Towards full sequence design of functional chromosomes by AI

目前合成基因组学的进展意味着我们设计和构建DNA的规模正在迅速增加。与此同时，支持人工智能的工具正在加速我们的能力，以设计遗传编码的部件，以实现所需的规格。因此，我们应该期待“未来的生物设计师”使用人工智能来帮助编写定制的DNA序列，这些DNA序列可以组装成完整的染色体和基因组，驱动细胞执行所需的任务。在这个项目中，我们计划看看我们已经多么接近人工智能领导的合成酵母染色体的全序列设计。在设计、构建和测试酵母染色体的人工智能写入区域时，我们将了解目前缺少哪些基因组知识和人工智能设计能力，以便在未来十年进行定制的染色体设计。我们计划为这些目前的差距开发解决方案，以便在项目结束时，我们可以使用人工智能来生成合成染色体臂的完整序列，为人工智能提供仅包括的基因列表、这些基因的肽序列、它们的目标表达水平以及它们所需的任何调节。该项目将利用我们两个研究小组在构建和测试酵母合成染色体区域(Ellis)以及设计人工智能驱动的工程生物学工具(STAN)方面的现有工作。重要的是，它将建立在已发表的关键人工智能工具的现有成功的基础上，这些工具使用GAN和CNN来编写合成酵母启动子[1]、5‘UTRs[2]和3’UTRs[3]来具体说明。这3个遗传部分加在一起占酵母染色体中非编码DNA的85%

Current progress in synthetic genomics means that the scale at which we design and build DNA israpidly increasing. In parallel, AI-enabled tools are accelerating our capabilities to designgenetically-encoded parts to achieve desired specifications. It is logical, therefore, that we shouldexpect the 'biodesigner of the future' to be using AI to help write custom DNA sequences that canbe assembled to build whole chromosomes and genomes that drive cells to perform desired tasks.In this project, we plan to see how close we already are to AI-led full sequence design of asynthetic yeast chromosome. In designing, building and testing AI-written regions of yeastchromosomes, we will learn what genomic knowledge and AI design capabilities are currentlymissing that would enable bespoke chromosome design in the next decade. We plan to developsolutions to these current gaps, so that by the end of the project we can use AI to generate the fullsequence of a synthetic chromosome arm, providing the AI with only a list of genes to be included,the peptide sequences of these, their target expression levels and any regulation they require.The project will leverage existing work in our two research groups on building and testingsynthetic chromosome regions in yeast (Ellis), and in designing AI-driven tools for engineeringbiology (Stan). Importantly, it will build on the existing success of key published AI tools that useGANs and CNNs to write synthetic yeast promoters [1], 5'UTRs [2] and 3'UTRs [3] to specification.These 3 genetic parts together account for >85% of non-coding DNA in a yeast chromosome