ArticleNature communications2024
Multiscale mapping of transcriptomic signatures for cardiotoxic drugs.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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.
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Who cites it
10 citing papers in PubMed.
- A Ponatinib-Associated Transcriptomic Signature: Implications for Cardiovascular Toxicity.International journal of molecular sciences · 2026Article
- Integrating Human Intestinal Organoids into FDA's New Approach Methodologies for Drug Discovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- predicTox: an integrated database of clinical risk frequencies and human gene expression signatures for cardiotoxic drugs.Database : the journal of biological databases and curation · 2026Article
- Advances in Cytotoxicity Testing: From In Vitro Assays to In Silico Models.International journal of molecular sciences · 2025Review
- Immunotherapy-Associated Cardiotoxicity: Current Insights and Future Directions for Precision Cardio-Oncology.Cancers · 2025Review
- Drug Discovery and Development for Heart Failure Using Multi-Omics Approaches.International journal of molecular sciences · 2025Review
- MBC PathNet: integration and visualization of networks connecting functionally related pathways predicted from transcriptomic and proteomic datasets.Bioinformatics advances · 2025Article
- Multiscale mapping of transcriptomic signatures for cardiotoxic drugs.Nature communications · 2024Article
- Informing Hazard Identification and Risk Characterization of Environmental Chemicals by Combining Transcriptomic and Functional Data from Human-Induced Pluripotent Stem-Cell-Derived Cardiomyocytes.Chemical research in toxicology · 2024Article
- Integrative Cross-platform Analysis of Kinase Inhibitor Effects on Statin-relevant Cardioprotective Pathways in Human Cardiomyocytes.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
Drug-induced gene expression profiles can identify potential mechanisms of toxicity. We focus on obtaining signatures for cardiotoxicity of FDA-approved tyrosine kinase inhibitors (TKIs) in human induced-pluripotent-stem-cell-derived cardiomyocytes, using bulk transcriptomic profiles. We use singular value decomposition to identify drug-selective patterns across cell lines obtained from multiple healthy human subjects. Cellular pathways affected by cardiotoxic TKIs include energy metabolism, contractile, and extracellular matrix dynamics. Projecting these pathways to published single cell expression profiles indicates that TKI responses can be evoked in both cardiomyocytes and fibroblasts. Integration of transcriptomic outlier analysis with whole genomic sequencing of our six cell lines enables us to correctly reidentify a genomic variant causally linked to anthracycline-induced cardiotoxicity and predict genomic variants potentially associated with TKI-induced cardiotoxicity. We conclude that mRNA expression profiles when integrated with publicly available genomic, pathway, and single cell transcriptomic datasets, provide multiscale signatures for cardiotoxicity that could be used for drug development and patient stratification.
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Registered trials
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