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 .