用贝叶斯方法解析癌症染色体变异,发现共变模式。
A Bayesian Boolean Matrix Factorization with Application to Copy Number Analysis in Cancer

- 基于布尔逻辑的矩阵分解,自然捕捉染色体同步变化
- 在多发性骨髓瘤数据中识别出关键共扩增区域组合
- 提供可解释的潜在结构与不确定性量化,适合生物医学分析
二值数据分解常见,但传统实值方法忽略离散特性,难以解释。布尔矩阵分解(BooMF)通过逻辑与/或操作,将二值矩阵分解为两个低秩二值矩阵,以可解释的模式组合表达数据。在癌症基因组学中,该方法能揭示驱动肿瘤演化的协同特征变化,优于旋转或加性分解。现有方法多为启发式、依赖初始化、易陷入局部最优,且缺乏模型选择和不确定性量化。本文提出贝叶斯布尔矩阵分解(BBMF),一种全共轭生成模型,引入稀疏先验,强制满足布尔约束,获得可解释的潜在因子并实现不确定性量化,支持闭式吉布斯采样。由于癌症演化常伴随广泛、近同时的染色体数目变化(如全基因组复制后不稳定性与选择),布尔分解比加性模型更契合。应用于多发性骨髓瘤的臂级拷贝数改变数据(记录染色体臂扩增的存在/缺失),BBMF识别出少量可解释的双聚类,将患者亚群与反复共扩增染色体臂关联,提供肿瘤异质性的紧凑、生物学有意义的总结,证明了其在复杂二值数据中挖掘离散潜在结构的能力。
原文摘要 · Abstract (English)
Binary data factorization is common, but real-valued methods ignore discreteness and yield hard-to-interpret factors. Boolean Matrix Factorization (BooMF) instead decomposes a binary matrix into two lower-rank binary matrices via logical AND and OR, expressing the data as a Boolean disjunction of interpretable patterns. In cancer genomics, BooMF can reveal coordinated feature changes that may drive tumor evolution, unlike rotational or additive decompositions. Most existing BooMF methods are heuristic, greedy, sensitive to initialization, prone to local optima, and do not support principled model selection or uncertainty quantification. We introduce Bayesian Boolean Matrix Factorization (BBMF), a fully conjugate generative model with sparsity-inducing priors. It enforces Boolean constraints, yields interpretable latent factors with coherent uncertainty quantification, and admits Gibbs sampling with closed-form full conditionals. Because cancer evolution often involves widespread, near-simultaneous chromosome-number changes (e.g., whole-genome duplication followed by instability and selection), Boolean factorizations capture these patterns more naturally than additive models. Applied to arm-level copy-number alteration data in multiple myeloma, where entries indicate presence/absence of chromosomal-arm amplifications, BBMF finds a small set of interpretable bicliques linking patient subsets to recurrently co-altered chromosomal arms, providing a compact, biologically meaningful summary of tumor heterogeneity and demonstrating BBMF's utility for uncovering discrete latent structure in complex binary data.
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