Suggesting genes’ friends, facebook-style: New method reveals genes’ combined effects
Scientists at the European Molecular Biology Laboratory (EMBL) and the German Cancer Research Centre (DKFZ), both in Heidelberg, Germany, have developed a new method that uncovers the combined effects of genes. Published online today in Nature Methods, it helps understand how different genes can amplify, cancel out or mask each others’ effects, and enables scientists to suggest genes that interfere with each other in much the same manner that facebook suggests friends.
To understand the connections between genetic make-up and traits like disease susceptibility, scientists have been turning to genome-wide association studies, in which they compare genetic variants of people with a particular disease to those of healthy people. Such studies have linked many genes to diseases, but these links were often weak and not clear-cut, possibly because individual genes often do not act alone. The effects of a particular gene can depend on what other genes a person carries, and the new method developed by the teams of Wolfgang Huber at EMBL and Michael Boutros at DKFZ enables scientists to uncover and measure those combined effects.
The scientists took a set of genes that are important for cell signalling and, using a technique called RNA interference, silenced those genes two at a time, and compared the effect to what happens when you silence only one or the other member of each pair. In so doing, they were able to identify a new component in a cell-signalling process known as the Ras pathway, which is involved in cellular proliferation, and is known to go awry in tumour cells.
If two people have many friends in common on facebook, the odds are that those two people know each other – even if they themselves are not facebook friends. Similarly, genes that have similar genetic interaction profiles are likely to influence each other’s effects, and Huber, Boutros and colleagues can now suggest such ‘friends’ – i.e. genes that are likely to affect the same cellular processes. In the long run, this could help predict patient outcomes and adapt treatments for diseases such as cancer.
This project was supported by the CellNetworks Cluster, a novel institution at Heidelberg University supported by the Excellence Initiative (www.cellnetworks.uni-hd.de).
Horn, T., Sandmann, T., Fischer, B., Axelsson, E., Huber, W. & Boutros, M. Mapping of Signalling Networks through Synthetic Genetic Interaction Analysis by RNAi. Nature Methods, Advance Online Publication 6 March 2011. DOI: 10.1038/nmeth.1581.
A picture for this press release is available at:
Picture caption: By silencing genes two at a time in cells like these, the scientists can analyse the genes’ combined effects. In this microscopy image of human cells, nuclei are shown in red, cell membranes in green, and the cellular scaffolding in blue.
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 2,500 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.