Kelly Nudelman and Tae-Hwi Schwantes-An discuss the importance of sample identification and quality control at the Indiana University Genetics Biobank

While troubleshooting a temporary roadblock in one of her own research studies, Kelly Nudelman, PhD, Assistant Research Professor at the Indiana University School of Medicine, discovered a previously unrealized passion for helping other scientists solve problems and ensure the integrity of their research with DNA fingerprinting.

“I had reached an impasse in my study and wondered if the problems I was encountering might be attributed to my research samples. While assessing what was going on, I determined the issue didn’t have to do with the samples I obtained from the biorepository,” she said. “It was a simple calibration issue with some of the instruments I was using. I was able to resume my research, and also realized my fascination with the troubleshooting process.”

Recognizing Nudelman’s talent, Tatiana Foroud, PhD, Scientific Director of the Indiana University Genetics Biobank (IUGB), a notable biorepository run by staff and faculty in the IU School of Medicine, recruited her to join the team.

The IUGB was established in 1990 as a national central repository for research on dementia, funded by the National Institutes of Health, and has since expanded to include a broad range of sample collections with more than 1 million tissue specimens catalogued. The biospecimen types span many indications, including Huntington’s, Parkinson’s and Alzheimer’s diseases. The IUGB’s largest collection is comprised of DNA samples, which are obtained from blood and tissue. More than 240,000 DNA aliquots are distributed annually, supporting hundreds of studies varying in size and scope.

Tae-Hwi (Linus) Schwantes-An, an Assistant Research Professor working alongside Nudelman at the IUGB, has a similar mission. “While my primary research is in liver and kidney disease, what’s really exciting about DNA fingerprinting is working with the people in the lab and collaborating to solve problems.”

Schwantes-An provides scientific support to the biobank, including managing the technical aspects of the DNA fingerprinting process. “This work gives me that additional level of awareness when I look at my own studies. I'm able to ask better questions, and answer questions better.”

Just over one year ago, IUGB transitioned to the DNA fingerprinting methodology enabled by Fluidigm microfluidics technology and systems for genomic analysis, specifically Juno™ and Biomark™ HD. The biobank has a custom-designed panel of 96 SNPs, and it incorporates this panel into a workflow that allows the biobank to simultaneously confirm sample identity and conduct quality checks at key points in the lab’s workstream. Those include before sample accession and again before distribution of samples to requesting researchers.

“One of our goals is to ensure that all of our samples have been quality-controlled to the highest standard,” Nudelman said. “Using DNA fingerprinting to assess samples prior to accession and distribution can save time and resources. Researchers who receive samples from the biorepository need to have confidence that the samples they receive have been correctly identified from the sample source. Additionally, researchers need to have confidence that the samples will yield interpretable data from their planned downstream analyses.”

Because the biobank distributes DNA more than any other type of sample, the team is always looking to improve its distribution and stable storage processes. The Fluidigm workflow was chosen because of its scalability and cost-efficiency and the small quantity of DNA needed to test samples.

“We found that many alternative workflows are either high-throughput/high-cost or low-throughput/low-cost,” said Schwantes-An. “What makes the Fluidigm microfluidics-based workflow unique is that it is high-throughput at a cost that is scalable to our process. It saves our customers and our lab time and resources.”

Ensuring quality control with the Fluidigm DNA fingerprinting workflow

In implementing the Fluidigm microfluidics-based workflow for DNA fingerprinting, Nudelman and Schwantes-An employ a custom-designed SNP panel developed by the IUGB to generate a molecular fingerprint for each sample. The specific assays chosen for the panel enable the team to produce not only a DNA fingerprint for each sample, but also to verify other aspects of sample quality, such as sample swaps, contamination, degradation or discordance in reported versus genetic sex.

The biobank’s customer requests for distribution can vary from two samples to thousands of samples and encompass researchers across segments from academia to clinical research. Bringing DNA fingerprinting in-house enabled the biobank to conduct more streamlined testing before accession and distribution and to better identify and understand potential issues, such as a swapped sample, degraded sample or non-concordance between accession and pre-distribution sample tests. As a result, the biobank can move faster and produce more informative and higher-quality data.

“If a scientist is using a poor-quality sample, the mistake can amplify and cause a cascade of issues as the study moves forward,” Schwantes-An said. “DNA fingerprinting allows us to detect events that might otherwise lead to erroneous results. It helps us spot potential issues before we send samples to the requesting researcher.”

Future implications for DNA fingerprinting

In addition to using the Fluidigm microfluidics workflow, the team at IUGB has been able to collaborate with experts at Fluidigm to design assays for additional genetic variants of interest.

“For example, as the field of neurodegenerative disease grows, new targets of interest will be identified,” Schwantes-An explained. “Being able to customize the assay allows us to adapt to how the field is changing, and this is something we can do using the Fluidigm workflow. Let’s say, for example, a new variant is discovered, and everyone wants to know the status for that particular variant in her or his sample. We’ll be able to easily make a modification to our panel, adding the new variant quickly.”

Nudelman added that they are also interested in adapting this technology to other types of samples. “We feel there's a lot of potential that we could leverage for other things that we're doing,” she said. “For example, our DNA fingerprinting workflow has the potential to be leveraged through our induced pluripotent stem cell workflow.”

For Nudelman, working at the biobank has provided a greater connection to the larger research community.

“Working at the biobank, I get a bird’s-eye view of the research happening in the community,” she said. “Our samples are central to so many research programs, and it’s an amazing feeling to know you’re touching so many people through this process—making things run smoother and ensuring better-quality data.”

Schwantes-An also enjoys working with the biobank to help other investigators, and to fulfill the wishes of individuals who donate their personal samples for future research.

“We’re working together, trying to meet one goal,” said Schwantes-An. “We want to make sure we send out the best-quality samples to the investigators. Oftentimes, patients donate their samples because they're altruistic. It is their desire to help advance clinical research. I feel a sense of duty to make sure that their generosity doesn’t go to waste. Using Fluidigm’s microfluidics workflow for DNA fingerprinting is allowing us to fulfill what these patients wanted, which is sharing their samples for the advancement of medical research.”