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Clinical Laboratories and Pathology Groups

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Study may lead to repurposing existing drugs that are proven to be safe for the treatment of related diseases as the interactome becomes the subject of more research efforts

Researchers from multiple scientific institutions working together have begun using the protein interactome to understand what combination of unique biomarkers is a reliable indicator that a specific drug would benefit a patient. Armed with that knowledge, pharmaceutical companies plan to develop a drug that benefits individuals who have that collection of biomarkers/interactome.

Of course, once the drug exists, the next step is to develop a clinical laboratory test that looks for those biomarkers so that patients can be diagnosed and identified as candidates for the new drug treatment.

Microbiologists and clinical laboratory scientists engaged in “omic” studies—such as genomics, proteomics, metabolomics, metagenomics, phenomics, and transcriptomics—know that scientists are increasingly working to use ever-larger numbers of biomarkers to collectively identify if an individual patient would benefit from a specific drug. This ongoing research is at the heart of precision medicine treatments.

The researchers published their findings in the journal Nature Genetics, titled, “Network Expansion of Genetic Associations Defines a Pleiotropy Map of Human Cell Biology.”

“This work bridges many fields of biology, including statistical genetics, cell biology, and bioinformatics,” said Pedro Beltrão, PhD, Professor in the Department of Biology at ETH Zürich’s Institute of Molecular Systems Biology and former group leader at EMBL-EBI. Microbiologists and clinical laboratories engaged in “omic” studies will understand the significance of this study. (Photo copyright: Gulbenkian Science.)

Study Finds Biological Support for Repurposing Existing Drugs

The study, conducted by scientists at GlaxoSmithKline, Open Targets, and the European Molecular Biology Laboratory’s European Bioinformatics Institute (EMBL-EBI), focused on identifying protein interactomes that may advance the creation of new pharmaceuticals.

According to Genetics Engineering and Biotechnology News (GEN), “A protein interactome—the network of all possible protein interactions—constitutes an important intermediary step that could bridge the often difficult to cross chasm between genotype [an organism’s complete set of genetic material] and phenotype [an organism’s observable characteristics or traits], and is key in identifying drug targets.”

The scientists discovered more than 1,000 human traits from 21 therapeutic areas, GEN reported. Their process identified drug targets and genes linked to diseases because it pinpoints the shared basis of diseases utilizing a map of interactive human proteins.

The more defined the links are between genetic mechanisms, human traits, and diseases, the more likely their methods can help pharmaceutical companies prioritize those targets for new drugs, and for potentially repurposing existing FDA-approved drugs, the scientists noted.

The study accessed multiple databases including Reactome, Signor, and the EMBL-EBI’s IntAct. The researchers used genome-wide association studies (GWAS) to identify interacting protein groups that were genetically linked.

“The interactome identified some known associations, such as cardiovascular diseases and lipoprotein or cholesterol measurements,” Inigo Barrio Hernandez, PhD, a postdoctoral fellow at Open Targets and EMBL-EBI, told GEN. “But we also found some unexpected associations. For example, the interactome highlighted three protein clusters shared by ten respiratory and skin immune-related diseases. This is hugely exciting because we now have some biological support to repurpose existing drugs that are proven to be safe to treat related diseases.”

The researchers also identified 73 protein clusters linked to more than one trait or disease. This is known as pleiotropy. Pleiotropic relationships are goldmines to drug companies because they show how a therapy for one disease could effectively treat another, and in addition, it provides insight on targets that could trigger side effects, GEN reported.

What Comes Next?

Pedro Beltrão, PhD—Biology Professor at ETH Zürich’s Institute of Molecular Systems Biology and former group leader at EMBL-EBI—noted the significance of this collaborative study. “It brought together groups from across Open Targets and EMBL-EBI and highlights the value of collaborations across disciplines,” he told GEN.

The study researchers plan to continue identifying, mapping, and utilizing their findings for drug development.

“This is an exciting showcase … that has generated an array of new insights for novel target discovery as well as drug repurposing, and informs our understanding of the connection between rare and common diseases through shared biological processes,” Ellen McDonagh, PhD, Director of Informatics Science at Open Targets, told GEN. “This is now being developed further to provide tissue and cell-type specific networks to help further prioritize targets for disease treatment.”

The term “interactome” was coined in 1999, but many microbiologists and clinical laboratory scientists may not be familiar with it. Considering the possibility of new drug therapies based on these newly discovered biomarkers—and the medical laboratory tests that will be needed to identify compatible patients—it’s a good idea to stay aware that protein interactome exists.

Researchers are working to identify the protein interactome, map it, and use it—both in drug discovery and development—as well as in clinical laboratory testing. More research and study is needed, so a medical lab test that advances patient care is a ways off. But the research is worth following.

—Kristin Althea O’Connor

Related Information:

Protein Interactome Offers Key Resource for Drug Discovery and Repurposing

Network Expansion of Genetic Associations Defines a Pleiotropy Map of Human Cell Biology

New Research Challenges Long-Held Theory about Causes of Alzheimer’s Disease, Creating the Possibility of Useful New Biomarkers for Clinical Laboratory Tests