Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Method of the future uses single-cell imaging to identify gene interactions

09.02.2010
Cellular imaging offers a wealth of data about how cells respond to stimuli, but harnessing this technique to study biological systems is a daunting challenge.

In a study published online in Genome Research, researchers have developed a novel method of interpreting data from single-cell images to identify genetic interactions within biological networks, offering a glimpse into the future of high-throughput cell imaging analysis.

For years, scientists have been peering through a microscope at cells as they change appearance in response to different treatments, yet data collection is arduous, largely conducted qualitatively by eye. However, recent technological advances have led to the development of high-throughput image screening methods that can produce extensive datasets of hundreds of different morphological features.

With the ability to collect large imaging datasets, researchers from MIT and Harvard Medical School recognized an opportunity to explore the cellular networks that regulate cell morphology. "These images are an enormous source of data that is only beginning to be tapped," said MIT researcher Bonnie Berger, senior author of the work published today. "We realized we had enough data to go beyond classification and start to understand the mechanism behind the differences in shape."

To meet the challenge of interpreting cell image data, Berger and MIT graduate student Oaz Nir developed a novel computational model to identify genetic interactions using high-dimensional morphological data. Integrating prerequisite knowledge of a pathway, their model maps potential interactions within a network by looking for similar morphological features upon genetic perturbation.

The group demonstrated the method by analyzing the Rho-signaling network in fruit flies, a network that regulates cell adhesion and motility in eukaryotic organisms. In collaboration with Chris Bakal and Norbert Perrimon at Harvard Medical School, they "knocked-down" components of the Rho-signaling network using RNA interference and then imaged thousands of fly cells, gathering measurements of cell perimeter, nuclear area, and more than 150 other morphological features for each cell. The data was then passed through the computational framework to produce a set of high-confidence interactions, supported by confirmation of previously known interactions.

The group found that by making combinatorial knockdowns of Rho network components, their computational method was able to accurately infer Rho-signaling network interactions more precisely than when using only data from single knockdowns. Berger noted that this finding highlights the importance of combinatorial experiments for inferring complex networks, necessary to overcome natural redundancy in signaling pathways. As perturbation of the Rho pathway in humans has been implicated in cancer and other diseases, the authors believe that these predicted interactions will be excellent candidates for future study.

Berger expects that in combination with other sources of data, imaging as a new source of high-throughput data should appreciably increase the accuracy of known signaling networks. "This work provides a glimpse into the future," added Berger, "where looking under the microscope manually at cells one-by-one is replaced with automated high-throughput processing of many cellular images."

Scientists from the Massachusetts Institute of Technology (Cambridge, MA) and Harvard Medical School (Boston, MA) contributed to this study.

This work was supported by the Department of Energy, the Leukemia and Lymphoma Society, the National Institutes of Health, and the Howard Hughes Medical Institute.

Media contacts: The authors are available for more information by contacting Jennifer Hirsch at the MIT News Office (jfhirsch@mit.edu; +1-617-253-1682).

Interested reporters may obtain copies of the manuscript from Peggy Calicchia, Editorial Secretary, Genome Research (calicchi@cshl.edu; +1-516-422-4012).

About the article: The manuscript will be published online ahead of print on February 9, 2010. Its full citation is as follows: Nir O, Bakal C, Perrimon N, Berger B. Inference of RhoGAP/GTPase regulation using single-cell morphological data from a combinatorial RNAi screen. Genome Res doi:10.1101/gr.100248.109.

About Genome Research:

Launched in 1995, Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.

About Cold Spring Harbor Laboratory Press:

Cold Spring Harbor Laboratory is a private, nonprofit institution in New York that conducts research in cancer and other life sciences and has a variety of educational programs. Its Press, originating in 1933, is the largest of the Laboratory's five education divisions and is a publisher of books, journals, and electronic media for scientists, students, and the general public.

Genome Research issues press releases to highlight significant research studies that are published in the journal.

Peggy Calicchia | EurekAlert!
Further information:
http://www.cshl.edu
http://www.genome.org

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>