arXiv:2510.04315cs.CV2025-10被引 3

用自回归方法从染色图像预测基因表达,更准且符合生物实际。

GenAR: Next-Scale Autoregressive Generation for Spatial Gene Expression Prediction

  • 分层聚类基因,自回归逐个生成离散表达值,捕捉共表达关系。
  • 在4个组织数据集上优于现有方法,准确率显著提升。
  • 适合做低成本分子病理分析的研究者和临床转化团队。

空间转录组学(ST)提供基因表达的空间解析信息,但成本高昂。直接从广泛可用的苏木精-伊红(H&E)染色图像预测基因表达是一种更具成本效益的替代方案。然而,现有计算方法存在两个问题:(i) 独立预测每个基因,忽略基因间的共表达结构;(ii) 将任务视为连续回归,而表达实际为离散计数。这种不匹配会导致生物学上不合理的结果,并增加下游分析难度。我们提出GenAR,一种多尺度自回归框架,从粗到细逐步优化预测。GenAR通过层次聚类揭示基因间依赖关系,将表达建模为无码本的离散标记生成,直接预测原始计数,并融合组织学与空间嵌入进行解码。从信息论角度看,离散化避免了对数变换带来的偏差,粗到细的分解方式符合条件概率的合理分解。在四个不同组织类型的时空转录组数据集上的实验表明,GenAR达到当前最佳性能,为精准医疗和低成本分子谱型分析提供了潜在应用价值。代码已公开于 https://github.com/oyjr/genar。

原文摘要 · Abstract (English)

Spatial Transcriptomics (ST) offers spatially resolved gene expression but remains costly. Predicting expression directly from widely available Hematoxylin and Eosin (H&E) stained images presents a cost-effective alternative. However, most computational approaches (i) predict each gene independently, overlooking co-expression structure, and (ii) cast the task as continuous regression despite expression being discrete counts. This mismatch can yield biologically implausible outputs and complicate downstream analyses. We introduce GenAR, a multi-scale autoregressive framework that refines predictions from coarse to fine. GenAR clusters genes into hierarchical groups to expose cross-gene dependencies, models expression as codebook-free discrete token generation to directly predict raw counts, and conditions decoding on fused histological and spatial embeddings. From an information-theoretic perspective, the discrete formulation avoids log-induced biases and the coarse-to-fine factorization aligns with a principled conditional decomposition. Extensive experimental results on four Spatial Transcriptomics datasets across different tissue types demonstrate that GenAR achieves state-of-the-art performance, offering potential implications for precision medicine and cost-effective molecular profiling. Code is publicly available at https://github.com/oyjr/genar.

基因表达自回归空间转录组医学影像

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