Evidence map›Paper›PMID 41715921›Full record

ArticleHGG advances2026

Scaling genomic reanalysis to unlock diagnoses and transform rare disease care.

Shira Rockowitz, Wanqing Shao, Courtney French, Tina K Truong, Jacob Hagen, Rylee McGonigle, Alexa Geltzeiler, Beth Sheidley, Lacey Smith, Alissa M D'Gama and 38 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in HGG advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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1 citing paper in PubMed.

  1. Article
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5 · Who and what money

Authors and funding

48 authors.

Shira RockowitzChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
Wanqing ShaoChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA.
Courtney FrenchChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA.
Tina K TruongChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
Jacob HagenChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
Rylee McGonigleChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA.
Alexa GeltzeilerDepartment of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
Beth SheidleyBoston Children's Hospital, Department of Neurology, Boston, MA, USA.
Lacey SmithBoston Children's Hospital, Department of Neurology, Boston, MA, USA.
Alissa M D'GamaChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Newborn Medicine, Boston, MA, USA.
Mira IronsChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Janet ChouChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
Joan StolerChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Amy KritzerDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Lance RodanHarvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Boston Children's Hospital, Department of Neurology, Boston, MA, USA.
Akiko ShimamuraChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Hematology and Oncology, Boston Children's Hospital, Boston, MA, USA; Dana Farber Cancer Institute, Boston, MA, USA.
Olaf BodamerChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Stephanie SacharowDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Janet S SoulChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Department of Neurology, Boston, MA, USA.
Siddharth SrivastavaChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Department of Neurology, Boston, MA, USA; Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Boston, MA, USA.
Amy Roberts KennedyChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Aya Abu-El-HaijaDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Abbe LaiBoston Children's Hospital, Department of Neurology, Boston, MA, USA.
Heather OlsonHarvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Boston Children's Hospital, Department of Neurology, Boston, MA, USA.
Jane JuusolaGeneDx, LLC, Gaithersburg, MD, USA.
Erin RyanGeneDx, LLC, Gaithersburg, MD, USA.
Bethany FriedmanGeneDx, LLC, Gaithersburg, MD, USA.
Anupama SinghChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA.
Cliff LiChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA.
Rittika MallikChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA.
Gwendolyn StricklandChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
Gillian PrinzingBoston Children's Hospital, Department of Neurology, Boston, MA, USA.
Alisa MoHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Department of Neurology, Boston, MA, USA.
Anne O'Donnell-LuriaChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jeff BoltonHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Department of Neurology, Boston, MA, USA.
Philip M BooneChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
William BruckerDepartment of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Michael DuyzendDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Sonal MahidaBoston Children's Hospital, Department of Neurology, Boston, MA, USA.
David T MillerDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Jacklyn OmorodionDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Jeanette PetitDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
Jonathan PickerDepartment of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, USA.
Annapurna PoduriChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Department of Neurology, Boston, MA, USA.
Colleen CarlstonDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Monica H WojcikChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Boston Children's Hospital, Division of Newborn Medicine, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Piotr SlizChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Division of Molecular Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Wendy K ChungChildren's Rare Disease Collaborative, Boston Children's Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: wendy.chung@childrens.harvard.edu.

Funding

Systems Biology of Bone Marrow Failure and MDS for Precision MedicineRC2DK122533 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI FIGUEROA, MARIA EUGENIA, FLEMING, MARK D · 2019 to 2023
$6.4M
NIDDK NIH HHS RC2 DK122533
6 · The paper itself

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.

Indexed as

GenomicsRare DiseasesComputational BiologyGenetic TestingHumansclinical genomics infrastructurediagnostic yeild improvementES/GSexome and genome sequencinggenomic reanalysismachine learning in variant prioritizationPGRprecision medicine implementationproactive genomic reanalysisrare disease diagnosticsscalable genomic medicinevariant reclassification

Identifiers

PMID41715921
PMCPMC12993396

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