Implicit Hierarchical Tensor Decomposition of Single-Cell Four-Omics Data Reveals Cell-Type-Associated Enhancer–Promoter Regulatory Programs
Year: 2026
Type: preprint
Abstract: Single-cell multi-omics provides complementary views of gene regulation, but integrating modalities with natural features comprising enhancers, genes, and three-dimensional (3D) genomic loci remains challenging. This study developed an implicit hierarchical tensor decomposition framework and applied it to the CHARM single-cell four-omics mouse brain data (GSE303006) by jointly analyzing ATAC, H3K27ac, RNA, and reconstructed 3D enhancer–promoter (E–P) distances. After quality control, 730,969 E–P pairs, 42,669 enhancers, 16,239 genes, 391,435 20-kb bin pairs, and 4,258 cells were retained. Each modality was independently reduced to 20 components and mapped to an implicit 730,969 × 4,258 × 20 × 4 tensor, which was decomposed without materializing the full array. All 12 distinct cell components represented among the 100 largest Tucker core elements showed greater cell-type effects than replicate effects ( P = 2.44 × 10 −4 , sign test). A representative core linked the Inh Ndnf/Lamp5–Ex L3/4 IT cell axis to contrasting presynaptic-transmission and developmental/morphogenetic E–P programs. Backprojection showed reproducible ATAC, H3K27ac, and 3D effects across three biological replicates, whereas module-level RNA effects were weaker. The framework reveals the regulatory structure that is shared across molecular modalities while remaining distinct from any single molecular modality.
Authors: Y-H Taguchi, Turki Turki
Institutions: Chuo University, King Abdulaziz University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7204098015