IEEE/ACM Trans Comput Biol Bioinform. 2019 May-Jun;16(3):1029-1035. doi: 10.1109/TCBB.2018.2841396. Epub 2018 May 29.
Likely drug candidates which are identified in traditional pre-clinical drug screens often fail in patient trials, increasing the societal burden of drug discovery. A major contributing factor to this phenomenon is the failure of traditional in vitro models of drug response to accurately mimic many of the more complex properties of human biology. We have recently introduced a new microphysiological system for growing vascularized, perfused microtissues that more accurately models human physiology and is suitable for large drug screens. In this work, we develop a machine learning model that can quickly and accurately flag compounds which effectively disrupt vascular networks from images taken before and after drug application in vitro. The system is based on a convolutional neural network and achieves near perfect accuracy while committing potentially no expensive false negatives.
在传统的临床前药物筛选中发现的可能药物候选物在患者试验中往往会失败,这增加了药物发现的社会负担。造成这种现象的一个主要因素是传统的体外药物反应模型无法准确模拟人类生物学的许多更复杂特性。我们最近引入了一种新的微生理系统,用于生长血管化、灌注的微组织,该系统更准确地模拟了人类生理学,适合进行大型药物筛选。在这项工作中,我们开发了一种机器学习模型,可以快速准确地标记出在体外药物应用前后拍摄的图像中有效破坏血管网络的化合物。该系统基于卷积神经网络,实现了近乎完美的准确性,同时不会产生昂贵的假阴性。