An interpretable Graph-Regularized Optimal Transport Framework for Diagonal Single-Cell Integrative Analysis

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Abstract
Background: Recent advancements in single-cell omics technologies have enabled detailed characterization of cellular processes. However, coassay sequencing technologies remain limited, resulting in unpaired single-cell omics datasets with differing feature dimensions. Finding: We present GROTIA (Graph-Regularized Optimal Transport Framework for Diagonal Single-Cell Integrative Analysis), a computational method to align multi-omics datasets without requiring any prior correspondence information. GROTIA achieves global alignment through optimal transport while preserving local relationships via graph regularization. Additionally, our approach provides interpretability by deriving domain-specific feature importance from partial derivatives, highlighting key biological markers. Moreover, the transport plan between modalities can be leveraged for post-integration clustering, enabling a data-driven approach to discover novel cell subpopulations. Conclusions: We demonstrate GROTIA’s superior performance on four simulated and four real-world datasets, surpassing state-of-the-art unsupervised alignment methods and confirming the biological significance of the top features identified in each domain.
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Funding Information
  • NIH (R01 AG071470)
  • NIH (U19 AG074879)
  • NIH (U01 AG066833)
  • NIH (U01 AG068057)

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