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


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:

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 or

Lucky Tran | EurekAlert!

Further reports about: Biology CUMC drugs proteins

More articles from Health and Medicine:

nachricht Advanced analysis of brain structure shape may track progression to Alzheimer's disease
26.10.2016 | Massachusetts General Hospital

nachricht Indian roadside refuse fires produce toxic rainbow
26.10.2016 | Duke University

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: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

VDI presents International Bionic Award of the Schauenburg Foundation

26.10.2016 | Awards Funding

3-D-printed magnets

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>