Our Young Investigator series allows us to acknowledge rising scientists in the forensic field. We hope that they inspire you with their story, as they are our future!
As a part of this series, we have Michelle Peck, DNA Validation and Development Coordinator at the International Commission on Missing Persons, The Hague, Netherlands. Her focus is on Massively Parallel Sequencing (MPS) methods for missing persons identification. Let’s follow her story!
Tell us about your background and how you became interested in forensic science?
From a very young age, I wanted to be a forensic scientist. I remember visiting the Maryland Science Center as a kid and seeing a CSI exhibit – I was immediately fascinated! Learning more about the field, I was drawn to the fact that there is an amazing application of science that has a direct impact on individuals and society as a whole. After getting my undergraduate degree in Molecular Biology, I attended George Washington University for my master’s degree. I had great experiences there in learning how instrumental research is to advancing the field. I then worked at the Armed Forces DNA Identification Laboratory for 5 years in the Emerging Technologies department, gaining experience in the application of MPS methods to forensic casework. I am currently at the ICMP working on research and validation of MPS methods applied to missing persons.
Can you provide a summary of the project you are working on?
We are working on developing a very large MPS SNP panel for identification of the missing. Massively Parallel Sequencing makes it possible to sequence hundreds to thousands of SNPs simultaneously, enabling identification of the missing from more distant relatives. Furthermore, being able to utilize SNPs as the marker of interest is more suited to degraded DNA as the target can be very small. Our panel design, developed in collaboration with Chris Phillips at the University of Santiago de Compostela and Andreas Tillmar of Linkoping University, consists of over 1400 SNPs and 45 microhaplotypes, which were selected for high heterozygosity. We are utilizing QIAGEN’s QIAseq library preparation method, which uses the novel features of single primer extension and unique molecular indices (UMIs). Currently, we are evaluating the performance of the SNPs and optimizing the library preparation steps to handle low quantity inputs.
Please describe a typical day for you in the lab.
A lot of my time is spent using QIAGEN’s Biomedical Genomics Workbench to sift through the vast amount of data that is produced with this method. Different tasks include optimizing parameters in the analysis workflow and evaluating the sequencing metrics of the SNPs to establish what is reliable data. When I am in the lab, I will likely be testing different variables in the library preparation method. This usually involves performing many bead purification steps. It is always exciting when I get to start a sequencing run knowing there will be lots of data to analyze once it’s complete!
What do you find most interesting about your project? Have you seen any surprising results?
It is very interesting to see how the library preparation method directly impacts the sequencing reads. When adapters are added and how long those adapters are influences how much usable sequence data is produced. This is critical to think about in designing primers and the library preparation strategy. Purification steps are also critical to optimize to ensure that the DNA fragments are of the appropriate size. It is intriguing to see how changing these steps have an impact on the sequencing reads and can ultimately lead to higher coverage of the targets of interest.
What are the benefits of your research?
This SNP panel has the potential to lead to identifications of the missing that are not possible with the current technology. In cases where there are too few family reference samples and/or they are more distant relationships, STRs do not lead to enough statistical evidence to find a match. This is often the case with older missing persons events where first degree relatives may no longer be living or when it is harder to find family members, which will likely be the case with missing migrants. Furthermore, when bone samples are heavily degraded, the STR profile may fail or only generate a partial profile, again leading to low statistics. The smaller targets that are needed to generate SNP data makes it feasible to generate profiles with these samples. Again, potentially leading to identifications that would not be possible otherwise.
What are the major challenges you face with regards to the NGS method and how do you overcome them?
One of the major challenges with MPS methods is adapting them to forensic samples, in which low quantity samples are the norm. Optimizing the procedure to accommodate these low inputs, while ensuring the reliability and reproducibility of the results is critical. Another challenge to consider as MPS methods make typing new markers more feasible, is the availability of known samples for the targets of interest to check for concordance. We have been utilizing samples from the Genome in a Bottle Consortium that are characterized for the whole genome to ensure our data is reliable. Additionally, sequencing on different sequencing platforms helps account for sequencing artifacts. Both these challenges highlight the necessity of extensive testing and validation before bringing a new method online.
Which QIAGEN products do you use and what do you like about the products?
QIAGEN products are utilized throughout this MPS SNP method: QIAseq Library Prep Kit, the QIAxcel Advance System for quantification, the GeneReader Platform, and the Biomedical Genomics Workbench for analysis. The QIAseq method is robust and utilizes the novel technology of unique molecular indices, which helps minimize PCR and sequencing error by tracing sequences reads back to the original molecule. This may be very beneficial in case of low quantity samples to help account for low template stochastic effects. The Biomedical Genomics Workbench provides many tools to analyze the data with helpful reports and output tables. Being able to visualize the sequence reads in the software is also very helpful in putting the data into context. Beyond my work with MPS, QIAGEN DNA purification products are extensively used in ICMP’s high-throughput testing of degraded skeletal remains.
Outside of forensic science, what are your hobbies?
I love to play sports (especially soccer!), to travel and explore, and to serve at my church.
You can learn more about Michelle’s work from her conference presentation slides presented at the 7th QIAGEN Investigator Forum.