论文标题

通过知识图挖掘和可解释的AI研究ADR机制

Investigating ADR mechanisms with knowledge graph mining and explainable AI

论文作者

Bresso, Emmanuel, Monnin, Pierre, Bousquet, Cédric, Calvier, François-Elie, Ndiaye, Ndeye-Coumba, Petitpain, Nadine, Smaïl-Tabbone, Malika, Coulet, Adrien

论文摘要

不良药物反应(ADR)是在随机临床试验和市场后药物守护中表征的,但在大多数情况下,它们的分子机制仍然未知。除临床试验外,在开放式知识图中还可以使用许多有关药物成分知识的要素。此外,已经建立了将药物标记为病因或不为几种ADR的药物分类。我们建议挖掘知识图,以识别可能使自动分类的生物分子特征自动分类,从而区分给定类型的ADR药物导致或不区分药物的原因。从可解释的AI角度来看,我们探讨了简单的分类技术,例如决策树和分类规则,因为它们提供了可读的模型,这些模型可以解释分类本身,但也可能提供有关ADR背后分子机制的解释元素。总而言之,我们为特征挖了知识图。我们培训分类器,以区分与ADR相关的药物;我们隔离了在重现专家分类和由专家(即基因本体术语,药物靶标或途径名称)中解释的特征;我们手动评估它们如何解释。提取的特征以良好的忠诚度分类为dili和疤痕而繁殖。专家完全同意,最歧视性的73%和38%的特征可能分别解释了Dili和Scar。并部分同意(2/3),其中90%和77%。知识图提供了各种特征,以启用简单和可解释的模型,以区分ADR或不为ADR的药物区分。除了解释分类外,大多数判别特征似乎是进一步研究ADR机制的好候选者。

Adverse Drug Reactions (ADRs) are characterized within randomized clinical trials and postmarketing pharmacovigilance, but their molecular mechanism remains unknown in most cases. Aside from clinical trials, many elements of knowledge about drug ingredients are available in open-access knowledge graphs. In addition, drug classifications that label drugs as either causative or not for several ADRs, have been established. We propose to mine knowledge graphs for identifying biomolecular features that may enable reproducing automatically expert classifications that distinguish drug causative or not for a given type of ADR. In an explainable AI perspective, we explore simple classification techniques such as Decision Trees and Classification Rules because they provide human-readable models, which explain the classification itself, but may also provide elements of explanation for molecular mechanisms behind ADRs. In summary, we mine a knowledge graph for features; we train classifiers at distinguishing, drugs associated or not with ADRs; we isolate features that are both efficient in reproducing expert classifications and interpretable by experts (i.e., Gene Ontology terms, drug targets, or pathway names); and we manually evaluate how they may be explanatory. Extracted features reproduce with a good fidelity classifications of drugs causative or not for DILI and SCAR. Experts fully agreed that 73% and 38% of the most discriminative features are possibly explanatory for DILI and SCAR, respectively; and partially agreed (2/3) for 90% and 77% of them. Knowledge graphs provide diverse features to enable simple and explainable models to distinguish between drugs that are causative or not for ADRs. In addition to explaining classifications, most discriminative features appear to be good candidates for investigating ADR mechanisms further.

扫码加入交流群

加入微信交流群

微信交流群二维码

扫码加入学术交流群,获取更多资源