ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways.
Algorithms
Bronchi
/ virology
COVID-19
/ metabolism
Cluster Analysis
Computational Biology
/ methods
Gene Expression Profiling
Gene Expression Regulation, Viral
Host-Pathogen Interactions
Humans
Interdisciplinary Research
Lung
/ virology
Models, Statistical
SARS-CoV-2
/ pathogenicity
Signal Transduction
Systems Biology
Transcriptome
Workflow
Journal
PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
26
06
2020
accepted:
10
01
2021
revised:
16
02
2021
pubmed:
4
2
2021
medline:
2
3
2021
entrez:
3
2
2021
Statut:
epublish
Résumé
The SARS-CoV-2 pandemic of 2020 has mobilised scientists around the globe to research all aspects of the coronavirus virus and its infection. For fruitful and rapid investigation of viral pathomechanisms, a collaborative and interdisciplinary approach is required. Therefore, we have developed ViralLink: a systems biology workflow which reconstructs and analyses networks representing the effect of viruses on intracellular signalling. These networks trace the flow of signal from intracellular viral proteins through their human binding proteins and downstream signalling pathways, ending with transcription factors regulating genes differentially expressed upon viral exposure. In this way, the workflow provides a mechanistic insight from previously identified knowledge of virally infected cells. By default, the workflow is set up to analyse the intracellular effects of SARS-CoV-2, requiring only transcriptomics counts data as input from the user: thus, encouraging and enabling rapid multidisciplinary research. However, the wide-ranging applicability and modularity of the workflow facilitates customisation of viral context, a priori interactions and analysis methods. Through a case study of SARS-CoV-2 infected bronchial/tracheal epithelial cells, we evidence the functionality of the workflow and its ability to identify key pathways and proteins in the cellular response to infection. The application of ViralLink to different viral infections in a context specific manner using different available transcriptomics datasets will uncover key mechanisms in viral pathogenesis.
Identifiants
pubmed: 33534793
doi: 10.1371/journal.pcbi.1008685
pii: PCOMPBIOL-D-20-01119
pmc: PMC7886129
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008685Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/F/000PR10353
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/F/000PR10355
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/T/000PR9817
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Nat Microbiol. 2020 Nov;5(11):1330-1339
pubmed: 32704094
Nat Genet. 2015 Feb;47(2):106-14
pubmed: 25501392
Integr Biol (Camb). 2017 Feb 20;9(2):97-108
pubmed: 28106223
Genome Res. 2019 Aug;29(8):1363-1375
pubmed: 31340985
Mol Syst Biol. 2021 Apr;17(4):e10232
pubmed: 33904651
Immunology. 2020 Jul;160(3):261-268
pubmed: 32460357
J Clin Med. 2020 Apr 01;9(4):
pubmed: 32244779
Lancet Respir Med. 2020 Jun;8(6):547-548
pubmed: 32401711
Mol Syst Biol. 2021 Jan;17(1):e9730
pubmed: 33502086
Cell Rep. 2020 Jul 7;32(1):107863
pubmed: 32610043
PLoS Pathog. 2020 Jul 29;16(7):e1008737
pubmed: 32726355
Sci Rep. 2020 Aug 12;10(1):13585
pubmed: 32788619
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
FEMS Immunol Med Microbiol. 2006 Mar;46(2):236-43
pubmed: 16487305
Nat Med. 2020 Jun;26(6):842-844
pubmed: 32398875
Nat Rev Genet. 2011 Jan;12(1):56-68
pubmed: 21164525
Nat Protoc. 2008;3(10):1616-29
pubmed: 18802442
Nat Genet. 2016 Aug;48(8):838-47
pubmed: 27322546
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nucleic Acids Res. 2014 Jan;42(Database issue):D358-63
pubmed: 24234451
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D452-5
pubmed: 14681455
Emerg Microbes Infect. 2020 Dec;9(1):558-570
pubmed: 32172672
Cell Death Dis. 2021 Aug 12;12(8):788
pubmed: 34385425
bioRxiv. 2021 Dec 09;:
pubmed: 33083801
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Curr Protoc Bioinformatics. 2014 Sep 08;47:8.13.1-24
pubmed: 25199793
Bioinformatics. 2013 Nov 1;29(21):2757-64
pubmed: 23986566
J Transl Med. 2020 Jun 10;18(1):233
pubmed: 32522207
Scientometrics. 2021;126(1):831-842
pubmed: 32904414
Nucleic Acids Res. 2011 Jan;39(Database issue):D691-7
pubmed: 21067998
BioData Min. 2008 Nov 28;1:12
pubmed: 19040716
Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515
pubmed: 30395287
Med. 2021 Jan 15;2(1):99-112.e7
pubmed: 32838362
F1000Res. 2019 Oct 18;8:1774
pubmed: 31819800
Cytokine. 2008 Sep;43(3):350-8
pubmed: 18703349
Nucleic Acids Res. 2013 Jan;41(Database issue):D991-5
pubmed: 23193258
Cell. 2020 May 14;181(4):954-954.e1
pubmed: 32413300
Cell Discov. 2020 Mar 16;6:14
pubmed: 32194980
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Genome Res. 2013 Feb;23(2):365-76
pubmed: 23064748
Nucleic Acids Res. 2016 Jan 4;44(D1):D457-62
pubmed: 26476454
Nat Rev Immunol. 2020 May;20(5):269-270
pubmed: 32273594
Virus Res. 2018 Jul 15;253:48-61
pubmed: 29864503
Cells. 2020 May 21;9(5):
pubmed: 32455748
Nat Commun. 2018 Jan 2;9(1):20
pubmed: 29295995
Nat Rev Genet. 2017 Sep;18(9):551-562
pubmed: 28607512
Nat Biotechnol. 2020 Aug;38(8):970-979
pubmed: 32591762
Nucleic Acids Res. 2018 Jan 4;46(D1):D649-D655
pubmed: 29145629
Front Genet. 2015 Aug 04;6:260
pubmed: 26300911
Cold Spring Harb Perspect Biol. 2012 Sep 01;4(9):a006114
pubmed: 22952390
BMC Bioinformatics. 2003 Jan 13;4:2
pubmed: 12525261
Trends Endocrinol Metab. 1998 Jan-Feb;9(1):27-31
pubmed: 18406231
Cell. 2020 May 28;181(5):1036-1045.e9
pubmed: 32416070
Nucleic Acids Res. 2017 Jan 4;45(D1):D331-D338
pubmed: 27899567
Gene Regul Syst Bio. 2008 May 15;2:193-201
pubmed: 19787083
Curr Opin Syst Biol. 2017 Feb;1:16-24
pubmed: 29104946
Antiviral Res. 2020 Jun;178:104791
pubmed: 32275914
Science. 2020 Jul 3;369(6499):50-54
pubmed: 32358202
Mol Biosyst. 2016 Feb;12(2):477-9
pubmed: 26661513
Clin Infect Dis. 2021 Aug 2;73(3):376-385
pubmed: 32463434
NPJ Syst Biol Appl. 2019 Nov 11;5:40
pubmed: 31728204
Front Genet. 2019 Nov 22;10:1203
pubmed: 31824580
PLoS Comput Biol. 2017 Oct 12;13(10):e1005579
pubmed: 29023448
Nature. 2020 Jul;583(7816):459-468
pubmed: 32353859
Nat Methods. 2016 Nov 29;13(12):966-967
pubmed: 27898060
Biochem J. 2014 Dec 15;464(3):439-47
pubmed: 25271362
Proc Natl Acad Sci U S A. 2021 May 11;118(19):
pubmed: 33906951