. 2021 Jan 7;22(2):532. doi: 10.3390/ijms22020532

Table 1.

Proteomics SARS-CoV-2 studies in cellular systems: network and enrichment analysis.

References	Biological Systems	Interactors Identification Methods	PPI Analysis	SARS-CoV-2-Human Interaction Network and Enrichment Analysis (Main Pathways)	Data Availability and Web Resources
Gordon et al. [17]	Transient transfection in HEK-293 cells for PPI studies; Vero E6 cells for drug repurposing.	AP-MS: either N- or C- terminus 2xStrep tagging followed by AP-MS.	SAINTexpress ⁽¹⁾; MiST ⁽²⁾; Cytoscape; GO ⁽³⁾ enrichment analysis.	DNA replication, epigenetic and gene-expression regulators, vesicle trafficking, lipid modification, RNA processing and regulation, ubiquitin ligases, signaling, nuclear transport machinery, cytoskeleton, mitochondria and the extracellular matrix.	MS raw data deposited to the PX ⁽⁴⁾ Consortium (www.ebi.ac.uk/pride/archive/projects/PXD018117). PPI networks uploaded to NDEx ⁽⁵⁾ (https://public.ndexbio.org/#/network/43803262-6d69-11ea-bfdc-0ac135e8bacf).
Gordon et al. [18]	Transient transfection in HEK-293 cells for PPI studies; HeLa cells for IF⁵ experiments; A549-ACE2 and Caco2 cells for validation on viral life cycle; Vero E6 and A549-ACE2 cells for drug repurposing.	AP-MS: either N- or C- terminus 2xStrep tagging followed by AP-MS.	SAINTexpress; MiST; Cytoscape; GO ⁽³⁾ enrichment analysis.	Regulation of RNA metabolism and ribosome biogenesis, endosomal and Golgi vesicle transport, proteasomal catabolism, cellular response to heat and regulation of intracellular protein transport.	MS-proteomics data deposited to the PX ⁽⁶⁾ Consortium (https://www.ebi.ac.uk/pride/archive/projects/PXD021588). PPI networks can be found either in NDEx ⁽⁵⁾ and at https://kroganlab.ucsf.edu/network-maps.
Davies et al. [19]	Transient transfection in HEK-293 cells.	AP-MS: either N- (nsp2) or C- (nsp4) terminus FLAG tagging followed by AP-MS.	R statistics software. Cytoscape; GO ⁽³⁾ enrichment analysis.	Nsp2 interactors are involved in a number of host cell processes, including metabolic processing and transport. Nsp4 interactors showed multiple enriched biological processes, such as cell organization and biogenesis, transport, and metabolic processes.	N/A
Li et al. [20]	Transient transfection in HEK-293 cells. PBMC for proteomic perturbation in COVID-19 patients primary cells.	AP-MS: N- terminus 3xFlag-tagging followed by AP-MS.	MiST; Cytoscape; GO ⁽³⁾ enrichment analysis.	Inflammation and immune responses, ATP biosynthesis and metabolic processes, nucleotide-excision repair, protein methylation and alkylation, translation initiation, reactive oxygen species metabolic process, ER stress, and mRNA transport.	Datasets deposited to the PX ⁽⁴⁾ Consortium (http://proteomecentral.proteomexchange.org) via the iProX partner repository (dataset identifier IPX0002285000).
Stukalov et al. [21]	Lentiviral mediated transduction of A549 cells for PPI identification. A549-ACE2 for both OMICS perturbation and drug repurposing.	AP-MS: C- terminus HA tagging followed by AP-MS.	R statistics software; GO ⁽³⁾ enrichment analysis.	Stress and DNA damage response, regulation of transcription, cell junction organization, cell survival, motility and innate immune responses.	N/A
Samavarchi-Tehrani et al. [22]	A549 cells transduced by lentiviral constructs (except for nsp1 and nsp3, whose constructs where transfected).	BioID: miniTurbo enzyme fused separately at both N- and C- terminus of each bait, modified proteins purification followed by MS.	SAINTexpress; Cytoscape; GO ⁽³⁾ enrichment analysis; Humancellmap.org.	Regulation of cell cycle processes, antigen processing, viral genome replication, transcription, regulation of innate immunity, DNA damage checkpoint, histone binding, proteasomal degradation.	Virus–host proximity interactome dataset is available at https://covid19interactome.org/
St-Germain et al. [23]	Stably transfected HEK-293 cells	BioID: BirA* enzyme fused at the N- terminus of 14 viral baits, modified proteins purification followed by MS.	SAINTexpress; Cytoscape; GO ⁽³⁾ enrichment analysis.	Vesicle-mediated transport, Golgi vesicle transport, ER to Golgi vesicle-mediated transport, response to ER stress, retrograde transport endosome to Golgi, lipid biosynthetic process, ER organization, retrograde vesicle-mediated transport, COPII-coated vesicle budding.	All virus MS data available at https://massive.ucsd.edu
Laurent et al. [24]	Stably transfected HEK-293 cells	BioID: BirA* enzyme fused separately at both N- and C- terminus of each bait, modified proteins purification followed by MS.	ToppCluster; Metascape; GO ⁽³⁾ enrichment analysis.	Innate immune response, autophagy, apoptosis, lipid metabolism, vesicular transport, chromatin remodeling, mRNA processing, inflammation, viral signal transduction, nucleic acid processing, cell adhesion and migration, platelet activation, coagulation regulation, olfactory receptors homeostasis and olfactory cell signal transmission.	Data exploitation available at http://www.sars-cov-2-interactome.org/

⁽¹⁾ SAINT: Significance Analysis of INTeractome. ⁽²⁾ MiST: Mass spectrometry interaction STatistics. ⁽³⁾ GO: Gene Ontology. ⁽⁴⁾ PX: ProteomeXchange. ⁽⁵⁾ IF immunofluorescence ⁽⁶⁾ NDEx: Network Data Exchange.