Improving accuracy, coverage, and sustainability of functional protein annotation in InterPro, Pfam and FunFam using Deep Learning methods

蛋白质是负责细胞内生物过程的大分子。在它们最基本的水平上，它们由氨基酸序列组成，由基因中的核苷酸序列(生命的ATGC构件)决定。蛋白质通常折叠成三维结构，使它们能够与其他分子相互作用并发挥其功能。测序技术的最新进展导致蛋白质数据的大量积累，我们产生新蛋白质序列的能力已经超过了我们充分了解它们功能的能力。因此，开发计算方法来识别特征蛋白质和未特征蛋白质之间的序列或结构相似性以将功能信息从前者传递到后者是至关重要的。InterPro、Pfam和FunFam是世界领先的英国资源，它们将相似的蛋白质序列组合在一起，形成蛋白质家族。Pfam是包含功能注释的蛋白质结构域家族的集合。FunFam专注于共享共同功能的蛋白质结构域。InterPro将包括Pfam和FunFam在内的13个专家蛋白质数据库中的信息合并为一个可搜索的资源，并进一步注释蛋白质家族。在过去的几年中，人工智能方法已成功地应用于几个生物学应用。例如，DeepMind的AlphaFold彻底改变了蛋白质序列如何折叠成三维结构的预测。我们的合作者正在开发几个有希望的工具，以使用深度学习(DL)更好地识别蛋白质家族。这些方法在准确性、覆盖率和计算效率方面都优于目前最先进的方法，从而使它们更具环境可持续性。在这个雄心勃勃的项目中，我们将提高InterPro、Pfam和FunFam的效率、准确性和可持续性。这将通过减少近30年前建立的Pfam的技术债务，采用DL方法来加强蛋白质序列到家族的分类，以及显著减少序列注释的碳足迹来实现。最后，我们将改进农业上重要的植物病原体的注释，从而创建数百个额外的InterPro和Pfam条目。

Proteins are macromolecules responsible for biological processes in the cell. At their most basic level, they consist of a sequence of amino acids, determined by the sequence of nucleotides (the ATGC building blocks of life) in a gene. Proteins usually fold into three-dimensional structures, allowing them to interact with other molecules and perform their functions. Recent advances in sequencing technologies have led to a substantial accumulation of protein data, and our capacity of generating new protein sequences has surpassed our ability to fully understand their functions. Therefore, it is crucial to develop computational methods that identify sequence or structural similarities between characterised and uncharacterised proteins to transfer functional information from the former to the latter.InterPro, Pfam and FunFam are world-leading, UK-based resources that group similar protein sequences together, forming protein families. Pfam is a collection of protein domain families containing functional annotations. FunFam focuses on protein structural domains that share a common function. InterPro merges information from 13 expert protein databases, including Pfam and FunFam, into a single searchable resource, and further annotates protein families.In the past few years, Artificial Intelligence methods have been successfully applied to several biological applications. For instance, DeepMind's AlphaFold has revolutionised the prediction of how protein sequences fold into three-dimensional structures. Several promising tools are being developed by our collaborators to better identify protein families using Deep Learning (DL). These methods outperform current state-of-the-art approaches in terms of accuracy, coverage and computing efficiency, thus making them more environmentally sustainable.In this ambitious project, we will improve the efficiency, accuracy, and sustainability of InterPro, Pfam and FunFam. This will be accomplished by reducing the technical debt of Pfam, established almost three decades ago, adopting DL approaches to enhance the classification of protein sequences into families, and significantly reducing the carbon footprint of sequence annotation. Finally, we will improve the annotation of agriculturally important plant pathogens, resulting in the creation of hundreds of additional InterPro and Pfam entries.