Wren Jonathan D, Bekeredjian Raffi, Stewart Jelena A, Shohet Ralph V, Garner Harold R
Advanced Center for Genome Technology, Department of Botany and Microbiology, The University of Oklahoma, 620 Parrington Oval Rm. 106, Norman, OK 73019, USA.
Bioinformatics. 2004 Feb 12;20(3):389-98. doi: 10.1093/bioinformatics/btg421. Epub 2004 Jan 22.
New relationships are often implicit from existing information, but the amount and growth of published literature limits the scope of analysis an individual can accomplish. Our goal was to develop and test a computational method to identify relationships within scientific reports, such that large sets of relationships between unrelated items could be sought out and statistically ranked for their potential relevance as a set.
We first construct a network of tentative relationships between 'objects' of biomedical research interest (e.g. genes, diseases, phenotypes, chemicals) by identifying their co-occurrences within all electronically available MEDLINE records. Relationships shared by two unrelated objects are then ranked against a random network model to estimate the statistical significance of any given grouping. When compared against known relationships, we find that this ranking correlates with both the probability and frequency of object co-occurrence, demonstrating the method is well suited to discover novel relationships based upon existing shared relationships. To test this, we identified compounds whose shared relationships predicted they might affect the development and/or progression of cardiac hypertrophy. When laboratory tests were performed in a rodent model, chlorpromazine was found to reduce the progression of cardiac hypertrophy.
新的关系往往隐含于现有信息之中,但已发表文献的数量和增长限制了个人能够完成的分析范围。我们的目标是开发并测试一种计算方法,以识别科学报告中的关系,从而能够找出大量无关项目之间的关系集,并根据其潜在相关性进行统计排序。
我们首先通过识别生物医学研究感兴趣的“对象”(如基因、疾病、表型、化学物质)在所有电子可用的MEDLINE记录中的共现情况,构建一个初步关系网络。然后,将两个不相关对象共享的关系与随机网络模型进行比较,以估计任何给定分组的统计显著性。与已知关系相比,我们发现这种排序与对象共现的概率和频率相关,表明该方法非常适合基于现有共享关系发现新的关系。为了验证这一点,我们识别出其共享关系预测可能影响心肌肥大发展和/或进展的化合物。在啮齿动物模型中进行实验室测试时,发现氯丙嗪可减缓心肌肥大的进展。