University of Texas Health Science Center, Houston, TX, USA.
J Biomed Inform. 2012 Dec;45(6):1049-65. doi: 10.1016/j.jbi.2012.07.003. Epub 2012 Jul 26.
In this paper we utilize methods of hyperdimensional computing to mediate the identification of therapeutically useful connections for the purpose of literature-based discovery. Our approach, named Predication-based Semantic Indexing, is utilized to identify empirically sequences of relationships known as "discovery patterns", such as "drug x INHIBITS substance y, substance y CAUSES disease z" that link pharmaceutical substances to diseases they are known to treat. These sequences are derived from semantic predications extracted from the biomedical literature by the SemRep system, and subsequently utilized to direct the search for known treatments for a held out set of diseases. Rapid and efficient inference is accomplished through the application of geometric operators in PSI space, allowing for both the derivation of discovery patterns from a large set of known TREATS relationships, and the application of these discovered patterns to constrain search for therapeutic relationships at scale. Our results include the rediscovery of discovery patterns that have been constructed manually by other authors in previous research, as well as the discovery of a set of previously unrecognized patterns. The application of these patterns to direct search through PSI space results in better recovery of therapeutic relationships than is accomplished with models based on distributional statistics alone. These results demonstrate the utility of efficient approximate inference in geometric space as a means to identify therapeutic relationships, suggesting a role of these methods in drug repurposing efforts. In addition, the results provide strong support for the utility of the discovery pattern approach pioneered by Hristovski and his colleagues.
在本文中,我们利用超维计算方法来介导治疗性有用连接的识别,以实现基于文献的发现。我们的方法名为基于预测的语义索引,用于识别经验关系序列,称为“发现模式”,例如“药物 x 抑制物质 y,物质 y 导致疾病 z”,将药物物质与它们已知治疗的疾病联系起来。这些序列是由 SemRep 系统从生物医学文献中提取的语义谓词派生而来的,随后用于指导对一组保留疾病的已知治疗方法的搜索。通过在 PSI 空间中应用几何运算符,可以快速有效地进行推断,从而可以从大量已知的 TREATS 关系中推导出发现模式,并将这些发现的模式应用于大规模约束治疗关系的搜索。我们的结果包括重新发现了其他作者在之前的研究中手动构建的发现模式,以及发现了一组以前未被识别的模式。将这些模式应用于 PSI 空间中的直接搜索,比基于分布统计的模型更能恢复治疗关系。这些结果表明,在几何空间中进行高效近似推断是识别治疗关系的一种有效方法,表明这些方法在药物再利用方面具有一定的作用。此外,这些结果为 Hristovski 及其同事开创的发现模式方法的实用性提供了有力支持。