解决大规模细胞成像数据的批次效应问题,提升药物筛选准确性。
Scalable Batch Correction for Cell Painting via Batch-Dependent Kernels and Adaptive Sampling
- 用局部自适应核函数建模样本间亲和关系,捕捉批次差异。
- 通过自适应采样仅保留关键亲和关系,计算效率接近线性增长。
- 在真实与合成数据上均表现优越,适合超大规模生物图像分析。
Cell Painting 是一种基于显微镜的高内涵成像检测方法,可生成细胞丰富的形态学特征,支持药物发现中对化学扰动的细胞响应量化。然而在大规模应用中,由于实验室、仪器和流程差异,数据受显著批次效应影响,掩盖生物信号。本文提出 BALANS(基于局部亲和力与子采样的批次对齐方法),通过构建平滑亲和矩阵实现跨批次样本对齐。给定 n 个数据点,BALANS 构造稀疏亲和矩阵 A ∈ ℝ^{n×n}:(i) 对点 i 与 j,使用点 i 到 j 批次中第 k 近邻的距离作为局部尺度,以该尺度校准高斯核计算 A_{ij};(ii) 不构建全部 n² 条目,而是采用自适应采样策略,优先选择邻居覆盖度低的行,并保留每行最强亲和关系,从而获得稀疏但信息丰富的近似矩阵。我们证明该采样策略在样本复杂度上为最优,并提供逼近保证,且 BALANS 运行时间接近 O(n)。在多种真实世界 Cell Painting 数据集和可控的大规模合成基准上的实验表明,BALANS 可扩展至大规模数据集,在保持校正质量的同时,运行速度显著优于主流批次校正方法的原生实现。
原文摘要 · Abstract (English)
Cell Painting is a microscopy-based, high-content imaging assay that produces rich morphological profiles of cells and can support drug discovery by quantifying cellular responses to chemical perturbations. At scale, however, Cell Painting data is strongly affected by batch effects arising from differences in laboratories, instruments, and protocols, which can obscure biological signal. We present BALANS (Batch Alignment via Local Affinities and Subsampling), a scalable batch-correction method that aligns samples across batches by constructing a smoothed affinity matrix from pairwise distances. Given $n$ data points, BALANS builds a sparse affinity matrix $A \in \mathbb{R}^{n \times n}$ using two ideas. (i) For points $i$ and $j$, it sets a local scale using the distance from $i$ to its $k$-th nearest neighbor within the batch of $j$, then computes $A_{ij}$ via a Gaussian kernel calibrated by these batch-aware local scales. (ii) Rather than forming all $n^2$ entries, BALANS uses an adaptive sampling procedure that prioritizes rows with low cumulative neighbor coverage and retains only the strongest affinities per row, yielding a sparse but informative approximation of $A$. We prove that this sampling strategy is order-optimal in sample complexity and provides an approximation guarantee, and we show that BALANS runs in nearly linear time in $n$. Experiments on diverse real-world Cell Painting datasets and controlled large-scale synthetic benchmarks demonstrate that BALANS scales to large collections while improving runtime over native implementations of widely used batch-correction methods, without sacrificing correction quality.
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