Lab Matters Summer 2016 | Page 12

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The Wisconsin Newborn Screening Next Generation Sequencing Team. Front row( from l to r:) Mei Wang Baker, MD, FACMG, Marie Adams, Anne Atkins. Back row( from l to r:) Joshua Hyman, PhD, Michael Cogley, Gregory Kopish, Sean Mochal. Not pictured: Dr. Derek Pavelec

Despite its many pluses, NGS is not without challenges. Perhaps the biggest of these pertain to staffing and data analysis, two sides of the same coin.

Myers said,“ It takes highly skilled people to produce quality WGS results. Now you really do need people who are good with data and good with numbers. It’ s a personnel issue.”

While CDC has developed its own analysis pipelines that PHLs can use, the agency is also working with APHL to develop a cloud-based pipeline that can be accessed through the APHL Informatics Messaging Service Platform. The hope is, said Boxrud, that PHLs“ can have control over the analysis. CDC won’ t have to be the gatekeeper, but it can get the information it needs.”

Other challenges have to do with targeting the still-pricey technology to the most cost-effective uses. Myers said that while NGS provides an abundance of detailed data about sequenced microbes, it can be“ more powerful than you need for some applications.”

CDC’ s Office of Antimicrobial Resistance, headed by Jean Patel, PhD, D( ABMM), will be funding seven PHLs( to be announced this August) to develop referencelevel capacity to detect and characterize drug-resistant microbes, such as carbapenem-resistant Enterobacteriaceae, colistin-resistant mcr-1-positive E. coli and Candida auris, an emerging strain of yeast impervious to common antifungal drugs. Patel said NGS“ is very good for detecting resistance we already know about, but not so good for detecting resistance we don’ t know about.” And even when drug-resistance genes are found, phenotypic testing may still be necessary to confirm those genes are active and to detect resistance encoded by novel mechanisms.

This past April, Wisconsin’ s newborn screening( NBS) program had to make a decision. The State Laboratory of Hygiene was smack in the middle of a two-year pilot program to assess the use of a 240 mutation-panel as a second-tier NBS assay for cystic fibrosis( CF), an inherited condition linked to defects in the 250,000-base-pair-long CFTR gene.( Over 10 million Americans have a defect in one copy of the gene, making them CF carriers. About 35,000 have defects in both copies and have the disorder.)

Mei Wang Baker, MD, FACMG, who co-directs the NBS laboratory, said the pilot project had accumulated a“ good year” of data and experience, when the program’ s routine second-tier CF assay— a conventional molecular test with a much smaller mutation panel— was pulled from the market.“ So we had to make an earlier decision,” she said.

“ Our CF clinicians and NBS committee members really like this comprehensive [ pilot ] panel,” said Baker, citing its benefits:“ The additional mutations on the panel increase the likelihood of identifying the disease-causing mutation in true CF cases and puts us in a better position to identify disease carriers. In addition, the assay obtains all CFTR gene codon sequence information, and can be updated to include newly discovered mutations through software modifications without changing the assay.”

Still, PHLs are finding critical niches for NGS, even outside the microbiology laboratory.