The Criminal Science and Technology Department, Zhejiang Police College, 555 Binwen Road, Binjiang District, Hangzhou, Zhejiang Province, People's Republic of China.
The department of gastroenterology, The First Affiliated Hospital of Xi'an Jiao Tong University, 277 Yanta West Road, Yanta District, Xi'an, Shanxi Province, People's Republic of China.
Sci Rep. 2017 Mar 15;7:44391. doi: 10.1038/srep44391.
Autophagy is a protective and life-sustaining process in which cytoplasmic components are packaged into double-membrane vesicles and targeted to lysosomes for degradation. Accumulating evidence supports that autophagy is associated with several pathological conditions. However, research on the functional cross-links between autophagy and disease genes remains in its early stages. In this study, we constructed a disease-autophagy network (DAN) by integrating known disease genes, known autophagy genes and protein-protein interactions (PPI). Dissecting the topological properties of the DAN suggested that nodes that both autophagy and disease genes (inter-genes), are topologically important in the DAN structure. Next, a core network from the DAN was extracted to analyze the functional links between disease and autophagy genes. The genes in the core network were significantly enriched in multiple disease-related pathways, suggesting that autophagy genes may function in various disease processes. Of 17 disease classes, 11 significantly overlapped with autophagy genes, including cancer diseases, metabolic diseases and hematological diseases, a finding that is supported by the literatures. We also found that autophagy genes have a bridging role in the connections between pairs of disease classes. Altogether, our study provides a better understanding of the molecular mechanisms underlying human diseases and the autophagy process.
自噬是一种保护和维持生命的过程，其中细胞质成分被包裹在双层膜泡中，并靶向溶酶体进行降解。越来越多的证据表明，自噬与多种病理状况有关。然而，关于自噬与疾病基因之间功能联系的研究仍处于早期阶段。在这项研究中，我们通过整合已知的疾病基因、已知的自噬基因和蛋白质-蛋白质相互作用（PPI）构建了一个疾病-自噬网络（DAN）。对 DAN 的拓扑性质进行剖析表明，自噬和疾病基因（互基因）都在 DAN 结构中具有拓扑重要性的节点。接下来，从 DAN 中提取了一个核心网络来分析疾病和自噬基因之间的功能联系。核心网络中的基因在多个与疾病相关的途径中显著富集，这表明自噬基因可能在多种疾病过程中发挥作用。在 17 种疾病类别中，有 11 种与自噬基因显著重叠，包括癌症疾病、代谢疾病和血液疾病，这一发现得到了文献的支持。我们还发现，自噬基因在疾病类别对之间的连接中具有桥梁作用。总之，我们的研究为理解人类疾病和自噬过程的分子机制提供了更好的认识。
