Children’s Hospital of Wisconsin and the Medical College of Wisconsin in Wauwatosa recently made news when a team of geneticists sequenced the partial DNA of a young boy suffering from a rare stomach disease, in the hopes that the sequencing would lead to a diagnosis.
Elizabeth Worthey, Ph.D. in the Bioinformatics Program in the Medical College’s Human and Molecular Genetics Center, along with a team of ten software developers custom-designed the DNA analyzing software for the case involving the little boy. The software has now been reconstructed and its third version will be released in June. Worthey is already using and plans to further develop the software, known as CarpeNovo, Latin for “seize the new,” for additional diagnostic testing as well as future clinical research.
“Up until we developed CarpeNovo, there was no real tool to analyze the variants detected in genome sequencing,” Worthey said. “The software allows us to enter all the variants and set filters and exclusions to narrow down the number of possible variants that might be the cause of any particular disease.”
According to Worthey, there are usually thousands of variants, or differences in comparison to what geneticists consider a healthy, normal human being, in any given sequencing.
“Some variants are expected. They are caused by genetic differences such as gender or race and others have been found to occur naturally without causing any serious harm to the patient,” Worthey said. “The CarpeNovo software allows us to use a variety of filters to eliminate variants with those familiar types of genetic differences or that have been seen before in medical history.”
In the case with the young boy who had a rare stomach disease, the sequencing revealed more than 16,000 variants, Worthey said.
Prior to the development of CarpeNovo, those variants would have been sifted through manually over a period of years, Worthey said.
“I actually did the calculations,” she said. “It would have taken us 1,000 12-hour days to manually get through those variants. That’s nearly three years, and that was time that little boy probably didn’t have.”
It only took about a month to sequence the boy’s DNA, and much of that time was spent analyzing while working on the tool simultaneously, Worthey said.
“One of my colleagues here at the Medical College of Wisconsin, Dr. David Bick, recently used the tool to make a genetic diagnosis in approximately four days,” she said.
Once the variants have been narrowed down, geneticists can more closely look at the remaining variants and determine which genes the variants occur on and determine whether or not it can be determined that a mutation in that particular spot is likely to cause damage to the way the body normally functions.
“If a variant occurs within a gene or in a particular part of the gene that codes for the protein and it ends up changing the way it acts or interacts with other proteins in the body they are more likely to be damaging,” Worthey said.
The CarpeNovo software utilizes information and data collected from research institutions around the world to accurately filter through variations, Worthey said.
Online databases of genetic variants and the complications or diseases they have been known to cause do exist. Many of those databases have been built into the back end of the CarpeNovo software.
CarpeNovo will select genes based on filters applied by the user and then link back to the online database where that evidence is located, Worthey said.
“Once the variants are narrowed down we still check many of them manually,” Worthey said. “It’s important to be as accurate as possible, but the software allows us to start where the problem most likely will be found instead of sifting through thousands of variants.”
The Medical College of Wisconsin received certification from the College of American Pathologists for version two of its CarpeNovo software and the Medical College is currently using the tool to analyze additional genome sequences, Worthey said.
“For right now, the patients need to have been seen at Children’s Hospital,” Worthey said. “We have a committee who helps determine that all other options have been exhausted and that genome sequencing is the next best option for the patient because it is quite costly and it can open doors for a lot of information.”
The Medical College is also in the process of developing a committee for working with adults in oncology as well as exploring options for collaboration and partnerships with other medical centers and laboratories, Worthey said.
