Evidence map›Paper›PMID 40661289›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Scalable automated reanalysis of genomic data in research and clinical rare disease cohorts.

Matthew J Welland, K D Ahlquist, Paul De Fazio, Christina Austin-Tse, Lynn Pais, Laura Wedd, Samantha Bryen, Rocio Rius, Michael Franklin, Caitlin Morrison and 27 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors.

Matthew J WellandCentre for Population Genomics, Garvan Institute of Medical Research and UNSW Sydney, 384 Victoria Street, Sydney, Australia.
K D AhlquistCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Paul De FazioVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.
Christina Austin-TseCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Lynn PaisProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Laura WeddCentre for Population Genomics, Garvan Institute of Medical Research and UNSW Sydney, 384 Victoria Street, Sydney, Australia.
Samantha BryenCentre for Population Genomics, Garvan Institute of Medical Research and UNSW Sydney, 384 Victoria Street, Sydney, Australia.
Rocio RiusCentre for Population Genomics, Garvan Institute of Medical Research and UNSW Sydney, 384 Victoria Street, Sydney, Australia.ORCID 0000-0002-9871-3126
Michael FranklinCentre for Population Genomics, Garvan Institute of Medical Research and UNSW Sydney, 384 Victoria Street, Sydney, Australia.
Caitlin MorrisonCentre for Population Genomics, Garvan Institute of Medical Research and UNSW Sydney, 384 Victoria Street, Sydney, Australia.
Giles HallData Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02141.
Laura GauthierCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Alex BloemendalProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
David I FrancisVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.
Andrew J MallettTownsville Hospital and Health Service, Townsville, QLD, Australia.
Amali MallawaarachchiClinical Genetics Service, Royal Prince Alfred Hospital, Sydney, Australia.
Paul J LockhartMurdoch Children's Research Institute, Melbourne, Australia.ORCID 0000-0003-2531-8413
Richard LeventerMurdoch Children's Research Institute, Melbourne, Australia.
Ingrid E SchefferUniversity of Melbourne, Melbourne, Australia.
Katherine B HowellMurdoch Children's Research Institute, Melbourne, Australia.
Karin S KassahnDepartment of Genetics and Molecular Pathology, SA Pathology, Adelaide, Australia.
Hamish S ScottDepartment of Genetics and Molecular Pathology, SA Pathology, Adelaide, Australia.
Julie McGaughranGenetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
John ChristodoulouMurdoch Children's Research Institute, Melbourne, Australia.ORCID 0000-0002-8431-0641
David R ThorburnVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.
Bryony A ThompsonDepartment of Pathology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Chirag V PatelGenetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
Greg SmithMicrosoft Research, Redmond, WA, USA.
Anne O'Donnell-LuriaCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0001-6418-9592
Simon SadedinVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.
Heidi L RehmCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Sebastian LunkeVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.
Jeremiah WanderMicrosoft Research, Redmond, WA, USA.
Kaitlin E SamochaCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-1704-3352
Cas SimonsCentre for Population Genomics, Garvan Institute of Medical Research and UNSW Sydney, 384 Victoria Street, Sydney, Australia.
Daniel G MacArthurCentre for Population Genomics, Garvan Institute of Medical Research and UNSW Sydney, 384 Victoria Street, Sydney, Australia.
Zornitza StarkVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.

Funding

Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
Broad Institute Mendelian Genomic Research CenterU01HG011755 · NHGRI · BROAD INSTITUTE, INC. · PI Anne O'Donnell-Luria, MICHAEL E TALKOWSKI · 2021 to 2026
$14.6M
A powerful web-based discovery platform for rare disease geneticsR01HG009141 · NHGRI · BROAD INSTITUTE, INC. · PI QUINLAN, AARON R, REHM, HEIDI L · 2017 to 2020
$2.9M
NHGRI NIH HHS R01 HG009141NHGRI NIH HHS U01 HG011755NHGRI NIH HHS UM1 HG008900
6 · The paper itself

Abstract

Reanalysis of genomic data in rare disease is highly effective in increasing diagnostic yields but remains limited by manual approaches. Automation and optimization for high specificity will be necessary to ensure scalability, adoption and sustainability of iterative reanalysis. We developed a publicly available automated tool, Talos, and validated its performance using data from 1,089 individuals with rare genetic disease. Trio-based analysis identified 86% of known in-scope diagnoses, returning one variant per case on average. Variant burden reduced to one variant per 200 cases on iterative monthly reanalysis cycles. Application to an unselected cohort of 4,735 undiagnosed individuals identified 248 diagnoses (5.2% yield): 73 (29%) due to new gene-disease relationships, 56 (23%) due to new variant-level evidence, and 119 (48%) due to improved filtering and analysis strategies. Our automated, iterative reanalysis model, applied to thousands of rare disease patients, demonstrates the feasibility of delivering frequent, systematic reanalysis at scale.

Identifiers

PMID40661289
PMCPMC12258758

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.