Department of Bioengineering, University of California San Diego, La Jolla, CA 92093.
Quantitative BioSciences, Inc., San Diego, CA 92121.
Proc Natl Acad Sci U S A. 2020 Feb 11;117(6):3301-3306. doi: 10.1073/pnas.1913003117. Epub 2020 Jan 23.
Genome-scale technologies have enabled mapping of the complex molecular networks that govern cellular behavior. An emerging theme in the analyses of these networks is that cells use many layers of regulatory feedback to constantly assess and precisely react to their environment. The importance of complex feedback in controlling the real-time response to external stimuli has led to a need for the next generation of cell-based technologies that enable both the collection and analysis of high-throughput temporal data. Toward this end, we have developed a microfluidic platform capable of monitoring temporal gene expression from over 2,000 promoters. By coupling the "Dynomics" platform with deep neural network (DNN) and associated explainable artificial intelligence (XAI) algorithms, we show how machine learning can be harnessed to assess patterns in transcriptional data on a genome scale and identify which genes contribute to these patterns. Furthermore, we demonstrate the utility of the Dynomics platform as a field-deployable real-time biosensor through prediction of the presence of heavy metals in urban water and mine spill samples, based on the the dynamic transcription profiles of 1,807 unique promoters.
基因组规模的技术使绘制控制细胞行为的复杂分子网络成为可能。在对这些网络进行分析时,一个新出现的主题是,细胞使用多层次的调节反馈来不断评估和精确响应其环境。复杂反馈在控制对外界刺激的实时响应中的重要性,导致需要新一代基于细胞的技术,这些技术能够同时收集和分析高通量的时间数据。为此,我们开发了一种能够监测来自 2000 多个启动子的时间基因表达的微流控平台。通过将“Dynomics”平台与深度神经网络(DNN)和相关的可解释人工智能(XAI)算法相结合,我们展示了如何利用机器学习来评估基因组范围内转录数据中的模式,并确定哪些基因对这些模式有贡献。此外,我们通过基于 1807 个独特启动子的动态转录谱,展示了 Dynomics 平台作为一种可现场部署的实时生物传感器的实用性,用于预测城市水和矿场溢流水样中重金属的存在。