Qabaja Ala, Jarada Tamer, Elsheikh Abdallah, Alhajj Reda
Department of Computer Science, University of Calgary, Calgary, Alberta, Canada.
J Bioinform Comput Biol. 2014 Jun;12(3):1450007. doi: 10.1142/S0219720014500073. Epub 2014 Mar 19.
The tremendous research effort on diseases and drug discovery has produced a huge amount of important biomedical information which is mostly hidden in the web. In addition, many databases have been created for the purpose of storing enormous amounts of information and high-throughput experiments related to drugs and diseases' effects on genes. Thus, developing an algorithm to integrate biological data from different sources forms one of the greatest challenges in the field of computational biology. Based on our belief that data integration would result in better understanding for the drug mode of action or the disease pathophysiology, we have developed a novel paradigm to integrate data from three major sources in order to predict novel therapeutic drug indications. Microarray data, biomedical text mining data, and gene interaction data have been all integrated to predict ranked lists of genes based on their relevance to a particular drug or disease molecular action. These ranked lists of genes have finally been used as a raw material for building a disease-drug connectivity map based on the enrichment between the up/down tags of a particular disease signature and the ranked lists of drugs. Using this paradigm, we have reported 13% sensitivity improvement in comparison with using microarray or text mining data independently. In addition, our paradigm is able to predict many clinically validated disease-drug associations that could not be captured using microarray or text mining data independently.
对疾病和药物发现的大量研究工作产生了大量重要的生物医学信息,这些信息大多隐藏在网络中。此外,为了存储与药物以及疾病对基因的影响相关的海量信息和高通量实验,已经创建了许多数据库。因此,开发一种算法来整合来自不同来源的生物数据成为计算生物学领域最大的挑战之一。基于我们的信念,即数据整合将有助于更好地理解药物作用模式或疾病病理生理学,我们开发了一种新颖的范式,以整合来自三个主要来源的数据,从而预测新的治疗药物适应症。微阵列数据、生物医学文本挖掘数据和基因相互作用数据都被整合起来,以根据基因与特定药物或疾病分子作用的相关性预测基因的排名列表。这些基因排名列表最终被用作构建疾病-药物连接图谱的原材料,该图谱基于特定疾病特征的上调/下调标签与药物排名列表之间的富集情况。使用这种范式,与单独使用微阵列或文本挖掘数据相比,我们报告的灵敏度提高了13%。此外,我们的范式能够预测许多独立使用微阵列或文本挖掘数据无法捕捉到的经过临床验证的疾病-药物关联。