GO annotation: maximizing the potential of Drosophila research to benefit human health

小小的、无害的果蝇--黑腹果蝇--是如何彻底改变了对遗传、发育、生长、衰老和疾病的理解，从而造福于人类的健康和福祉的？答案是：我们并没有那么不同。果蝇与我们有许多共同点-身体部位：四肢，大脑，心脏，眼睛，肾脏;它的行为方式相似：睡觉，行走，记忆，忘记;并以类似的方式感知世界：视觉，嗅觉，味觉和触觉。在DNA水平上，我们可以看到果蝇和人类的许多基因是等同的，许多基本的生理、细胞生物学和行为机制从根本上是相同的。我们可以在苍蝇身上做许多研究，而这些研究在更复杂的生物体中是不可能的--特别是在人类身上，无论是出于实践还是道德上的原因。重要的是，人类疾病可以在苍蝇中“建模”-例如通过在等效的苍蝇基因中进行相同的突变或将苍蝇暴露于有害的环境中。通过这种方式，我们“给”果蝇人类疾病-从阿尔茨海默氏症到肾结石。然后我们可以利用这些苍蝇来发现导致疾病症状的原因，并帮助开发治疗方法。这看起来很了不起，但果蝇可以为患有复杂疾病的个人和家庭提供真实的答案。 所有使用果蝇的研究产生了大量的信息-超过任何研究人员可以阅读（超过2,800篇研究文章/年）。这就是生物数据库的用武之地：它们有专门的人员（策展人）团队，他们阅读已发表的研究论文，并以标准化的方式将信息输入计算机数据库。这意味着信息可以很容易地找到，快速吸收，与其他数据进行比较，并整合以产生新的发现。 我们项目的目的是使用一个标准化的科学词汇表，称为基因本体论（GO），来描述基因做什么和它们在哪里做。拥有一个标准化的词汇表的重要性在于它统一了用于基础和医学研究的不同生物体的研究结果，包括苍蝇，老鼠，斑马鱼和酵母。这些标准化的描述使人们能够快速了解许多基因的功能，并在生物体之间进行比较。尽管进行了深入的研究，但我们仍然不知道大量基因的功能-大约22%的果蝇基因和20%的人类基因缺乏已知的功能。.发现果蝇基因的功能并用GO记录下来，可以让我们推断出同等的人类基因可能具有类似的功能，帮助研究人员计划实验来了解人类基因。因此，继续用GO描述基因功能是研究进展的重要活动。除了注释新表征的果蝇基因外，我们还将对新发现的关键领域和选定的医学领域进行集中的GO策展。其中包括：神经系统疾病如帕金森氏症和运动神经元疾病中被破坏的过程;驱动侵袭性肿瘤的过程;以及病毒感染，关于病毒感染的病理学和蚊子等昆虫的病毒传播。这种集中的管理将在咨询该领域专家的情况下进行，并将改善GO的词汇以及注释的一致性和准确性。总之，该项目旨在促进从果蝇研究中获得的知识向医学界的转移，最终帮助开发人类疾病的有效治疗方法。

How can it be that the tiny, innocuous fruit fly, Drosophila melanogaster, has revolutionised the understanding of genetics, development, growth, aging and disease for the benefit of human health and well-being? The answer is: we are not that different. The fruit fly has many commonalities with us - body parts: limbs, brain, heart, eyes, kidney; it behaves in similar ways: sleeps, walks, remembers, forgets; and perceives the world in the similar manner: sight, smell, taste and touch. At the level of DNA we can see that many genes in Drosophila and humans are equivalent and many basic physiological, cell biological and behavioural mechanisms are fundamentally the same. We can do many studies in flies that simply would not be possible in more complex organisms - especially in humans, both for practical and ethical reasons. Importantly, human diseases can be 'modelled' in flies - for example by making the same mutations in the equivalent fly genes or by exposing flies to damaging environments. In this way we 'give' Drosophila human diseases - from Alzheimer's disease to kidney stones. Then we can use these flies to discover what causes the disease symptoms and help develop treatments. It seems remarkable, but fruit flies can provide real answers to individuals and families with complex diseases. All the research using Drosophila generates a tremendous amount of information - more than any researcher can read (over 2,800 research articles/year). This is where biological databases come in: they have dedicated teams of people (curators) who read the published research papers and enter the information into a computer database in a standardized manner. This means that the information can be easily found, rapidly assimilated, compared with other data, and integrated to generate new discoveries. The aim of our project is to use a standardized scientific vocabulary, called the Gene Ontology (GO), to describe what genes do and where they do it. The importance of having a standardized vocabulary is that it unifies research findings across different organisms that are used for basic and medical research, including flies, mice, zebrafish and yeast. These standardized descriptions make it possible to rapidly understand the function of many genes and compare across organisms. Despite intensive research, we still do not know what a surprisingly large number of genes do - approximately 22% of Drosophila genes and 20% of human genes lack a known function. . Discovering what a Drosophila gene does and recording this with the GO allows us to infer that the equivalent human gene is likely to have a similar function, helping researchers plan experiments to understand the human gene. Thus, continued description of gene function with the GO is a vital activity for research progress. In addition to annotating newly characterized Drosophila genes, we will undertake focused GO curation on key areas of new discovery and selected areas of medical interest. These include: processes that are disrupted in neurological diseases, such as Parkinson's and motor neurone disease; processes that drive aggressive tumours; and viral infection, with regard to both the pathology of viral infection and viral spread by insects such as mosquitoes. Such focused curation will be conducted with consultation of experts in the field, and will improve the vocabulary of the GO as well as the consistency and accuracy of the annotations. In summary, this project aims to facilitate the transfer of knowledge gained from research on fruit flies to the medical community, ultimately helping the development of effective treatments of human diseases.