LATTICE通过图自监督学习整合多组学空间数据,提升组织微环境解析精度。
LATTICE: Graph Self-Supervised Learning for Multimodal Spatial Omics Integration

- 构建空间邻域图,用TransformerConv模型联合训练多模态特征
- 加入单细胞多组学数据使聚类一致性提升15.7%(ARI),空间连续性增17.4%
- 适合研究肿瘤微环境、表观遗传调控的跨模态分析人员
空间分辨组学日益融合转录组与表观基因组数据,但下游分析仍多依赖单模态流程。我们提出LATTICE(组织层面与转录信息的潜在对齐框架),一种基于图的自监督方法,从统一的多模态特征中学习位点级表示。LATTICE整合每个Visium位点的五种对齐模态:Visium RNA、scMultiome RNA、scMultiome ATAC、空间ATAC和空间CUT&Tag,涵盖空间转录组、单细胞推断的调控活性及原位染色质与组蛋白状态。通过构建空间邻域图,并以掩码重建、跨模态对齐和空间平滑为优化目标,训练TransformerConv编码器。在来自匿名临床合作方的11例黑色素瘤队列(共54,912个位点)上,LATTICE展现出稳定优化行为、可重复嵌入及全样本多模态整合能力。仅将scMultiome RNA加入Visium RNA,即显著提升与Space Ranger聚类的一致性(ARI +0.157,NMI +0.143,空间连续性 +0.174)。添加更多模态进一步提高空间连续性和多模态效用评分(MUS),但有时降低与基于RNA的参考标签一致性,可能因嵌入同时捕捉了超越转录组相似性的染色质与调控结构。结果表明LATTICE是实用且实证支持的多模态空间组学整合框架,也凸显更强监督与更广外部基准的必要性。
原文摘要 · Abstract (English)
Spatially resolved omics studies increasingly combine transcriptomic and epigenomic assays, yet downstream analysis is often still performed using single-modality pipelines. We present LATTICE (Latent Alignment of Tissue-level and Transcriptomic Information for Cross-modal Embedding), a graph-based self-supervised framework that learns spot-level representations from harmonized multimodal features. LATTICE integrates five aligned modality blocks per Visium spot: Visium RNA, scMultiome RNA, scMultiome ATAC, spatial ATAC, and spatial CUT\&Tag. These modalities capture spatial transcriptomic measurements, single-cell inferred regulatory activity, and in situ chromatin and histone states within a unified lattice representation. LATTICE constructs a spatial neighborhood graph and trains a TransformerConv encoder using masked reconstruction, cross-modal alignment, and spatial smoothness objectives. On a private 11-sample melanoma cohort from an anonymized clinical collaborator comprising 54{,}912 total spots, LATTICE demonstrated stable optimization behavior, reproducible embeddings across analysis seeds, and complete multimodal integration across all samples. Adding scMultiome RNA to Visium RNA alone substantially improved concordance with Space Ranger clusters across 11 runs (adjusted Rand index [ARI] +0.157, normalized mutual information [NMI] +0.143, and spatial contiguity +0.174). Additional modalities further improved spatial contiguity and multimodal utility score (MUS), although they sometimes reduced agreement with RNA-derived reference labels, likely because the learned embeddings captured chromatin and regulatory structure beyond transcriptomic similarity alone. These results position LATTICE as a practical and empirically grounded framework for multimodal spatial omics integration, while also highlighting the need for stronger supervision and broader external benchmarking.
Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。