arXiv:2607.18602cs.LG2026-07被引 1

提出新框架,精准识别基因协同调控组合并定位失败原因。

BRIDGE: Bottleneck-Aware Regulator-Set Inference and Diagnosis for Cooperative Gene Regulatory Recovery

论文配图:BRIDGE: Bottleneck-Aware Regulator-Set Inference and Diagnosis for Cooperative Gene Regulatory Recovery
图 1 · 摘自论文原文
  • 基于残差高阶评分,直接从表达数据恢复协同调控集
  • 在30组设定中提升召回率至59.7%,精确恢复率翻倍至11.3%
  • 可区分排序、检索、评分等不同阶段的错误,适合系统性分析者

协同基因调控常依赖多个调控因子共同作用,但现有基因调控网络推断方法仅输出成对调控关系。本文提出BRIDGE框架,实现完整调控集恢复,并引入TRACE诊断工具,将失败归因于检索、集评分、解码和评估等瓶颈。其中,无泄漏机制错配协同学压力测试采用随机非线性机制生成协同目标,避免特征-机制循环。残差高阶评分(Residual HOS2)直接作用于原始表达向量,无需手工构造乘积相关特征。在30组匹配种子协同学设置下,相比可分解成对集评分器(PairS2),Residual HOS2将杰卡德相似度从0.382提升至0.460,召回率从0.522增至0.597,精确恢复率从0.053升至0.113,尽管精确恢复仍低。在SERGIO DS3上,真值检索与TRACE分析表明候选覆盖必要但不足,集评分错误仍是精确恢复失败主因。以PairS2提议后经Residual HOS2重排序,使HOS2评分候选集减少94%-97%,同时基本保留精确恢复行为。结果明确区分了边排序、候选检索、集评分与精确协同调控集恢复为不同目标。

原文摘要 · Abstract (English)

Cooperative gene regulation often depends on groups of regulators acting jointly, but most gene regulatory network (GRN) inference methods output pairwise regulator-target rankings. We introduce Bottleneck-Aware Regulator-Set Inference and Diagnosis (BRIDGE), a framework for complete regulator-set recovery, and Targeted Recovery Attribution for Cooperative Evaluation (TRACE), a diagnostic suite that attributes failures to retrieval, set-level scoring, decoding, and evaluation bottlenecks. TRACE includes a leak-free mechanism-mismatch cooperativity stress test in which cooperative targets are generated by random nonlinear mechanisms rather than product interactions. This design avoids feature-mechanism circularity: Residual higher-order set scoring (Residual HOS2) operates on raw expression vectors without handcrafted product-correlation features. Across 30 matched seed-cooperativity settings, Residual HOS2 improves Jaccard similarity from 0.382 to 0.460, recall from 0.522 to 0.597, and exact recovery from 0.053 to 0.113 over a decomposable pairwise set scorer (PairS2), although exact recovery remains low. On SERGIO DS3, oracle retrieval and TRACE show that candidate coverage is necessary but insufficient because set-level misranking remains the dominant source of exact-recovery failure. PairS2 proposal followed by Residual HOS2 reranking reduces HOS2-scored candidate sets by 94-97% while largely preserving exact-recovery behavior. These results distinguish edge ranking, candidate retrieval, set-level scoring, and exact cooperative regulator-set recovery as separate objectives.

基因调控协同作用网络推断诊断框架

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