PO.BCS01.10 · 生物信息与计算
OncoGraphDB:对患者层面多模态图数据库进行快速投影,促进肿瘤亚型的高效探索,并识别患者预后与基因必需性的新型组合生物标志物
OncoGraphDB: Rapid projections of patient-level multimodal graph database facilitates efficient exploration of tumor subtypes and identifies new combinatorial biomarkers of patient outcomes and gene essentiality
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
癌症组学数据往往被孤立分析,而忽略了其他相关数据模态,尽管在分析多模态模型时可能带来额外获益。一种策略是纳入所有可用数据,但如果模型中存在对分析没有显著贡献的数据模态,这种方法可能会掩盖潜在信号。为实现对多模态数据的高效探索,我们开发了OncoGraphDB框架,可从一个更大的、全面包容的癌症组学知识图谱中快速投影出子图。这使我们能够利用用户自定义的指标(即患者生存、药物反应或预测的基因必需性)来识别可最大程度区分目标患者的子空间。我们发现,在各种癌症适应证中,基因表达数据提供了最多的单模态信息,这与近期发表的几项研究结果一致。然而,当在分析中纳入额外的数据模态(包括体细胞突变特征和DNA甲基化谱)时,预测预后和共享基因必需性评分的性能得到了提升。随后,我们将智能体AI应用于Neo4j图框架,以支持对癌症组学知识图谱的交互式查询,为领域专家提供用于假设生成的探索性数据门户。最后,我们描述了用于将新患者样本投影到图上的基因表达和图像分类器,以支持N-of-1逆向转化研究。OncoGraphDB平台促进了对复杂癌症数据库的高效探索,并为精准医学应用提供数据分析解决方案。
所有作者均曾经或现在是AbbVie的雇员。本研究的设计、研究实施和资金支持均由AbbVie提供。AbbVie参与了数据解释、出版物审阅和批准。未因署名支付任何酬金或款项。
查看英文原文 English abstract
Cancer ‘omics data are often analyzed in isolation of other related data modalities despite the potential for added benefit when analyzing a multimodal model. One strategy is to include all available data, but this approach may obfuscate the underlying signal if data modalities exist in the model that do not significantly contribute to the analysis. To enable efficient exploration of multimodal data, we developed the OncoGraphDB framework to rapidly project subgraphs of a larger, all inclusive, cancer omics knowledge graph. This enabled us to identify subspaces that maximally separate patients of interest using a user-defined metric (i.e. patient survival, drug response, or predicted gene essentiality). We found that across cancer indications, gene expression data provided the most single-mode information, which is consistent with several recently published studies. However, performance was improved when predicting prognosis and shared gene essentiality scores when additional data modalities were included in the analysis, including somatic mutation signatures and DNA methylation profiles. Agentic AI was then applied to the Neo4j graph framework to support interactive interrogation of the cancer -omics knowledge graph providing domain experts an exploratory data portal for hypothesis generation. Finally, we describe the gene expression and image classifiers for projecting new patient samples onto the graph to support N-of-1 reverse translation studies. The OncographDB platform facilitates efficient exploration of complex cancer databases and provides data analysis solutions for precision medicine applications.
All Authors were or are employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication. No honoraria or payments were made for authorship.
利益披露 Disclosure
J. Pfeil,
AbbVie Inc. Employment.
A. Tse,
AbbVie Inc. Employment.
S. Villarruel,
AbbVie Inc. Employment.
E. Rossi,
AbbVie Inc. Employment.
L. Ma,
AbbVie Inc. Employment.
X. Zhao,
AbbVie Inc. Employment.
J. Samayoa,
AbbVie Inc. Employment.
K. Halliwill,
AbbVie Inc. Employment.