PathBIX-a Web Server for Network-based Pathway Annotation with Adaptive Null Models

Overview

Journal Bioinform Adv

Publisher Oxford University Press

Specialty Biology

Date 2023 Jan 26

PMID 36700096

Authors

Miguel Castresana-Aguirre

Emma Persson

Erik L L Sonnhammer

Affiliations

Soon will be listed here.

Abstract

Motivation: Pathway annotation is a vital tool for interpreting and giving meaning to experimental data in life sciences. Numerous tools exist for this task, where the most recent generation of pathway enrichment analysis tools, network-based methods, utilize biological networks to gain a richer source of information as a basis of the analysis than merely the gene content. Network-based methods use the network crosstalk between the query gene set and the genes in known pathways, and compare this to a null model of random expectation.

Results: We developed PathBIX, a novel web application for network-based pathway analysis, based on the recently published ANUBIX algorithm which has been shown to be more accurate than previous network-based methods. The PathBIX website performs pathway annotation for 21 species, and utilizes prefetched and preprocessed network data from FunCoup 5.0 networks and pathway data from three databases: KEGG, Reactome, and WikiPathways.

Availability: https://pathbix.sbc.su.se/.

Contact: erik.sonnhammer@scilifelab.se.

Supplementary Information: Supplementary data are available at online.

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References

Altenhoff A, Garrayo-Ventas J, Cosentino S, Emms D, Glover N, Hernandez-Plaza A . The Quest for Orthologs benchmark service and consensus calls in 2020. Nucleic Acids Res. 2020; 48(W1):W538-W545. PMC: 7319555. DOI: 10.1093/nar/gkaa308. View

Liu Y, Yeh C, Lin K . Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis. Int J Mol Sci. 2019; 20(20). PMC: 6834155. DOI: 10.3390/ijms20204986. View

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

Glaab E, Baudot A, Krasnogor N, Schneider R, Valencia A . EnrichNet: network-based gene set enrichment analysis. Bioinformatics. 2012; 28(18):i451-i457. PMC: 3436816. DOI: 10.1093/bioinformatics/bts389. View

Domingo-Fernandez D, Hoyt C, Bobis-Alvarez C, Marin-Llao J, Hofmann-Apitius M . ComPath: an ecosystem for exploring, analyzing, and curating mappings across pathway databases. NPJ Syst Biol Appl. 2018; 5:3. PMC: 6292919. DOI: 10.1038/s41540-018-0078-8. View

Mubeen S, Hoyt C, Gemund A, Hofmann-Apitius M, Frohlich H, Domingo-Fernandez D . Corrigendum: The Impact of Pathway Database Choice on Statistical Enrichment Analysis and Predictive Modeling. Front Genet. 2020; 11:436. PMC: 7201094. DOI: 10.3389/fgene.2020.00436. View

Persson E, Castresana-Aguirre M, Buzzao D, Guala D, Sonnhammer E . FunCoup 5: Functional Association Networks in All Domains of Life, Supporting Directed Links and Tissue-Specificity. J Mol Biol. 2021; 433(11):166835. DOI: 10.1016/j.jmb.2021.166835. View

Chin S, Wang Y, Thorne N, Teschendorff A, Pinder S, Vias M . Using array-comparative genomic hybridization to define molecular portraits of primary breast cancers. Oncogene. 2006; 26(13):1959-70. DOI: 10.1038/sj.onc.1209985. View

Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M . KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2020; 49(D1):D545-D551. PMC: 7779016. DOI: 10.1093/nar/gkaa970. View

10.

Szklarczyk D, Gable A, Nastou K, Lyon D, Kirsch R, Pyysalo S . The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2020; 49(D1):D605-D612. PMC: 7779004. DOI: 10.1093/nar/gkaa1074. View

11.

Khatri P, Sirota M, Butte A . Ten years of pathway analysis: current approaches and outstanding challenges. PLoS Comput Biol. 2012; 8(2):e1002375. PMC: 3285573. DOI: 10.1371/journal.pcbi.1002375. View

12.

Nguyen T, Shafi A, Nguyen T, Draghici S . Identifying significantly impacted pathways: a comprehensive review and assessment. Genome Biol. 2019; 20(1):203. PMC: 6784345. DOI: 10.1186/s13059-019-1790-4. View

13.

. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res. 2020; 49(D1):D480-D489. PMC: 7778908. DOI: 10.1093/nar/gkaa1100. View

14.

Ogris C, Helleday T, Sonnhammer E . PathwAX: a web server for network crosstalk based pathway annotation. Nucleic Acids Res. 2016; 44(W1):W105-9. PMC: 4987909. DOI: 10.1093/nar/gkw356. View

15.

Carbon S, Ireland A, Mungall C, Shu S, Marshall B, Lewis S . AmiGO: online access to ontology and annotation data. Bioinformatics. 2008; 25(2):288-9. PMC: 2639003. DOI: 10.1093/bioinformatics/btn615. View

16.

Castresana-Aguirre M, Sonnhammer E . Pathway-specific model estimation for improved pathway annotation by network crosstalk. Sci Rep. 2020; 10(1):13585. PMC: 7423893. DOI: 10.1038/s41598-020-70239-z. View

17.

Ogris C, Guala D, Helleday T, Sonnhammer E . A novel method for crosstalk analysis of biological networks: improving accuracy of pathway annotation. Nucleic Acids Res. 2016; 45(2):e8. PMC: 5314790. DOI: 10.1093/nar/gkw849. View

18.

Jaiswal P, Ware D, Ni J, Chang K, Zhao W, Schmidt S . Gramene: development and integration of trait and gene ontologies for rice. Comp Funct Genomics. 2008; 3(2):132-6. PMC: 2447246. DOI: 10.1002/cfg.156. View

19.

Lock A, Harris M, Rutherford K, Hayles J, Wood V . Community curation in PomBase: enabling fission yeast experts to provide detailed, standardized, sharable annotation from research publications. Database (Oxford). 2020; 2020. PMC: 7192550. DOI: 10.1093/database/baaa028. View

20.

Martens M, Ammar A, Riutta A, Waagmeester A, Slenter D, Hanspers K . WikiPathways: connecting communities. Nucleic Acids Res. 2020; 49(D1):D613-D621. PMC: 7779061. DOI: 10.1093/nar/gkaa1024. View