What We Learned From Big Data for Autophagy Research

Abstract

Autophagy is the process by which cytoplasmic components are engulfed in double-membraned vesicles before being delivered to the lysosome to be degraded. Defective autophagy has been linked to a vast array of human pathologies. The molecular mechanism of the autophagic machinery is well-described and has been extensively investigated. However, understanding the global organization of the autophagy system and its integration with other cellular processes remains a challenge. To this end, various bioinformatics and network biology approaches have been developed by researchers in the last few years. Recently, large-scale multi-omics approaches (like genomics, transcriptomics, proteomics, lipidomics, and metabolomics) have been developed and carried out specifically focusing on autophagy, and generating multi-scale data on the related components. In this review, we outline recent applications of in silico investigations and big data analyses of the autophagy process in various biological systems.

Model-based analysis uncovers mutations altering autophagy selectivity in human cancer

“…Known or predicted PPIs and transcriptional regulations between transcription factors and target genes are integrated from 8 public databases, including ARN 32 , BioGrid 37 , IID 38 , inBio MapTM 39 , Mentha 40 , HINT 41 , iRefIndex 42 , and PINA 43 . In total, we obtain 2204 PPIs and 91 transcriptional regulations for the 169 proteins, in which known cancer hallmark proteins are also indicated 35 (Fig. 7 ).…”

“…The central questions include whether the autophagy pathways are targets for recurring molecular alteration in human cancer, and which pathways are targeted 1,2 . To identify the autophagy pathways perturbed in human cancer, we model a LIRCP-regulating network by integrating protein-protein interactions (PPIs) and transcriptional regulations among the 148 identified LIRCPs, 7 LC3 proteins, and 14 proteins regulated by STBD1 since both mechanisms are important for regulating autophagy [32][33][34][35] (Fig. 7).…”

A high mannose concentration is well tolerated by colorectal adenocarcinoma and melanoma cells but toxic to normal human gingival fibroblast: an in vitro investigation

“…Basically, the cell death would be due to autophagy, apoptosis or necrosis. Autophagy is a mechanism in which the cytoplasmic components are engulfed in double-membraned vesicles before the lysosome degrades the vesicles [3]. Apoptosis is defined as the process of cell shrinkage, DNA fragmentation and phagocytosis by macrophages or neighbouring cells [4].…”

Autophagy/virophagy: a “disposal strategy” to combat COVID-19

“…Additionally, as a multi-step and well-orchestrated (i.e., regulated by over 40 autophagy-related [ATG] proteins and numerous auxiliary/accessory proteins) process for maintaining homeostasis in the complex landscape of the eukaryotic cell, autophagy is the only pathway that is capable of degrading entire cellular organelles (e.g., mitochondria, peroxisomes, endoplasmic reticulum, the nucleus) and invading pathogens, including fungi, parasites, bacteria and viruses either randomly or in a targeted/selected fashion. Selective autophagy captures its cargo via the recruitment of selective autophagy receptors, including those involved in the autophagic degradation of viruses and viral-derived antigens via a specialized form of selective autophagy known as xenophagy (also termed virophagy, when referring to viruses) [7][8][9][10][11].…”

“…The existing and newly-generated scientific evidence and publications allow for speculation that autophagy/virophagy induction might counteract CoV infection at different levels, although more specific data are certainly required. Irrespective of whether autophagy/virophagy modulation will eventually be part of the "disposal strategies" in the fight against COVID-19, it is essential to further establish and secure global healthcare as well as to promote and extend robust research including the potential role of autophagy/virophagy as it pertains to infectious diseases, including CoVs [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. The biomedical research enterprise, scientists and researchers, including auto-phagy researchers, are more than willing to respond to the challenge of COVID-19; however, it has become apparent that much needed coordination among important constituencies is lacking.…”