Evidence map›Paper›PMID 40319040›Full record

ArticleNPJ genomic medicine2025

An outlier approach: advancing diagnosis of neurological diseases through integrating proteomics into multi-omics guided exome reanalysis.

Martin Man-Chun Chui, Anna Ka-Yee Kwong, Hiu Yu Cherie Leung, Chingyiu Pang, Ines F Scheller, Sheila Suet-Na Wong, Cheuk-Wing Fung, Vicente A Yépez, Julien Gagneur, Christopher Chun-Yu Mak and 1 more

Abstract read
In one paragraph

Article in NPJ genomic medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Long-read genome sequencing and multi-omics in aging and neurodegeneration.medRxiv : the preprint server for health sciences · 2025
    Article
  9. Review
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

11 authors.

Martin Man-Chun Chui *Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Anna Ka-Yee Kwong *Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Hiu Yu Cherie LeungDepartment of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Chingyiu PangDepartment of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Ines F SchellerSchool of Computation, Information and Technology, Technical University of Munich, Munich, Germany.
Sheila Suet-Na WongDepartment of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong SAR, China.
Cheuk-Wing FungDepartment of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong SAR, China.
Vicente A YépezSchool of Computation, Information and Technology, Technical University of Munich, Munich, Germany.
Julien GagneurSchool of Computation, Information and Technology, Technical University of Munich, Munich, Germany.
Christopher Chun-Yu MakDepartment of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Brian Hon-Yin ChungDepartment of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. bhychung@hku.hk.

Funding

Commissioned Paediatric Research at Hong Kong Children Hospital, HMRF PR-HKU-4Health and Medical Research Fund (HMRF) of the Hong Kong Food and Health Bureau 10212106Horizon Europe research and innovation programme, European Union N°101156595
6 · The paper itself

Abstract

Neurodevelopmental disorders (NDDs) often have unknown genetic causes. Current efforts in identifying disease-related genetic variants using exome or genome sequencing still lead to an excessive number of variants of uncertain significance (VUS). There is an increasing interest in transcriptomics and, more recently, proteomics for variant detection and interpretation. In this study, we integrated quantitative liquid chromatography-mass spectrometry proteomics, RNA sequencing, and exome reanalysis to resolve VUS and detect novel causal variants in 34 patients with undiagnosed NDDs, using the software PROTRIDER and DROP to detect protein outliers and RNA outliers, respectively. We obtained a diagnosis in 11 cases (32%) resulting from the increased amount of information provided by the two additional levels of omics (n = 5) and the updated literature evidence (n = 6). Our experience suggests the potential of this outlier-detection multi-omics workflow for improving diagnostic yield in NDDs and other rare disorders.

Identifiers

PMID40319040
PMCPMC12049463

What Socratic holds

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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 Socratic graph.