Using Reactome to build an autophagy mechanism knowledgebase

ABSTRACT The 21st century has revealed much about the fundamental cellular process of autophagy. Autophagy controls the catabolism and recycling of various cellular components both as a constitutive process and as a response to stress and foreign material invasion. There is considerable knowledge of the molecular mechanisms of autophagy, and this is still growing as new modalities emerge. There is a need to investigate autophagy mechanisms reliably, comprehensively and conveniently. Reactome is a freely available knowledgebase that consists of manually curated molecular events (reactions) organized into cellular pathways (https://reactome.org/). Pathways/reactions in Reactome are hierarchically structured, graphically presented and extensively annotated. Data analysis tools, such as pathway enrichment, expression data overlay and species comparison, are also available. For customized analysis, information can also be programmatically queried. Here, we discuss the curation and annotation of the molecular mechanisms of autophagy in Reactome. We also demonstrate the value that Reactome adds to research by reanalyzing a previously published work on genome-wide CRISPR screening of autophagy components. Abbreviations: CMA: chaperone-mediated autophagy; GO: Gene Ontology; MA: macroautophagy; MI: microautophagy; MTOR: mechanistic target of rapamycin kinase; SQSTM1: sequestosome 1

[1]  Thawfeek M. Varusai,et al.  The reactome pathway knowledgebase , 2019, Nucleic Acids Res..

[2]  Benjamin M. Good,et al.  Gene Ontology Causal Activity Modeling (GO-CAM) moves beyond GO annotations to structured descriptions of biological functions and systems , 2019, Nature Genetics.

[3]  Ugur Dogrusoz,et al.  Systems Biology Graphical Notation: Process Description language Level 1 Version 2.0 , 2019, J. Integr. Bioinform..

[4]  Henning Hermjakob,et al.  Reactome and ORCID—fine-grained credit attribution for community curation , 2019, Database J. Biol. Databases Curation.

[5]  The UniProt Consortium,et al.  UniProt: a worldwide hub of protein knowledge , 2018, Nucleic Acids Res..

[6]  The Gene Ontology Consortium,et al.  The Gene Ontology Resource: 20 years and still GOing strong , 2018, Nucleic Acids Res..

[7]  Henning Hermjakob,et al.  Complex Portal 2018: extended content and enhanced visualization tools for macromolecular complexes , 2018, Nucleic Acids Res..

[8]  I. Dikic,et al.  Mechanism and medical implications of mammalian autophagy , 2018, Nature reviews. Molecular cell biology.

[9]  Astrid Gall,et al.  Ensembl 2018 , 2017, Nucleic Acids Res..

[10]  Ruth C Lovering,et al.  Exploring autophagy with Gene Ontology , 2016, Autophagy.

[11]  T. Noda.  Autophagy in the context of the cellular membrane-trafficking system: the enigma of Atg9 vesicles , 2017, Biochemical Society transactions.

[12]  E. Baehrecke,et al.  Cleaning House: Selective Autophagy of Organelles. , 2017, Developmental cell.

[13]  John A. Tallarico,et al.  Functional CRISPR screening identifies the ufmylation pathway as a regulator of SQSTM1/p62 , 2016, eLife.

[14]  Christoph Steinbeck,et al.  ChEBI in 2016: Improved services and an expanding collection of metabolites , 2015, Nucleic Acids Res..

[15]  E. Baehrecke,et al.  Current questions and possible controversies in autophagy , 2015, Cell Death Discovery.

[16]  Guanming Wu,et al.  ReactomeFIViz : a Cytoscape app for pathway and network-based data analysis , 2022 .

[17]  Guanming Wu,et al.  A controlled vocabulary for pathway entities and events , 2014, Database J. Biol. Databases Curation.

[18]  Rafael C. Jimenez,et al.  The IntAct molecular interaction database in 2012 , 2011, Nucleic Acids Res..

[19]  Hideaki Sugawara,et al.  The Autophagy Database: an all-inclusive information resource on autophagy that provides nourishment for research , 2010, Nucleic Acids Res..

[20]  A. Cuervo,et al.  Autophagic pathways and metabolic stress , 2010, Diabetes, obesity & metabolism.

[21]  D. Klionsky,et al.  Regulation mechanisms and signaling pathways of autophagy. , 2009, Annual review of genetics.

[22]  Guido Kroemer,et al.  Autophagy in the Pathogenesis of Disease , 2008, Cell.

[23]  De,et al.  Tissue Fractionation Studies , 2005 .

[24]  Ana Maria Cuervo,et al.  Autophagy: Many paths to the same end , 2004, Molecular and Cellular Biochemistry.

[25]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[26]  Y. Ohsumi,et al.  Isolation and characterization of autophagy‐defective mutants of Saccharomyces cerevisiae , 1993, FEBS letters.

[27]  R. Wattiaux,et al.  Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. , 1955, The Biochemical journal.