mapping studies concerning suspected genes, and the tool will identify evolutionary, and probably functional, connections to known genes with association to diseases,” explained Tabach. “The process is rapid, without cost or time wasted, and enables the identification of genes responsible even for rare genetic diseases.”
An interesting example of a gene that could be identified using this phylogenetic profiling approach is the so-called “Vampire’s Disease,” known to doctors as porphyria. Representing a family of genetic diseases characterized by abdominal pain, sensitivity to sunlight, purple urine and psychotic episodes, porphyria has been thought to form the basis for the prevalent myths of vampires.
These diseases are rare, but there is evidence for hereditary porphyria in European royal families, and it may have been responsible for the madness of King George III as well as for the psychotic behavior of the painter Vincent van Gogh, misdiagnosed as a depressive schizophrenic.
Tabach demonstrated how, with one click, it is possible to identify essentially all the genes known to be associated with porphyria as well as other genes that, based on their phylogenetic profile, are very likely to be involved.
The bioinformatics methods he developed have formed the basis for the establishment of a company dealing with computational pharmaceutics that would identify new indications for existing therapeutic agents. This could dramatically decrease the time and expense required to bring a new drug to market, and facilitate the development of treatments for rare orphan diseases.
In the coming years, his Jerusalem laboratory intends to focus on the identification of genes that prevent aging and protect against cancer, by considering the genes of some extraordinary species of organisms with increased longevity and an almost complete resistance to cancer.