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@ARTICLE{RuzJurado:306179,
author = {M. Ruz Jurado and D. Rodriguez Morales and E. Genetzakis
and F. B. Ardakani and L. Zanders and A. Fischer and F.
Buettner$^*$ and M. H. Schulz and S. Dimmeler and D. John},
title = {{D}ecoding heart failure subtypes with neural networks via
differential explanation analysis.},
journal = {Briefings in bioinformatics},
volume = {26},
number = {6},
issn = {1467-5463},
address = {Oxford [u.a.]},
publisher = {Oxford University Press},
reportid = {DKFZ-2025-02419},
pages = {bbaf581},
year = {2025},
abstract = {Single-cell transcriptomics offers critical insights into
the molecular mechanisms of heart failure (HF) with reduced
or preserved ejection fraction. However, understanding these
mechanisms is hindered by the growing complexity of
single-cell data and the difficulty in unmasking meaningful
differential gene signatures among HF types. Machine
learning, particularly deep neural networks (NNs), address
these challenges by learning transcriptional patterns,
reconstructing expression profiles and effectively
classifying cells but often lacks interpretability. Recent
advances in explainable AI (XAI) offer tools to clarify
model decisions. Yet pinpointing differentially regulated
genes with these tools remains challenging. We introduce a
novel method to identify differentially explained genes
(DXGs) based on importance scores derived from custom-built
NNs. We highlight the superiority of DXGs in identifying HF
subtypes-specific pathways that provide new insights into
different types of HF. Offering a robust foundation for
future research and therapeutic exploration in expanding
transcriptome atlases.},
keywords = {Heart Failure: genetics / Heart Failure: classification /
Heart Failure: metabolism / Humans / Neural Networks,
Computer / Transcriptome / Gene Expression Profiling /
Machine Learning / Computational Biology: methods / deep
neural networks (Other) / differential gene expression
(Other) / explainable artificial intelligence (Other) /
heart failure subtypes (Other)},
cin = {FM01},
ddc = {004},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41222558},
pmc = {pmc:PMC12610404},
doi = {10.1093/bib/bbaf581},
url = {https://inrepo02.dkfz.de/record/306179},
}