Evaluating use of changing technologies for rapid next-generation sequencing in pediatrics

• Type of Material: Article
• Authors: Rachel Palmquist, University of Utah; Sabrina Malone Jenkins, Primary Children’s Center for Personalized Medicine; Dawn Bentley, University of Utah; Christine Miller, ARUP Laboratories; Rong Mao, ARUP Laboratories; Bailey Meibos, Primary Children’s Center for Personalized Medicine; Pinar Bayrak-Toydemir, ARUP Labs; Tatiana Tvrdik, Emory University; Lincoln D Nadauld, Intermountain Healthcare; Steven B Bleyl, University of Utah; Shimul Chowdhury, Rady Children’s Hospital San Diego; Betsy Ostrander, University of Utah; Josue Flores-Daboub, University of Utah; Nicola Longo, University of Utah; Martin Tristani-Firouzi, University of Utah; Charlotte Hobbs, Rady Childrens Hospital San Diego; Joshua L Bonkowsky, University of Utah; Luca Brunelli, University of Utah
• Language: English
• Date: 2022-02-03
• Publisher: SPRINGERNATURE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc
• Final Published Version (URL): http://dx.doi.org/10.1038/s41390-022-01965-5
• Title of Journal or Parent Work: PEDIATRIC RESEARCH
• Volume: 92
• Issue: 5
• Start Page: 1364
• End Page: 1369
• Keywords: Science & Technology; CARE; Life Sciences & Biomedicine; LABORATORIES; Pediatrics; OUTCOMES

Abstract

Background: Rapid next-generation sequencing (NGS) offers the potential to shorten the diagnostic process and improve the care of acutely ill children. The goal of this study was to report our findings, including benefits and limitations, of a targeted NGS panel and rapid genome sequencing (rGS) in neonatal and pediatric acute clinical care settings. Methods: Retrospective analysis of patient characteristics, diagnostic yields, turnaround time, and changes in management for infants and children receiving either RapSeq, a targeted NGS panel for 4500+ genes, or rGS, at the University of Utah Hospital and Primary Children’s Hospital, from 2015 to 2020. Results: Over a 5-year period, 142 probands underwent rapid NGS: 66 received RapSeq and 76 rGS. Overall diagnostic yield was 39%. In the majority of diagnostic cases, there were one or more changes in clinical care management. Of note, 7% of diagnoses identified by rGS would not have been identified by RapSeq. Conclusions: Our results indicate that rapid NGS impacts acute pediatric care in real-life clinical settings. Although affected by patient selection criteria, diagnostic yields were similar to those from clinical trial settings. Future studies are needed to determine relative advantages, including cost, turnaround time, and benefits for patients, of each approach in specific clinical circumstances. Impact: The use of comprehensive Mendelian gene panels and genome sequencing in the clinical setting allows for early diagnosis of patients in neonatal, pediatric, and cardiac intensive care units and impactful change in management.Diagnoses led to significant changes in management for several patients in lower acuity inpatient units supporting further exploration of the utility of rapid sequencing in these settings.This study reviews the limitations of comparing sequencing platforms in the clinical setting and the variables that should be considered in evaluating diagnostic rates across studies.