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Experimental Biological Protocols with Formal Semantics

机译:具有形式语义学的实验生物学协议

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Both experimental and computational biology is becoming increasingly automated. Laboratory experiments are now performed automatically on high-throughput machinery, while computational models are synthesized or inferred automatically from data. However, integration between automated tasks in the process of biological discovery is still lacking, largely due to incompatible or missing formal representations. While theories are expressed formally as computational models, existing languages for encoding and automating experimental protocols often lack formal semantics. This makes it challenging to extract novel understanding by identifying when theory and experimental evidence disagree due to errors in the models or the protocols used to validate them. To address this, we formalize the syntax of a core protocol language, which provides a unified description for the models of biochemical systems being experimented on, together with the discrete events representing the liquid-handling steps of biological protocols. We present both a deterministic and a stochastic semantics to this language, both defined in terms of hybrid processes. In particular, the stochastic semantics captures uncertainties in equipment tolerances, making it a suitable tool for both experimental and computational biologists. We illustrate how the proposed protocol language can be used for automated verification and synthesis of laboratory experiments on case studies from the fields of chemistry and molecular programming.
机译:实验生物学和计算生物学都变得越来越自动化。现在,实验室实验是在高通量机器上自动执行的,而计算模型则是根据数据自动合成或推断的。然而,由于生物相容性的不兼容或缺少形式表示,生物发现过程中自动化任务之间仍然缺乏集成。尽管理论形式上以计算模型表示,但是用于编码和自动化实验协议的现有语言通常缺少形式语义。通过识别何时由于模型或用于验证它们的协议中的错误而导致理论和实验证据不一致时,很难提取新颖的理解。为了解决这个问题,我们对核心协议语言的语法进行了形式化,该语言为正在试验的生化系统的模型提供了统一的描述,并提供了代表生物协议液体处理步骤的离散事件。我们为这种语言提供了确定性语义和随机语义,均以混合过程的形式定义。特别是,随机语义捕获了设备公差中的不确定性,使其成为实验生物学家和计算生物学家的合适工具。我们将说明拟议的协议语言如何用于化学和分子程序设计领域中案例研究的自动验证和实验室实验综合。

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