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

点击翻译按钮获取中文摘要

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.