Lab Matters Winter 2020 - Page 26

NEWBORN SCREENING The Impact of Bioinformaticians in Newborn Screening Systems By Samantha Marcellus, MPH, newborn screening bioinformatics and data analytics fellow, Texas Department of State Health Services; Charles Roberts, MS, newborn screening bioinformatics and data analytics fellow, Wisconsin State Laboratory of Hygiene; and Hiral Desai, MS, specialist, Bioinformatics, Newborn Screening and Genetics. Since the completion of the human genome project in 2001, there has been a surge in pinpointing genetic variants as drivers of enigmatic disorders. This capability is integral to advancing public health newborn screening (NBS), where timely detection of pathogenic gene mutations during routine NBS can result in early treatment and favorable health outcomes. The emergence of new genomic knowledge through next- generation sequencing (NGS) parallels the evolution of the public health sector to assimilate a broad spectrum of validated screening technologies, assays, follow-up procedures and specialists to positively influence the lives of newborns across all populations. Combining genomic information and therapy has also necessitated the involvement of bioinformaticians in NBS public health systems to analyze complex genomic data that may be critical for life- changing outcomes. Addressing the Paradigm Shift in Texas Many public health laboratory NBS programs have either implemented or forecasted the adoption of high- throughput sequencing methods for relevant disorders contingent on various social, ethical and legal questions impacting neonates. With the assistance of Samantha Marcellus, the Texas Department of State Health Services is building bioinformatics infrastructure from the ground up for the newborn screening and infectious diseases programs. This involves leveraging hardware components to sustain Illumina sequencing machines and custom software without creating bottlenecks or utilizing computational resources that are necessary for other assays. The development of bioinformatics infrastructure is essential for a targeted 24 LAB MATTERS Winter 2020 NBS Bioinformatics Fellow Samantha Marcellus NBS Bioinformatics Fellow Charles Roberts 39-gene panel for severe combined immunodeficiency (SCID) analysis to foster early detection and treatment for affected infants. With the advent of bioinformatics hardware, Marcellus will be a key bioinformatician in researching pipelines and tools for parsing raw NGS data for SCID and other relevant disorders that require genomic analysis to accurately report genetic variants to health care providers. a bioinformatics process to curate the quality of variant calls from many variants known to exist within the Plain population. This project is a perfect example of how bioinformatics tools can be used in newborn screening and personalized medicine. Roberts also is using data-driven approaches to automate several time consuming NBS processes to allow more time for integrating new disorders as they are added to the Recommended Uniform Screening Panel (RUSP). Implementing New Technology in Wisconsin In most laboratories, bioinformatics- based interrogations are incorporated primarily into the laboratory algorithm as confirmatory second- or third-tier NBS tests for targeted conditions. Mass spectrometry remains the gold standard because it can rapidly measure many metabolites in different biological specimens in a sensitive and specific manner using multiplexing. In 2020, bioinformaticians have become essential to interpreting newborn screening results and their value will only increase as more complex disorders are added to the RUSP. To respond to the paradigm shift in next-generation sequencing, public health programs must train, hire and develop these critical members of the newborn screening community. n The Wisconsin State Laboratory of Hygiene was one of the first laboratories to implement NGS technology for both testing and bioinformatics. Its fellow, Charles Roberts is currently engaged in developing an NBS NGS panel specifically for the Amish Plain Community as a first-tier test. He has been developing PublicHealthLabs @APHL