# MOMHCA-SG: a multi-head cross-attention and similar graph convolutional network framework for Alzheimer’s disease cell type classification

**Authors:** Yan Qian, Wei Kong, Shuaiqun Wang, Gen Wen, Yaling Yu

PMC · DOI: 10.3389/fnins.2026.1728558 · Frontiers in Neuroscience · 2026-02-16

## TL;DR

This paper introduces a new framework for classifying cell types in Alzheimer's disease by integrating multiple types of biological data.

## Contribution

MOMHCA-SG is a novel multi-omics integration framework using cross-attention and graph convolutional networks for Alzheimer’s cell type classification.

## Key findings

- MOMHCA-SG achieves high performance with ARI of 0.99, NMI of 0.98, and AMI of 0.98.
- The framework identifies key genes and pathways involved in Alzheimer’s disease pathogenesis.
- It effectively integrates heterogeneous omics data and captures cross-modality relationships.

## Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with di-verse cellular and molecular characteristics. Due to its heterogeneous nature, early detection and understanding of AD are challenging, and conventional unimodal approaches often fail to capture the intricate interactions across different biological layers.

We propose MOMHCA-SG, a novel multi-omics integration framework that combines a multi-head cross-attention mechanism (MHCA) with a graph convolutional network (GCN) guided by similarity network fusion (SNF). The framework first employs an autoencoder (AE) for dimensionality reduction and feature extraction, followed by MHCA to model inter-omic dependencies. A contrastive learning strategy is then utilized to refine latent representations, while the GCN performs final cell-type classification using fused similarity networks derived from both scRNA-seq and scATAC-seq datasets related to AD.

Extensive experiments on publicly available AD datasets demonstrate that MOMHCA-SG attains superior performance in both integration and classification tasks, achieving an ARI of 0.99, NMI of 0.98, and AMI of 0.98, with classification accuracy exceeding 0.98. Downstream bioinformatics analyses further identify key genes and signaling pathways potentially involved in AD pathogenesis, supporting the framework’s biological interpretability.

MOMHCA-SG effectively preserves feature integrity during high-dimensional processing, dynamically integrates heterogeneous omics data, and captures cross-modality relationships. These capabilities highlight its potential as a powerful tool for elucidating disease mechanisms and advancing precision medicine in neurodegenerative disorders.

## Linked entities

- **Diseases:** Alzheimer’s disease (MONDO:0004975)

## Full-text entities

- **Genes:** PIK3CD (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) [NCBI Gene 5293] {aka APDS, IMD14, IMD14A, IMD14B, P110DELTA, PI3K}, ITGB2 (integrin subunit beta 2) [NCBI Gene 3689] {aka CD18, LAD, LCAMB, LFA-1, MAC-1, MF17}, SYK (spleen associated tyrosine kinase) [NCBI Gene 6850] {aka IMD82, p72-Syk}, ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, DOCK8 (dedicator of cytokinesis 8) [NCBI Gene 81704] {aka HEL-205, HIES2, MRD2, ZIR8}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, PRKCB (protein kinase C beta) [NCBI Gene 5579] {aka PKC-beta, PKCB, PKCI(2), PKCbeta, PRKCB1, PRKCB2}, OXT (oxytocin/neurophysin I prepropeptide) [NCBI Gene 5020] {aka OT, OT-NPI, OXT-NPI}, FYB1 (FYN binding protein 1) [NCBI Gene 2533] {aka ADAP, FYB, PRO0823, SLAP-130, SLAP130, THC3}, RAP1A (RAP1A, member of RAS oncogene family) [NCBI Gene 5906] {aka C21KG, G-22K, KREV-1, KREV1, RAP1, SMGP21}, ARHGAP15 (Rho GTPase activating protein 15) [NCBI Gene 55843] {aka BM046}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, ATP8B4 (ATPase phospholipid transporting 8B4 (putative)) [NCBI Gene 79895] {aka ATPIM}, APBB1IP (amyloid beta precursor protein binding family B member 1 interacting protein) [NCBI Gene 54518] {aka INAG1, PREL1, RARP1, RIAM}, FYN (FYN proto-oncogene, Src family tyrosine kinase) [NCBI Gene 2534] {aka SLK, SYN, p59-FYN}, LYN (LYN proto-oncogene, Src family tyrosine kinase) [NCBI Gene 4067] {aka JTK8, SAIDV, p53Lyn, p56Lyn}
- **Diseases:** neuronal loss (MESH:D009410), cognitive and memory deficits (MESH:D003072), gliosis (MESH:D005911), SNF (MESH:C536318), MF (MESH:C567116), toxicity (MESH:D064420), neurodegenerative (MESH:D019636), inflammation (MESH:D007249), cancer (MESH:D009369), AD (MESH:D000544), neuroinflammation (MESH:D000090862)
- **Chemicals:** lipid (MESH:D008055), calcium (MESH:D002118), phospholipid (MESH:D010743)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12950759/full.md

## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12950759/full.md

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Source: https://tomesphere.com/paper/PMC12950759