Artificial Intelligence Tools For Automatic Single Molecule Analysis

*我们将做什么？*开发和分发一种“人工智能”应用程序，允许科学家同事分析一种用现有方法难以分析的数据类型(“单分子数据”)。*机器可以学习，但需要大量培训*机器可以识别设备中的语音，从亚马逊的Alexa到使用人工智能(AI)的呼叫中心。举个例子，只要问Alexa什么是“AI”，她就会告诉你。直到最近，随着计算机变得足够强大，这才成为可能。实现这一目标的技术统称为“机器学习”。这种“机器”的一个优点是，它们可以在没有人监督的情况下回答问题。其中一个限制是，它们首先需要大量标记的数据集才能“学习”。这被称为“训练数据”。我们设计了一个生成海量数据集的“技巧”，通过将模拟数据播放到记录设备中，然后再将生成的信号记录下来。因为我们控制着整个过程，所以数据本身就被贴上了训练智能机器所必需的标签。有了这项技术，再加上谷歌大脑免费提供的“TensorFlow”人工智能库，我们就可以创建为我们分析数据的应用程序。*为什么是“单分子”*动物细胞中发现的许多分子都是开关。它们各自的“开”或“关”状态可以通过光脉冲或电流来测量，从而提供实时的机械洞察。它们在整个生物学领域都很重要，仅针对其中一类分子开关(离子通道)的全球药物市场估计就达到115亿美元。另一方面，测量这些“开关”的实验产生的大数据集分析起来既困难又费力。*单分子生物学是否有助于应对老年病、气候变化、抗菌素耐药性和全球恐怖主义？*简而言之，“是的”：离子通道故障尤其是导致许多与年龄相关的疾病的原因。Pharma的兴趣是巨大的，因为从镇静剂到心脏药物，它们是许多药物的靶标。某些杀虫剂通过它们的离子通道起作用，但这些对人也是有毒的。其中一种毒剂是神经毒素“VX”，它被用于刺杀金正男时登上了新闻头条。即使是相对安全的驱蚊剂香茅也通过激活离子通道来驱赶蚊子。抗氯氰菊酯的蚊子之所以具有抗药性，是因为它们在离子通道中有一种特殊的突变，这在疟疾控制中造成了真正的问题。植物也表达一系列具有关键作用的离子通道，包括盐调节。由于气候变化正在加剧许多农业区的盐碱化，人们对根离子通道的生物修饰是否能够促进作物在富盐土壤中的生存产生了浓厚的兴趣。离子通道在合成生物学中也被研究过，因为它们可以被浓度远低于其他传感器的化学物质激活。已提议将其用于许多用途，例如检测爆炸物、生物武器、毒品或某些疾病。最近的一项发现是，细菌还通过依赖于离子通道的生物膜通讯网络相互“交谈”，这是它们生存所必需的。这增加了离子通道阻断药物可能构成新一代抗菌药的可能性，这些抗菌药对耐药性不那么敏感。因此，单分子生物学确实可以为研究社会中的几个重大挑战做出贡献。在每种情况下，一个限制因素是目前研究这些分子产生的大型数据集所需的时间。*我们能提供什么帮助？*我们将创建一个简单易用的基于人工智能的分析应用程序，以实现对这些数据的快速分析。对于那些在药物开发期间产生大量数据集，但几乎没有可用的工具来全面分析这一点的工业合作伙伴来说，这些将特别有用。

*What will we do?*Develop and distribute an "artificial intelligence" application to allow fellow scientists to analyze a type of data ("single molecule data") difficult to analyse with existing methods. *Machines can learn, but they take a lot of training*Machines can recognise speech in devices from Amazon's "Alexa" to call centres using artificial intelligence ("AI"). As an example, just ask Alexa what "AI" is, and she will tell you. This has only been possible recently as computers have become sufficiently powerful. The technologies to do it are collectively called "machine learning". One advantage of such "machines" is that they can answer questions unsupervised by people. One limitation is that they require enormous labelled datasets to "learn" in the first place. This is called "training data". We have devised, a "trick" to generate massive datasets, by playing simulated data into recording apparatus and then recording back the resulting signal. Because we control the entire process the data is inherently "labelled" in the way necessary to train intelligent machines. With this technique together with the use of Google Brain's freely available "TensorFlow" AI library, we can create applications that analyze data for us.*Why "Single Molecules"*Many molecules found in animal cells behave as switches. Their individual "on" or "off" state can then be measured as either pulses of light or electrical current giving real-time mechanistic insight. They are important throughout biology with the estimated Global market for drugs targeting one family of these molecular switches (ion channels) alone being $11.5bn. The flip-side is that experiments measuring these "switches" generate big datasets that are difficult and laborious to analyse.*Could single molecule biology contribute to tackling diseases of age, climate change, anti-bacterial resistance and global terrorism?*In short "Yes": Ion channel malfunction in particular, is responsible for many age-related diseases. Interest from Pharma is enormous because they are targets for many drugs from sedatives to heart medicines. Certain insecticides act via their ion channels, but these are toxic to people too. One such agent, the nerve toxin "VX" hit the news when it was used in the assassination of Kim Jong-Nam. Even the relatively safe insect repellent citronella repels mosquitoes by activating ion channels. Permethrin-resistant mosquitoes are resistant because they have a specific mutation in an ion channel creating a real problem in malaria control. Plants too express a range of ion channels with critical roles including salt regulation. Since climate change is increasing the salination of many agricultural regions, there is keen interest in whether biological modification of root ion channels could promote survival of crops in salt-rich soils. Ion channels have also been studied in synthetic biology because they can be activated by chemicals at concentrations far lower than that of other sensors. Many uses have been proposed for these, such as detection of explosives, biological weapons, narcotics or certain diseases. A recent discovery is that bacteria also "talk" to each other by an ion channel dependent biofilm communication network that is necessary for their survival. This has raised the possibility that ion channel blocking drugs could constitute a new generation of antibacterials that are less susceptible to resistance. So indeed single molecule biology could contribute to study of several grand challenges in society. In each case, a limiting factor is currently the time required to study the large datasets generated by these molecules. *How can we help?*We will create a simple to use AI-based analysis application to allow rapid analysis of these data. These will be especially useful to industrial partners who produce large data sets during drug development but have few tools available to analyze this fully.