Evidence map›Paper›PMID 39380081›Full record

ArticleHuman genomics2024

Leveraging large-scale datasets and single cell omics data to develop a polygenic score for cisplatin-induced ototoxicity.

Deanne Nixie R Miao, MacKenzie A P Wilke, John Pham, Feryal Ladha, Mansumeet Singh, Janilyn Arsenio, Emilia Luca, Alain Dabdoub, Wejian Yang, Jun J Yang and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Honokiol-mediated reversal of cisplatin-induced transcriptomic changes in outer hair cells.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026
    Article
  2. Review
  3. 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.

Deanne Nixie R MiaoDepartment of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
MacKenzie A P WilkeDepartment of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
John PhamDepartment of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Feryal LadhaDepartment of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Mansumeet SinghDepartment of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Janilyn ArsenioDepartment of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
Emilia LucaSunnybrook Research Institute, Toronto, ON, Canada.
Alain DabdoubSunnybrook Research Institute, Toronto, ON, Canada.
Wejian YangDepartment of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Jun J YangDepartment of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Britt I DrögemöllerDepartment of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada. britt.drogemoller@umanitoba.ca.

Funding

Canadian Foundation for Innovation, John R. Evans Leaders Fund (CFI-JELF) 37784Children's Hospital Research Institute of Manitoba STU2024-25-06CIHR CIHR PJT-183579
6 · The paper itself

Abstract

backgroundCisplatin-induced ototoxicity (CIO), characterized by irreversible and progressive bilateral hearing loss, is a prevalent adverse effect of cisplatin chemotherapy. Alongside clinical risk factors, genetic variants contribute to CIO and genome-wide association studies (GWAS) have highlighted the polygenicity of this adverse drug reaction. Polygenic scores (PGS), which integrate information from multiple genetic variants across the genome, offer a promising tool for the identification of individuals who are at higher risk for CIO. Integrating large-scale hearing loss GWAS data with single cell omics data holds potential to overcome limitations related to small sample sizes associated with CIO studies, enabling the creation of PGSs to predict CIO risk.

resultsWe utilized a large-scale hearing loss GWAS and murine inner ear single nuclei RNA-sequencing (snRNA-seq) data to develop two polygenic scores: a hearing loss PGS (PGS

conclusionThis study developed the first PGS for CIO using a large-scale hearing loss dataset and a biologically informed filter generated from cisplatin-treated murine inner ear snRNA-seq data. This innovative approach offers new avenues for developing PGSs for pharmacogenomic traits, which could contribute to the implementation of tailored therapeutic interventions. Further, our approach facilitated the identification of specific cochlear cells that may play critical roles in CIO. These novel insights will guide future research aimed at developing targeted therapeutic strategies to prevent CIO.

Indexed as

CisplatinGenome-Wide Association StudyHearing LossMultifactorial InheritanceOtotoxicityAnimalsAntineoplastic AgentsHumansMicePolymorphism, Single NucleotideSingle-Cell AnalysisAntineoplastic AgentsCisplatinCisplatin-induced ototoxicityPharmacogenomicsPolygenic scoresSingle-nuclei RNA-sequencing

Identifiers

PMID39380081
PMCPMC11463131

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LicenceCC BY
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Registered trials

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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.