用测试时训练层融合单细胞基因与蛋白数据,提升多组学分析精度。
scFusionTTT: Single-cell transcriptomics and proteomics fusion with Test-Time Training layers
- 引入测试时训练层建模基因/蛋白序列顺序关系
- 在四组多组学与四组单组学数据上表现最优
- 适合研究肿瘤异质性与靶向治疗的生物信息学者
单细胞多组学(scMulti-omics)指通过如CITE-seq等技术获取的基因与蛋白配对数据,可揭示肿瘤内部异质性并理解不同细胞类型的遗传特性,对靶向治疗至关重要。当前基于注意力机制的深度学习方法面临两大挑战:一是单细胞中基因数量庞大,传统注意力模块受限于长序列建模能力与高复杂度计算;二是人类基因组中基因具有顺序排列且相互影响,多数方法忽略此序列信息。近期提出的测试时训练(TTT)层是一种线性复杂度序列建模结构,特别适合处理基因组这类长序列数据。本文提出scFusionTTT,一种基于TTT的掩码自编码器方法,融合基因与蛋白的基因组顺序信息,实现多组学数据融合与单组学分析增强。模型采用三阶段训练策略,在四个多组学数据集和四个单组学数据集上均取得最佳性能。代码与数据将开源于https://github.com/DM0815/scFusionTTT。
原文摘要 · Abstract (English)
Single-cell multi-omics (scMulti-omics) refers to the paired multimodal data, such as Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), where the regulation of each cell was measured from different modalities, i.e. genes and proteins. scMulti-omics can reveal heterogeneity inside tumors and understand the distinct genetic properties of diverse cell types, which is crucial to targeted therapy. Currently, deep learning methods based on attention structures in the bioinformatics area face two challenges. The first challenge is the vast number of genes in a single cell. Traditional attention-based modules struggled to effectively leverage all gene information due to their limited capacity for long-context learning and high-complexity computing. The second challenge is that genes in the human genome are ordered and influence each other's expression. Most of the methods ignored this sequential information. The recently introduced Test-Time Training (TTT) layer is a novel sequence modeling approach, particularly suitable for handling long contexts like genomics data because TTT layer is a linear complexity sequence modeling structure and is better suited to data with sequential relationships. In this paper, we propose scFusionTTT, a novel method for Single-Cell multimodal omics Fusion with TTT-based masked autoencoder. Of note, we combine the order information of genes and proteins in the human genome with the TTT layer, fuse multimodal omics, and enhance unimodal omics analysis. Finally, the model employs a three-stage training strategy, which yielded the best performance across most metrics in four multimodal omics datasets and four unimodal omics datasets, demonstrating the superior performance of our model. The dataset and code will be available on https://github.com/DM0815/scFusionTTT.
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。