Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Computational Process Zeroes in on Top Genetic Cancer Suspects

03.09.2009
Johns Hopkins engineers have devised innovative computer software that can sift through hundreds of genetic mutations and highlight the DNA changes that are most likely to promote cancer.

The goal is to provide critical help to researchers who are poring over numerous newly discovered gene mutations, many of which are harmless or have no connection to cancer. According to its inventors, the new software will enable these scientists to focus more of their attention on the mutations most likely to trigger tumors.

A description of the method and details of a test using it on brain cancer DNA were published in the August 15 issue of the journal Cancer Research.

The new process focuses on missense mutations, meaning protein sequences that each possess a single tiny variation from the normal pattern. A small percentage of these genetic errors can reduce the activity of proteins that usually suppress tumors or hyperactivate proteins that make it easier for tumors to grow, thereby allowing cancer to develop and spread. But finding these genetic offenders can be difficult.

“It’s very expensive and time-consuming to test a huge number of gene mutations, trying to find the few that have a solid link to cancer,” said Rachel Karchin, an assistant professor of biomedical engineering who supervised the development of the computational sorting approach. “Our new screening system should dramatically speed up efforts to identify genetic cancer risk factors and help find new targets for cancer-fighting medications.”

The new computational method is called CHASM, short for Cancer-specific High-throughput Annotation of Somatic Mutations.

Developing this system required a partnership of researchers from diverse disciplines. Karchin and doctoral student Hannah Carter drew on their skills as members of the university's Institute for Computational Medicine, which uses powerful information management and computing technologies to address important health problems, and collaborated with leading Johns Hopkins cancer and biostatistics experts from the university’s School of Medicine, its Bloomberg School of Public Health and the Johns Hopkins Kimmel Cancer Center.

The team first narrowed the field of about 600 potential brain cancer culprits using a computational method that would sort these mutations into “drivers” and “passengers.” Driver mutations are those that initiate or promote the growth of tumors. Passenger mutations are those that are present when a tumor forms but appear to play no role in its formation or growth. In other words, the passenger mutations are only along for the ride.

To prepare for the sorting, the researchers used a machine-learning technique in which about 50 characteristics or properties associated with cancer-causing mutations were given numerical values and programmed into the system. Karchin and Carter then employed a math technique called a Random Forest classifier to help separate and rank the drivers and the passengers. In this step, 500 computational “decision trees” considered each mutation to decide whether it possessed the key characteristics associated with promoting cancer. Eventually, each “tree” cast a vote: Was the gene a driver or a passenger?

“It’s a little like the children’s game of ‘Guess Who,’ where you ask a series of yes or no questions to eliminate certain people until you narrow it down to a few remaining suspects,” said Carter, who earned her undergraduate and master’s degrees at the University of Louisville and served as lead author of the Cancer Research paper. “In this case, the decision trees asked questions to figure out which mutations were most likely to be implicated in cancer.”

The election results—such as how many driver votes a mutation received—were used to produce a ranking. The genetic errors that collected the most driver votes wound up at the top of the list. The ones with the most passenger votes were placed near the bottom. With a list like this in hand, the software developers said, cancer researchers can direct more of their time and energy to the mutations at the top of the rankings.

Karchin and Carter plan to post their system on the Web and will allow researchers worldwide to use it freely to prioritize their studies. Because different genetic characteristics are associated with different types of cancers, they said the method can easily be adapted to rank the mutations that may be linked to different forms of the disease, such as breast cancer or lung cancer.

In addition to Karchin and Carter, the Johns Hopkins co-authors of the Cancer Research paper were Sining Chen, Leyla Isik, Svitlana Tyekucheva, Victor E. Velculescu, Kenneth W. Kinzler and Bert Vogelstein.

Funding for the research was provided by the National Cancer Institute, the Susan G. Komen Foundation, the Virginia and D. K. Ludwig Fund for Cancer Research and the National Institutes of Health.

Color images of the researchers available; Contact Phil Sneiderman.

Related links:
Rachel Karchin’s Lab Page: http://karchinlab.org/
Department of Biomedical Engineering: http://www.bme.jhu.edu/
Johns Hopkins Institute for Computational Medicine: http://www.icm.jhu.edu/
Johns Hopkins Kimmel Cancer Center: http://www.hopkinskimmelcancercenter.org/

Phil Sneiderman | Newswise Science News
Further information:
http://www.jhu.edu

More articles from Information Technology:

nachricht Construction of practical quantum computers radically simplified
05.12.2016 | University of Sussex

nachricht UT professor develops algorithm to improve online mapping of disaster areas
29.11.2016 | University of Tennessee at Knoxville

All articles from Information Technology >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>