Dr. Christoph W. Sensen

Director, Visual Genomics Centre, Professor, Department of Biochemistry and Molecular Biology, Adjunct Professor, Department of Computer Science University of Calgary
Researcher of the month: 
Oct 2012

Visualizing the best of both worlds

At 10 years old, Christoph Sensen took his first biology class. After school, he told his architect father that he’d found his life’s calling. He wanted to be a biologist. His father laughed at what he believed was a passing dream, but Sensen’s determination turned that childhood desire into fact, not fiction.

Linking the promise of computer science with biotechnology and medical research is another of Sensen’s passions. At the University of Calgary (U of C), he has pioneered internationally renowned bioinformatic systems that perform genome analysis for molecular biologists worldwide.

He heads the Visual Genomics Centre, a high-tech wonder that makes it possible to see the inner workings of any organism, including the human body, in four dimensions (4D) – space plus time.

Working with collaborators Sun Microsystems and Fakespace Systems, he and his team of software programmers created the world’s first computer-automated virtual environment (CAVE®), a three-wall-plus-floor projection system that uses Java 3D™.

The CAVE shows active biological systems, including cells, tissues and entire organisms. Inside, scientists can view and interact with 4D representations of their work. Motion-sensor glasses help them to track their way through the CAVE – making its virtual environment seem almost as natural as the physical world.

Building a CAVE

When he came to Calgary in 2001, Sensen was told to pursue his bioinformatics research in the medical context. “I had a chance to set a whole new field in motion,” he explains.

He confronted the challenge of helping scientists to visualize genomics. “Understanding how DNA works is not two-dimensional. We cannot solve it on a laptop screen. We need a projection system that allows us to develop this concept in x, y, and z plus time.”

Sensen had seen demonstrations of a CAVE prototype at the Argonne National Laboratory, a non-profit science and research laboratory at the University of Chicago. It was expensive and not adaptable to other projects. Then, in 2001, he saw another version of this tool at Sun Microsystems, developed with Java 3D, an easy-to-use programming language.

But Sun Microsystems’ CAVE was not for sale. “I had to phone some high-ranking officials before I got it into my lab,” he admits. “That was the start. We had the hardware but nothing else.”

His team worked hard to program CAVE. He laughs as he recalls the night before its opening in Calgary on February 28, 2002. “We had no functioning CAVE until 4:00 a.m. in the morning, because some hardware components failed at the last minute. We were expecting 300 guests and about 40 cameras from television stations and Reuters at 10:00 a.m.

“That night, we didn’t sleep. We were soldering parts in the lab. To this day, on my desk, I have the final failed part to remind me never to launch a new project until we’ve tested everything for at least two weeks.”

Gene annotation takes flight

“There are two kinds of people in the world,” says Sensen. “Those who like mathematics and those who don’t.”

Molecular biologists often have the impression that they don’t need to study mathematics, he explains, so about 15 years ago, his team developed two software programs that work in tandem to help them to decode and depict their genomic research. Much of the work was funded by the National Research Council of Canada and later by Genome Canada through Genome Alberta.

Their first program, the Multipurpose Automated Genome Project Investigation Environment (MAGPIE), uses powerful, high-performance computers to generate gene annotations. It distills the results of multiple database searches for specific genes or gene sequences into a report that helps scientists to figure out the genes’ biological roles and origins.

“We compare a gene to all of the genes that exist in other genomes to find out whether or not it is similar,” Sensen explains. “If it is similar, then we can probably deduce its function.”

BLUEJAY enables researchers to show the world “exactly what your story and message is,” says Sensen. “We find it most useful to present biologists with a visual output that highlights their findings in an easy-to-understand way.”

For example, scientists can use BLUEJAY to highlight a specific set of interesting genes on a publication-ready graphic by removing or “greying out” other genes in that genome for display purposes.

“You can do this with many different views – from pie chart to high-resolution figure-based illustrations, text files and more. You can get exactly the view that you want to publish working within the one environment,” he says.

Sensen is proud of the fact that scientists don’t need a handbook for BLUEJAY. “Our end users (scientists) do not need to write scripts or input parameters. The pipelines are ready for them to use. Once they input the data and push the go button, they get a graphic output that they can use in publications or study reports.”

BLUEJAY runs on any laptop and is available for free at www.visualgenomics.ca. He estimates that researchers worldwide have downloaded over 8,000 copies.

The Centre also develops customized software for specific genomic projects. For example, OSPREY finds DNA primers – specific sections on a single strand of DNA, about 20 base pairs or less in length, where molecules bind to start a polymerase chain reaction (PCR). Scientists can use OSPREY to find a couple or more than 10,000 primers in any organism.

CAVEman: a 4D human body

Using CAVE technology, Sensen and his partners have created a high-resolution 4D digital atlas of human anatomy – the CAVEman – into which they can integrate disease-specific medical data.

The aim of the WEPA-funded Human Body Project was to create a visual map of diseases with a genetic link, such as cancer, Alzheimer’s and diabetes. To achieve this goal, Sensen and his U of C team partnered with Kasterstener Publications of Red Deer, AB, a company that develops anatomical teaching aids.

CAVEman’s virtual human body contains more than 3,000 objects, including skin, bones, organs, tissue and cells – with more complexity on the way. CAVEman will enable scientists to view disease processes over time and study how interventions, such as drugs, affect them.

For example, CAVEman has enabled scientists to see how bone porosity changes as we age. 

The collaboration began after a group of massage-therapy students from Red Deer visited the CAVE. They told Sensen that a school instructor had generated models of human bones with Autodesk® Maya®, the computer-animation program that created Toy Story and Jurassic Park.

“We said, fantastic, where’s the rest of it!” says Sensen. But bone modeling was as far as the Red Deer group had gone. He convinced them to submit a joint funding proposal to build an anatomically correct 3D human body, compatible with what medical students learn in anatomy texts. They received a grant to flesh out CAVEman from Genome Canada and Genome Alberta.

“You can see inside the body,” says Sensen. “You can see through the skin. You can see the heart and other organs. We can even make the skin or other objects disappear.”

He plans to integrate data from BRENDA, the world’s largest enzyme database, into CAVEman to create a unique tool for the study of enzyme distribution and activity over time in enzyme-related human diseases.

He is also working on a European Union proposal to develop a 4D human body model like CAVEman for systems biology experiments. The project would involve more than 100 European partners, including the University of Manchester, UK, and Max Planck Institute in Germany.

Finding a DNA signature of Mad Cow disease

In the molecular biology laboratory, Sensen is studying the possibility of using DNA fragments – circulating nucleic acids – in blood as biomarkers of chronic disease. Recently, he and his team completed a study on chronic wasting diseases in elk. They are now using that knowledge to find DNA markers of bovine spongiform encephalopathy (BSE) in cattle.

Sensen had doubts about the research. “Somebody told me, if we remove all of the cells in blood then sequence what’s left, we might find DNA markers of disease progress. I said that could never work,” he says.

“Out of curiosity, I told them that I would take on this task to prove them wrong. But when we got the results, it hadn't failed. There was some potential there! When we started this work, it was an obscure corner of science. Now, more than 200 papers per month with this sort of approach are published worldwide.”

Sensen and his team are searching for DNA markers that signal the host cow’s immune defense against BSE. This DNA signature must be easy to measure, and a detection test must be as accurate, highly specific, and rapid as a paternity test and inexpensive – less than $1.00 per unit, Sensen estimates, to be economically viable.

In future, Sensen hopes to look for the DNA signatures of chronic human diseases, such as cancer and diabetes.