Evidence map›Paper›PMID 34556655›Full record

ArticleNPJ genomic medicine2021

Application of full-genome analysis to diagnose rare monogenic disorders.

Joseph T Shieh, Monica Penon-Portmann, Karen H Y Wong, Michal Levy-Sakin, Michelle Verghese, Anne Slavotinek, Renata C Gallagher, Bryce A Mendelsohn, Jessica Tenney, Daniah Beleford and 10 more

Erratum issued Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ genomic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT05295277 (Validation of Optical Genome Mapping for the Identification of Constitutional Genomic Variants in a Postnatal Cohort), which is not on this map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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.

NCT05295277 unknown statusnot on this map

Validation of Optical Genome Mapping for the Identification of Constitutional Genomic Variants in a Postnatal Cohort

TypeobservationalSponsorBionano GenomicsRan2020 to 2024Enrolled1,000ConditionsDevelopmental Disability, Intellectual Disability, Autism Spectrum Disorder, Congenital AnomalyArmsStandard of care genetic testing group
3 · Its place in the literature

Who cites it

25 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Two-Compound Heterozygous Deletions AffectingMolecular syndromology · 2024
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Precision diagnostics in children.Cambridge prisms. Precision medicine · 2023
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Joseph T Shieh *Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA. Joseph.shieh2@ucsf.edu.ORCID http://orcid.org/0000-0003-0746-6084
Monica Penon-Portmann *Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3011-440X
Karen H Y Wong *Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1648-1414
Michal Levy-SakinCardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
Michelle VergheseCardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5635-7365
Anne SlavotinekInstitute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-7053-2449
Renata C GallagherInstitute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1611-0354
Bryce A MendelsohnDivision of Medical Genetics, Pediatrics, Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8174-5116
Jessica TenneyDivision of Medical Genetics, Pediatrics, Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.
Daniah BelefordDivision of Medical Genetics, Pediatrics, Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.
Hazel PerryDivision of Medical Genetics, Pediatrics, Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.
Stephen K ChowCardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
Andrew G SharoBiophysics Graduate Group, University of California Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-6533-8385
Steven E BrennerDepartment of Plant and Microbial Biology, University of California Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-7559-6185
Zhongxia QiDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Jingwei YuDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Ophir D KleinInstitute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6254-7082
David MartinChildren's Hospital Oakland Research Institute, Benioff Children's Hospital Oakland, University of California San Francisco, Oakland, CA, USA.
Pui-Yan KwokInstitute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-5087-3059
Dario BoffelliChildren's Hospital Oakland Research Institute, Benioff Children's Hospital Oakland, University of California San Francisco, Oakland, CA, USA.

Funding

UCSF Nutrition Obesity Research CenterP30DK098722 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHRISTIAN VAISSE · 2015 to 2026
$14.6M
Single molecule DNA mapping for genome and CNV analysisR01HG005946 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KWOK, PUI-YAN, XIAO, MING · 2010 to 2021
$6.5M
National Science Foundation (NSF) DGE 1752814NHGRI NIH HHS R01 HG005946NIDDK NIH HHS P30 DK098722
6 · The paper itself

Abstract

Current genetic testenhancer and narrows the diagnostic intervals for rare diseases provide a diagnosis in only a modest proportion of cases. The Full-Genome Analysis method, FGA, combines long-range assembly and whole-genome sequencing to detect small variants, structural variants with breakpoint resolution, and phasing. We built a variant prioritization pipeline and tested FGA's utility for diagnosis of rare diseases in a clinical setting. FGA identified structural variants and small variants with an overall diagnostic yield of 40% (20 of 50 cases) and 35% in exome-negative cases (8 of 23 cases), 4 of these were structural variants. FGA detected and mapped structural variants that are missed by short reads, including non-coding duplication, and phased variants across long distances of more than 180 kb. With the prioritization algorithm, longer DNA technologies could replace multiple tests for monogenic disorders and expand the range of variants detected. Our study suggests that genomes produced from technologies like FGA can improve variant detection and provide higher resolution genome maps for future application.

Identifiers

PMID34556655
PMCPMC8460793

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.