PO.BCS01.12 · 生物信息与计算
NetFlow 框架中的多模态整合,用于全面的探索性数据分析
Multi-modal integration in the NetFlow framework for comprehensive exploratory data analysis
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
高维生物医学研究日益需要全面的探索性工具,以在单一、可解释的框架内联合建模、整合并可视化跨模态的样本组织结构。为此,我们开发了 NetFlow,这是一个计算框架,可从高维和多模态数据中构建样本关系的伪组织结构(Pseudo-Organizational StructurE,POSE)图,在保留连续变异和局部邻域的同时,实现在同一空间中的下游分析。胶质母细胞瘤(GBM)在转录组、表观基因组和 miRNA 图谱上表现出显著的异质性,使亚型发现和解释变得复杂。为展示 NetFlow 的多模态整合能力,我们将其应用于 TCGA GBM(n=213),并配有匹配的 mRNA 表达、DNA 甲基化和 miRNA 图谱。计算了各模态的样本-样本距离,将每个模态转换到共同的范围,然后融合为统一的相似性矩阵。接着,基于扩散的多尺度度量在融合的相似性上为受谱系追踪启发的骨架提供种子,并辅以互近邻边来构建 POSE。NetFlow 框架实现了 POSE 感知的聚类、生存分析和跨组学差异特征检验。POSE 揭示了一个独特的低风险 GBM 亚组,其总生存期显著改善(log-rank P=1.19×10⁻⁵),而这一发现无法从任何单一模态中单独重现。该亚组表现出跨组学特征,包括 EMP3 和 TIMP1 的 mRNA 表达降低、CRIP1 高甲基化以及 miR-222 表达下降。此外,所识别的亚组显示出与良好预后一致的临床相关性,包括 IDH1 突变富集和更年轻的年龄。我们进一步量化了边级别的模态影响,结果表明各模态贡献均衡,支持真正的多模态整合而非任何单一数据类型的主导。这些结果确立了 NetFlow 能产生可解释、模态均衡的 POSE。它们进一步表明,其统一的建模、整合、可视化和分析能够发现具有预后相关性的亚组和跨组学生物标志物。更广泛而言,NetFlow 为多模态肿瘤学队列中的全面探索性数据分析提供了一个实用、可扩展的框架,其应用可推广至 GBM 之外,在多样化的场景中加速假设生成和亚型细化。
查看英文原文 English abstract
High-dimensional biomedical studies increasingly require comprehensive exploratory tools that jointly model, integrate, and visualize sample organization across modalities within a single, interpretable framework. We therefore developed NetFlow, a computational framework that constructs a Pseudo-Organizational StructurE (POSE) graph of sample relationships from high-dimensional and multimodal data, preserving both continuous variation and local neighborhoods while enabling downstream analytics in the same space. Glioblastoma (GBM) exhibits pronounced heterogeneity across transcriptomic, epigenomic, and miRNA profiles that complicates subtype discovery and interpretation. To demonstrate NetFlow's multi-modal integration capability, we applied it to TCGA GBM (n=213) with matched mRNA expression, DNA methylation, and miRNA profiles. Per-modality sample-sample distances were computed, each was transformed to a common range, and then fused into a unified similarity matrix. Next, diffusion-based, multi-scale metrics on the fused similarity seeded a lineage-tracing-inspired backbone augmented with mutual nearest neighbor edges to build the POSE. The NetFlow framework enabled POSE-aware clustering, survival analysis, and cross-omic differential feature testing. The POSE revealed a distinct lower-risk GBM subgroup with significantly improved overall survival (log-rank P=1.19x10 -5 ) that was not reproducible from any single modality alone. This subgroup exhibited a cross-omic signature including reduced mRNA expression of EMP3 and TIMP1 , CRIP1 hypermethylation, and decreased miR-222 expression. Additionally, the identified subgroup showed clinical correlates consistent with favorable prognosis including enrichment for IDH1 mutation and younger age. We further quantified edge-level modality influence, which indicated balanced contributions from each modality, supporting genuine multi-modal integration rather than dominance by any single data type. These results establish that NetFlow yields an interpretable, modality-balanced POSE. They further demonstrate that its unified modeling, integration, visualization, and analysis enables discovery of prognostically relevant subgroups and cross-omic biomarkers. More broadly, NetFlow provides a practical, extensible framework for comprehensive exploratory data analysis in multi-modal oncology cohorts that generalizes beyond GBM to accelerate hypothesis generation and subtype refinement in diverse settings.
利益披露 Disclosure
R. Elkin, None..
A. K. Simhal, None..
J. O. Deasy, None.