将高维细胞点云转为可解释的线性表示,实现精准分类与生成。
Linearized Optimal Transport for Analysis of High-Dimensional Point-Cloud and Single-Cell Data
- 用线性最优传输将不规则点云嵌入固定维度空间
- 在新冠患者分类中准确率高且可追溯关键生物标志物
- 适合需可解释性的单细胞数据分析与药物测试
单细胞技术产生高维细胞点云,能细致刻画复杂患者状态和治疗反应。但每位患者由不规则点云表示而非简单向量,难以直接量化和比较个体间生物差异。非线性方法如核函数和神经网络虽有预测精度,却缺乏生物学可解释性。为此,我们引入线性最优传输(LOT)框架,将不规则点云嵌入固定维欧氏空间,同时保留分布结构。该嵌入提供一种原则性的线性表示,保持最优传输几何,支持下游分析,并建立任意两名患者间的配准关系,实现细胞分布的直接比较。在此空间中,LOT实现:(i) 准确且可解释的新冠患者状态分类,分类器权重可映射至特定标记物和空间区域;(ii) 患者来源类器官的合成数据生成,利用LOT嵌入的线性特性。LOT重心生成平均细胞谱型,代表合并条件或样本,支持药物相互作用测试。这些结果确立了LOT作为统一框架,兼顾预测性能、可解释性与生成建模。通过将异构点云转化为可追溯原始数据的结构化嵌入,LOT为理解高维生物系统中的免疫变异与治疗效应开辟新路径。
原文摘要 · Abstract (English)
Single-cell technologies generate high-dimensional point clouds of cells, enabling detailed characterization of complex patient states and treatment responses. Yet each patient is represented by an irregular point cloud rather than a simple vector, making it difficult to directly quantify and compare biological differences between individuals. Nonlinear methods such as kernels and neural networks achieve predictive accuracy but act as black boxes, offering little biological interpretability. To address these limitations, we adapt the Linear Optimal Transport (LOT) framework to this setting, embedding irregular point clouds into a fixed-dimensional Euclidean space while preserving distributional structure. This embedding provides a principled linear representation that preserves optimal transport geometry while enabling downstream analysis. It also forms a registration between any two patients, enabling direct comparison of their cellular distributions. Within this space, LOT enables: (i) \textbf{accurate and interpretable classification} of COVID-19 patient states, where classifier weights map back to specific markers and spatial regions driving predictions; and (ii) \textbf{synthetic data generation} for patient-derived organoids, exploiting the linearity of the LOT embedding. LOT barycenters yield averaged cellular profiles representing combined conditions or samples, supporting drug interaction testing. Together, these results establish LOT as a unified framework that bridges predictive performance, interpretability, and generative modeling. By transforming heterogeneous point clouds into structured embeddings directly traceable to the original data, LOT opens new opportunities for understanding immune variation and treatment effects in high-dimensional biological systems.
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