SBP researchers combine publicly available cancer databases to identify new genes associated with cancer
In a collaborative study led by Sanford Burnham Prebys Medical Discovery Institute (SBP), researchers have combined two publicly available 'omics' databases to create a new catalogue of 'cancer drivers'. Cancer drivers are genes that when altered, are responsible for cancer progression.
The researchers used cancer mutation and protein structure databases to identify mutations in patient tumors that alter normal protein-protein interaction (PPI) interfaces. The study, published today in PLoS Computational Biology, identified more than 100 novel cancer driver genes and helps explain how tumors driven by the same gene may lead to different patient outcomes.
"This is the first time that three-dimensional protein features, such as PPIs, have been used to identify driver genes across large cancer datasets," said lead author Eduard Porta-Pardo, Ph.D., a postdoctoral fellow at SBP.
"We found 71 interfaces in proteins previously unrecognized as cancer drivers, representing potential new cancer predictive markers and/or drug targets. Our analysis also identified several driver interfaces in known cancer genes, such as TP53, HRAS, PI3KCA and EGFR, proving that our method can find relevant cancer driver genes and that alterations in protein interfaces are a common pathogenic mechanism of cancer."
Cancer is caused by the accumulation of mutations to DNA. Until now, scientists have focused on finding alterations in individual genes and cell pathways that can lead to cancer. But the recent push by the National Institutes of Health (NIH) to encourage data sharing has led to an era of unprecedented ability to systematically analyze large scale genomic, clinical, and molecular data to better explain and predict patient outcomes, as well as finding new drug targets to prevent, treat, and potentially cure cancer.
"For this study we used an extended version of e-Driver, our proprietary computational method of identifying protein regions that drive cancer. We integrated tumor data from almost 6,000 patients in The Cancer Genome Atlas (TCGA) with more than 18,000 three-dimensional protein structures from the Protein Data Bank (PDB)," said Adam Godzik, Ph.D, director of the Bioinformatics and Structural Biology Program at SBP. "The algorithm analyzes whether structural alterations of PPI interfaces are enriched in cancer mutations, and can therefore identify candidate driver genes."
"Genes are not monolithic black boxes. They have different regions that code for distinct protein domains that are usually responsible for different functions. It's possible that a given protein only acts as a cancer driver when a specific region of the protein is mutated," Godzik explained. "Our method helps identify novel cancer driver genes and propose molecular hypotheses to explain how tumors apparently driven by the same gene have different behaviors, including patient outcomes."
"Interestingly, we identified some potential cancer drivers that are involved in the immune system. With the growing appreciation of the importance of the immune system in cancer progression, the immunity genes we identified in this study provide new insight regarding which interactions may be most affected," Godzik added.
The study was performed in collaboration with the European Bioinformatics Institute (UK), Centro de Investigación Principe Felipe (Spain), and CIBER de Enfermedades Raras (Spain).
This study was supported by SPB funds and NIH grant GM101457.
About Sanford Burnham Prebys Medical Discovery Institute
Sanford Burnham Prebys Medical Discovery Institute (SBP) is an independent nonprofit research organization that blends cutting-edge fundamental research with robust drug discovery to address unmet clinical needs in the areas of cancer, neuroscience, immunity, and metabolic disorders. The Institute invests in talent, technology, and partnerships to accelerate the translation of laboratory discoveries that will have the greatest impact on patients. Recognized for its world-class NCI-designated Cancer Center and the Conrad Prebys Center for Chemical Genomics, SBP employs more than 1,100 scientists and staff in San Diego (La Jolla), Calif., and Orlando (Lake Nona), Fla. For more information, visit us at SBPdiscovery.org. The Institute can also be found on Facebook at facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.
Susan Gammon | EurekAlert!
Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
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...
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...
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...
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...
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...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences