Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

An innovative algorithm is helping scientists decipher how drugs work inside the body

24.07.2015

Researchers at Columbia University Medical Center (CUMC) have developed a computer algorithm that is helping scientists see how drugs produce pharmacological effects inside the body. The study, published in the journal Cell, could help researchers create drugs that are more efficient and less prone to side effects, suggest ways to regulate a drug's activity, and identify novel therapeutic uses for new and existing compounds.

"For the first time we can perform a genome-wide search to identify the entire set of proteins that play a role in a drug's activity," says study co-author Dr. Andrea Califano, the Clyde and Helen Wu Professor of Chemical Systems Biology and chair of the department of Systems Biology at CUMC.


By analyzing drug-induced changes in disease-specific patterns of gene expression, a new algorithm called DeMAND identifies the genes involved in implementing a drug's effects. The method could help predict undesirable off-target interactions, suggest ways of regulating a drug's activity, and identify novel therapeutic uses for FDA-approved drugs, three critical challenges in drug development. GIF version here: http://newsroom.cumc.columbia.edu/?p=34484

Credit: Califano lab/Columbia University Medical Center

Scientists design drugs to pinpoint molecular targets in the cell. However, when a drug enters the human body, it becomes part of an incredibly complex system, and can interact with other molecules in ways that are hard to predict. This unanticipated cross-talk causes side effects and stops many promising drug candidates from being used in clinical care. Unfortunately, current experimental methods don't allow scientists to identify the full repertoire of proteins that are affected by a drug.

Members of Dr. Califano's lab have devised a new approach called DeMAND.

... more about:
»Biology »CUMC »drugs »proteins

(Detecting Mechanism of Action by Network Dysregulation) to characterize a drug's effects more precisely. The method involves creating a computational model of the network of protein interactions that occur in a diseased cell. Experiments are then performed to track gene expression changes in diseased cells as they are exposed to a drug of interest. The DeMAND algorithm combines data from the model with data from the experiments to identify the complement of proteins most affected by the drug.

DeMAND improves on more labor intensive and less efficient methods, which are only capable of identifying targets to which a compound binds most strongly. This provides a more comprehensive picture, because DeMAND identifies many molecules that are affected in addition to the drug's direct target.

So far, DeMAND's predictions are proving to be accurate when tested with follow-up experiments. The researchers report that when they exposed human diffuse B-cell lymphoma cells to a panel of drugs, the algorithm identified 70% of previously documented targets. "The accuracy of the method has been the most surprising result," says Dr. Califano.

The algorithm makes it possible to identify a variety of compounds that cause similar pharmacological outcomes. Using DeMAND, the researchers showed that a similar subset of proteins is affected by the unrelated drugs sulfasalazine and altretamine. Altretamine is currently used to treat ovarian cancer, but these results suggest that, like sulfasalazine, it could be used for bowel inflammation or rheumatoid arthritis too.

Co-senior author Mukesh Bansal sees great potential in this approach, saying, "DeMAND could accelerate the drug discovery process and reduce the cost of drug development by unraveling how new compounds work in the body. Our findings on altretamine also show that it can determine novel therapeutic applications for existing FDA-approved drugs."

###

The Cell paper is titled, "Elucidating Compound Mechanism of Action by Network Perturbation Analysis." The list of authors is: Andrea Califano, Jung Hoon Woo, Yishai Shimoni, Wan Seok Yang, Prem Subramaniam, Archana Iyer, Paola Nicoletti, María Rodríguez Martínez, Gonzalo López, Ronald Realubit, Charles Karan, Brent R. Stockwell, Mukesh Bansal (all at CUMC), and Michela Mattioli, (Fondazione Istituto Italiano di Tecnologia).

This work was supported by grants from the National Institutes of Health (5U01CA168426, 1U01CA164184-02, 3U01HL111566-02, 5U54CA121852-08, 5R01CA097061, R01CA161061), New York Stem Cell Science (C026715) and the Howard Hughes Medical Institute.

The authors declare no financial or other conflicts of interest.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast.

For more information, visit cumc.columbia.edu or columbiadoctors.org.

Lucky Tran | EurekAlert!

Further reports about: Biology CUMC drugs proteins

More articles from Health and Medicine:

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

nachricht The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>