AutophagyNet: high-resolution data source for the analysis of autophagy and its regulation

ABSTRACT

Macroautophagy/autophagy is a highly-conserved catabolic procss eliminating dysfunctional cellular components and invading pathogens. Autophagy malfunction contributes to disorders such as cancer, neurodegenerative and inflammatory diseases. Understanding autophagy regulation in health and disease has been the focus of the last decades. We previously provided an integrated database for autophagy research, the Autophagy Regulatory Network (ARN). For the last eight years, this resource has been used by thousands of users. Here, we present a new and upgraded resource, AutophagyNet. It builds on the previous database but contains major improvements to address user feedback and novel needs due to the advancement in omics data availability. AutophagyNet contains updated interaction curation and integration of over 280,000 experimentally verified interactions between core autophagy proteins and their protein, transcriptional and post-transcriptional regulators as well as their potential upstream pathway connections. AutophagyNet provides annotations for each core protein about their role: 1) in different types of autophagy (mitophagy, xenophagy, etc.); 2) in distinct stages of autophagy (initiation, expansion, termination, etc.); 3) with subcellular and tissue-specific localization. These annotations can be used to filter the dataset, providing customizable download options tailored to the user’s needs. The resource is available in various file formats (e.g. CSV, BioPAX and PSI-MI), and data can be analyzed and visualized directly in Cytoscape. The multi-layered regulation of autophagy can be analyzed by combining AutophagyNet with tissue- or cell type-specific (multi-)omics datasets (e.g. transcriptomic or proteomic data). The resource is publicly accessible at http://autophagynet.org.

Abbreviations: ARN: Autophagy Regulatory Network; ATG: autophagy related; BCR: B cell receptor pathway; BECN1: beclin 1; GABARAP: GABA type A receptor-associated protein; IIP: innate immune pathway; LIR: LC3-interacting region; lncRNA: long non-coding RNA; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; miRNA: microRNA; NHR: nuclear hormone receptor; PTM: post-translational modification; RTK: receptor tyrosine kinase; TCR: T cell receptor; TLR: toll like receptor.

KEYWORDS:

• Autophagy regulation
• big data
• multi-omics
• network resource
• signaling

Acknowledgements

We thank the comments and feedback of the users of Autophagy Regulatory Network and the pilot of the AutophagyNet web resources as well as the suggestions and ideas from the past and current members of the LINKgroup, Vellai Lab, and Korcsmaros Lab (previously NetBiol group).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data can be freely downloaded from http://autophagynet.org. The workflow for building the database can be accessed on GitHub: https://github.com/korcsmarosgroup/AutophagyNetDB

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15548627.2023.2247737

Additional information

Funding

The work was supported by the Bundesministerium für Bildung und Forschung [031L0181B]; National Research, Development and Innovation Office [NKFIH FK-134267]; BBSRC National Capability in e-Infrastructure [BBS/E/T/000PR9814]; Division of Digestive Diseases at Imperial College London UK Research and Innovation (UKRI) Biotechnological and Biosciences Research Council (BBSRC) Core Strategic Programme Grant for Genomes to Food Security [BB/CSP1720/1, BBS/E/T/000PR9819, BBS/E/T/000PR9817]; BBSRC ISP grant for Gut Microbes and Health (BB/R012490/1) [BBS/E/F/000PR10353, BBS/E/F/000PR10355]; UKRI BBSRC Core Capability Grant [BB/CCG1720/1]; ELKH/MTA-ELTE Genetics Research Group [01062]; Hungarian National Research, Development and Innovation Office [K131458, PD131839, K132439]; BBSRC Norwich Research Park Biosciences Doctoral Training Partnership [BB/M011216/1, BB/S50743X/1].