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
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