Evidence map›Paper›PMID 33303739›Full record

ArticleNPJ genomic medicine2020

A flexible computational pipeline for research analyses of unsolved clinical exome cases.

Timo Lassmann, Richard W Francis, Alexia Weeks, Dave Tang, Sarra E Jamieson, Stephanie Broley, Hugh J S Dawkins, Lauren Dreyer, Jack Goldblatt, Tudor Groza and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ genomic medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Neptune: an environment for the delivery of genomic medicine.Genetics in medicine : official journal of the American College of Medical Genetics · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Timo LassmannTelethon Kids Institute, University of Western Australia, Perth, WA, Australia. Timo.Lassmann@telethonkids.org.au.ORCID http://orcid.org/0000-0002-0138-2691
Richard W FrancisTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Alexia WeeksTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Dave TangTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Sarra E JamiesonTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Stephanie BroleyGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Hugh J S DawkinsOffice of Population Health Genomics, Public Health Division, Department of Health, Government of Western Australia, Perth, WA, Australia.
Lauren DreyerGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Jack GoldblattGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Tudor GrozaTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Benjamin KamienGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Cathy Kiraly-BorriGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Fiona McKenzieGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Lesley MurphyRare Voices Australia, Sydney, Australia.
Nicholas PachterGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Gargi PathakGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Cathryn PoultonGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Amanda SamanekGaRDN Genetics and Rare Diseases Network, Booragoon, WA, Australia.
Rachel SkossTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.ORCID http://orcid.org/0000-0002-7033-5063
Jennie SleeGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Sharron TownshendGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Michelle WardGenetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.
Gareth S BaynamTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Jenefer M BlackwellTelethon Kids Institute, University of Western Australia, Perth, WA, Australia. Jenefer.Blackwell@telethonkids.org.au.ORCID http://orcid.org/0000-0002-0784-7277

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Exome sequencing has enabled molecular diagnoses for rare disease patients but often with initial diagnostic rates of ~25-30%. Here we develop a robust computational pipeline to rank variants for reassessment of unsolved rare disease patients. A comprehensive web-based patient report is generated in which all deleterious variants can be filtered by gene, variant characteristics, OMIM disease and Phenolyzer scores, and all are annotated with an ACMG classification and links to ClinVar. The pipeline ranked 21/34 previously diagnosed variants as top, with 26 in total ranked ≤7th, 3 ranked ≥13th; 5 failed the pipeline filters. Pathogenic/likely pathogenic variants by ACMG criteria were identified for 22/145 unsolved cases, and a previously undefined candidate disease variant for 27/145. This open access pipeline supports the partnership between clinical and research laboratories to improve the diagnosis of unsolved exomes. It provides a flexible framework for iterative developments to further improve diagnosis.

Identifiers

PMID33303739
PMCPMC7730424

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.