Scaling genomic reanalysis to unlock diagnoses and transform rare disease care
Year: 2026
Type: article
Abstract: Genomic reanalysis can identify causative variants for rare diseases as patient phenotypes evolve and gene-disease knowledge expands. Despite its diagnostic value, routine reanalysis is limited by clinician capacity, lack of patient follow-up, data silos, cost, and lack of availability of clinical data to testing laboratories that are not obligated to conduct reanalysis. The Children's Rare Disease Collaborative at Boston Children's Hospital (BCH) has integrated genomic and phenotypic data from over 15,500 patients into a clinician-facing platform. Leveraging this infrastructure, we developed a Proactive Genomic Reanalysis (PGR) workflow at BCH for clinical sequencing data that is centralized, semi-automated, and clinically integrated. Here, we report initial results and outline required resources and transferable insights applicable to other healthcare settings. Initial pilot implementation, applied to a subset of clinical sequencing patients' data, revealed practical challenges, notably clinician turnover and patient recontact difficulties. Of 42 patients' candidate variants discovered by the PGR bioinformatics pipeline and returned to treating clinicians, 33 were determined to have a high suspicion of disease causality and an additional 3 were determined to be candidate variant of uncertain significance. A process to generate reports and return results to patients was initiated when applicable. Although the initial pilot implementation was limited, the PGR bioinformatics pipeline is designed to be utilized iteratively, making reanalysis a continuing process. This work highlights the feasibility and impact of centralized PGR processes and the potential for healthcare institutions to scale genomic reanalysis.
Authors: Shira Rockowitz, Wanqing Shao, Courtney French, Tina K. Truong, Jacob Hagen, Rylee McGonigle, Alexa Geltzeiler, Beth Sheidley, Lacey Smith, Alissa M. D’Gama, Mira Irons, Janet Chou, Joan Stoler, Amy Kritzer, Lance Rodan, Akiko Shimamura, Olaf Bodamer, Stephanie Sacharow, Janet S. Soul, Siddharth Srivastava, Amy Roberts Kennedy, Aya Abu-El-Haija, Abbe Lai, Heather Olson, Jane Juusola, Erin Ryan, Bethany Friedman, Anupama Singh, Cliff Li, Rittika Mallik, Gwendolyn Strickland, Gillian Prinzing, Alisa Mo, Anne O’Donnell-Luria, Jeff Bolton, Philip M. Boone, William Brucker, Michael Duyzend, Sonal Mahida, David T. Miller, Jacklyn Omorodion, Jeanette Petit, Jonathan Picker, Annapurna Poduri, Colleen Carlston, Monica H. Wojcik, Piotr Sliz, Wendy K. Chung
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,300
OpenAlex ID: W7130446609