Department of Genetics, Blavatnik Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA.
Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore.
Nat Commun. 2023 Apr 15;14(1):2162. doi: 10.1038/s41467-023-37876-0.
Generating reference maps of interactome networks illuminates genetic studies by providing a protein-centric approach to finding new components of existing pathways, complexes, and processes. We apply state-of-the-art methods to identify binary protein-protein interactions (PPIs) for Drosophila melanogaster. Four all-by-all yeast two-hybrid (Y2H) screens of > 10,000 Drosophila proteins result in the 'FlyBi' dataset of 8723 PPIs among 2939 proteins. Testing subsets of data from FlyBi and previous PPI studies using an orthogonal assay allows for normalization of data quality; subsequent integration of FlyBi and previous data results in an expanded binary Drosophila reference interaction network, DroRI, comprising 17,232 interactions among 6511 proteins. We use FlyBi data to generate an autophagy network, then validate in vivo using autophagy-related assays. The deformed wings (dwg) gene encodes a protein that is both a regulator and a target of autophagy. Altogether, these resources provide a foundation for building new hypotheses regarding protein networks and function.
生成互作网络参考图谱通过提供一种以蛋白质为中心的方法来发现现有途径、复合物和过程的新组成部分，从而阐明遗传研究。我们应用最先进的方法来鉴定黑腹果蝇的二进制蛋白质-蛋白质相互作用 (PPI)。四次全对酵母双杂交 (Y2H) 筛选了超过 10000 种果蝇蛋白，得到了 2939 种蛋白中 8723 个 PPI 的“FlyBi”数据集。使用正交测定法测试来自 FlyBi 和以前 PPI 研究的数据子集允许对数据质量进行归一化；随后将 FlyBi 和以前的数据整合在一起，得到了扩展的二进制果蝇参考相互作用网络 DroRI，其中包含 6511 种蛋白中的 17232 个相互作用。我们使用 FlyBi 数据生成自噬网络，然后使用与自噬相关的测定法在体内进行验证。畸形翅膀 (dwg) 基因编码一种既是自噬调节剂又是自噬靶标的蛋白质。总之，这些资源为构建关于蛋白质网络和功能的新假设提供了基础。
