Evidence map›Paper›PMID 33093641›Full record

ArticleJournal of human genetics2021

Clinical and technical assessment of MedExome vs. NGS panels in patients with suspected genetic disorders in Southwestern Ontario.

Erfan Aref-Eshghi, Jennifer Kerkhof, Deana Alexis Carere, Michael Volodarsky, Pratibha Bhai, Samantha Colaiacovo, Maha Saleh, Michelle Caudle, Natalya Karp, Chitra Prasad and 5 more

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PubMed Publisher
In one paragraph

Article in Journal of human genetics, 2021. 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
0.4field-weighted citation impact, top 32% of its field
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, 2 citations in OpenAlex.

  1. 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

15 authors at 3 institutions in 1 country.

Erfan Aref-EshghiMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, Canada.
Jennifer KerkhofMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, Canada.
Deana Alexis CarereMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, Canada.
Michael VolodarskyMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, Canada.
Pratibha BhaiMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, Canada.
Samantha ColaiacovoMedical Genetics Program of Southwestern Ontario, Victoria Hospital, London Health Sciences Centre, London, ON, Canada.
Maha SalehMedical Genetics Program of Southwestern Ontario, Victoria Hospital, London Health Sciences Centre, London, ON, Canada.
Michelle CaudleMedical Genetics Program of Southwestern Ontario, Victoria Hospital, London Health Sciences Centre, London, ON, Canada.
Natalya KarpMedical Genetics Program of Southwestern Ontario, Victoria Hospital, London Health Sciences Centre, London, ON, Canada.
Chitra PrasadMedical Genetics Program of Southwestern Ontario, Victoria Hospital, London Health Sciences Centre, London, ON, Canada.
Tugce BalciMedical Genetics Program of Southwestern Ontario, Victoria Hospital, London Health Sciences Centre, London, ON, Canada.
Hanxin LinMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, Canada.
Craig CampbellDepartment of Pediatric Neurology, Children's Hospital, London Health Science Centre, London, ON, Canada.
Victoria Mok SiuMedical Genetics Program of Southwestern Ontario, Victoria Hospital, London Health Sciences Centre, London, ON, Canada.
Bekim SadikovicMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, Canada. Bekim.Sadikovic@lhsc.on.ca.
London Health Sciences Centre · CAVictoria Hospital · CAWestern University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The adaptation of a broad genomic sequencing approach in the clinical setting has been accompanied by considerations regarding the clinical utility, technical performance, and diagnostic yield compared to targeted genetic approaches. We have developed MedExome, an integrated framework for sequencing, variant calling (SNVs, Indels, and CNVs), and clinical assessment of ~4600 medically relevant genes. We compared the technical performance of MedExome with the whole-exome and targeted gene-panel sequencing, assessed the reasons for discordance, and evaluated the added clinical yield of MedExome in a cohort of unresolved subjects suspected of genetic disease. Our analysis showed that despite a higher average read depth in panels (3058 vs. 855), MedExome yielded full coverage of the enriched regions (>20X) and 99% variant concordance rate with panels. The discordance rate was associated with low-complexity regions, high-GC content, and low allele fractions, observed in both platforms. MedExome yielded full sensitivity in detecting clinically actionable variants, and the assessment of 138 patients with suspected genetic conditions resulted in 76 clinical reports (31 full [22.1%], 3 partial, and 42 uncertain/possible molecular diagnoses). MedExome sequencing has comparable performance in variant detection to gene panels. Added diagnostic yield justifies expanded implementation of broad genomic approaches in unresolved patients; however, cost-benefit and health systems impact warrants assessment.

Indexed as

AllelesBase CompositionConsanguinityDNA Copy Number VariationsExomeExome SequencingGene LibraryGenetic Diseases, InbornGenetic VariationHigh-Throughput Nucleotide SequencingHomozygoteHumansINDEL MutationMolecular Diagnostic TechniquesOntarioPoint Mutation

Identifiers

PMID33093641
OpenAlexW3094599441

What OpenQuestion holds

Textmetadata
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.