用生物通路图增强分类,提升小样本组学数据的预测可靠性
Structured Gaussian Processes for Uncertainty-Aware Classification of High-Dimensional, Small-Sampled Omics Data

- 将已知生物通路嵌入核函数,融合表达量与网络拓扑信息
- 在三个肠道微生物组数据集上,少数类准确率显著优于基线方法
- 输出概率化不确定性,帮助识别可信与模糊样本
高维小样本组学数据的分类仍是计算生物学中的核心挑战,尤其在非线性交互主导且类别不平衡的场景下,少数表型的可靠预测尤为困难。传统核方法依赖特征丰度,却未能利用已知的生物系统互作图谱。本文提出一种结构化高斯过程分类框架,将图编码的生物通路直接融入核函数构建。通过沿已知互作网络传播信息,并结合丰度特征,新模型同时捕捉定量测量与拓扑上下文。我们在三个公开的肠道及粪便微生物组数据集上进行基准测试。为应对严重类别不平衡,评估了数据重采样、阈值校准和混淆矩阵调整等策略,并报告少数类性能与整体准确率。混合方法相较无结构基线有性能提升,且达到同类数据集现有基准水平。此外,该框架的概率特性天然提供校准后的预测不确定性,可有效区分确定性预测与模糊样本。
原文摘要 · Abstract (English)
Classifying heterogeneous omics data remains a fundamental challenge in computational biology, particularly in high-dimensional, small-sample settings where nonlinear interactions dominate and class imbalance further complicates reliable prediction of minority phenotypes. While traditional kernel methods rely on feature abundance, they fail to leverage the known interaction landscapes of biological systems. In this work, we propose a structured Gaussian process classification framework that integrates graph-encoded biological pathways directly into the kernel construction. By propagating information along known interaction networks and combining this with abundance-derived features, the resulting classifier captures both quantitative measurements and topological context. We benchmark our proposed methodology on three publicly available gut and fecal microbiome datasets. To address severe class imbalance, we evaluate complementary strategies, including data-level resampling, threshold calibration, and confusion-matrix-based adjustments, and report minority-class performance alongside accuracy. The hybrid approach yields a performance gain over unstructured baselines and matches the performance of established benchmarks for similar datasets. Furthermore, the probabilistic nature of the framework naturally provides calibrated predictive uncertainty, enabling robust differentiation between confident predictions and ambiguous samples.
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