{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T01:53:21Z","timestamp":1774490001929,"version":"3.50.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["207769\/A\/17\/Z"],"award-info":[{"award-number":["207769\/A\/17\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gene and protein interaction experiments provide unique opportunities to study the molecular wiring of a cell. Integrating high-throughput functional genomics data with this information can help identifying networks associated with complex diseases and phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Here we introduce an integrated statistical framework to test network properties of single and multiple genesets under different interaction models. We implemented this framework as an open-source software, called Python Geneset Network Analysis (PyGNA). Our software is designed for easy integration into existing analysis pipelines and to generate high quality figures and reports. We also developed PyGNA to take advantage of multi-core systems to generate calibrated null distributions on large datasets. We then present the results of extensive benchmarking of the tests implemented in PyGNA and a use case inspired by RNA sequencing data analysis, showing how PyGNA can be easily integrated to study biological networks. PyGNA is available at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/github.com\/stracquadaniolab\/pygna\">http:\/\/github.com\/stracquadaniolab\/pygna<\/jats:ext-link>\n                      and can be easily installed using the PyPi or Anaconda package managers, and Docker.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We present a tool for network-aware geneset analysis. PyGNA can either be readily used and easily integrated into existing high-performance data analysis pipelines or as a Python package to implement new tests and analyses. With the increasing availability of population-scale omic data, PyGNA provides a viable approach for large scale geneset network analysis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12859-020-03801-1","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T06:02:47Z","timestamp":1603346567000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PyGNA: a unified framework for geneset network analysis"],"prefix":"10.1186","volume":"21","author":[{"given":"Viola","family":"Fanfani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Cassano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9819-3645","authenticated-orcid":false,"given":"Giovanni","family":"Stracquadanio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"3801_CR1","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41576-019-0093-7","volume":"20","author":"T Stuart","year":"2019","unstructured":"Stuart T, Satija R. Integrative single-cell analysis. Nat Rev Genet. 2019;20:257.","journal-title":"Nat Rev Genet"},{"key":"3801_CR2","unstructured":"Luck K, Kim DK, Lambourne L, Spirohn K, Begg BE, Bian W, Brignall R, Cafarelli T, Campos-Laborie FJ, Charloteaux B, et al.: A reference map of the human protein interactome. bioRxiv, 605451 (2019)"},{"issue":"suppl\u20131","key":"3801_CR3","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1093\/nar\/gkj109","volume":"34","author":"C Stark","year":"2006","unstructured":"Stark C, Breitkreutz B-J, Reguly T, Boucher L, Breitkreutz A, Tyers M. Biogrid: a general repository for interaction datasets. Nucleic Acids Res. 2006;34(suppl\u20131):535\u20139.","journal-title":"Nucleic Acids Res"},{"key":"3801_CR4","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1093\/bioinformatics\/bts389","volume":"28","author":"E Glaab","year":"2012","unstructured":"Glaab E, Baudot A, Krasnogor N, Schneider R, Valencia A. EnrichNet: network-based gene set enrichment analysis. Bioinformatics. 2012;28:451\u20137.","journal-title":"Bioinformatics"},{"issue":"D1","key":"3801_CR5","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1093\/nar\/gky1038","volume":"47","author":"H Mi","year":"2018","unstructured":"Mi H, Muruganujan A, Ebert D, Huang X, Thomas PD. PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res. 2018;47(D1):419\u201326.","journal-title":"Nucleic Acids Res"},{"issue":"13","key":"3801_CR6","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1093\/bioinformatics\/bts251","volume":"28","author":"X Jiao","year":"2012","unstructured":"Jiao X, Sherman BT, Huang DW, Stephens R, Baseler MW, Lane HC, Lempicki RA. DAVID-WS: a stateful web service to facilitate gene\/protein list analysis. Bioinformatics. 2012;28(13):1805\u20136.","journal-title":"Bioinformatics"},{"key":"3801_CR7","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1103\/RevModPhys.74.47","volume":"74","author":"R Albert","year":"2002","unstructured":"Albert R, Barab\u00e1si A-L. Statistical mechanics of complex networks. Rev Mod Phys. 2002;74:47\u201397.","journal-title":"Rev Mod Phys"},{"issue":"suppl\u20132","key":"3801_CR8","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1093\/nar\/gkq537","volume":"38","author":"D Warde-Farley","year":"2010","unstructured":"Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, Franz M, Grouios C, Kazi F, Lopes CT, et al. The genemania prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010;38(suppl\u20132):214\u201320.","journal-title":"Nucleic Acids Res"},{"issue":"suppl\u20132","key":"3801_CR9","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1093\/nar\/gkp427","volume":"37","author":"J Chen","year":"2009","unstructured":"Chen J, Bardes EE, Aronow BJ, Jegga AG. Toppgene suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 2009;37(suppl\u20132):305\u201311.","journal-title":"Nucleic Acids Res"},{"issue":"18","key":"3801_CR10","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1093\/bioinformatics\/bts389","volume":"28","author":"E Glaab","year":"2012","unstructured":"Glaab E, Baudot A, Krasnogor N, Schneider R, Valencia A. Enrichnet: network-based gene set enrichment analysis. Bioinformatics. 2012;28(18):451\u20137.","journal-title":"Bioinformatics"},{"issue":"2","key":"3801_CR11","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/ng.3168","volume":"47","author":"MDM Leiserson","year":"2015","unstructured":"Leiserson MDM, Vandin F, Wu HT, Dobson JR, Eldridge JV, Thomas JL, Papoutsaki A, Kim Y, Niu B, McLellan M, Lawrence MS, Gonzalez-Perez A, Tamborero D, Cheng Y, Ryslik GA, Lopez-Bigas N, Getz G, Ding L, Raphael BJ. Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes. Nat Genet. 2015;47(2):106\u201314.","journal-title":"Nat Genet"},{"issue":"21","key":"3801_CR12","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1093\/bioinformatics\/btt471","volume":"29","author":"EO Paull","year":"2013","unstructured":"Paull EO, Carlin DE, Niepel M, Sorger PK, Haussler D, Stuart JM. Discovering causal pathways linking genomic events to transcriptional states using tied diffusion through interacting events (tiedie). Bioinformatics. 2013;29(21):2757\u201364.","journal-title":"Bioinformatics"},{"issue":"1","key":"3801_CR13","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/s13059-016-0989-x","volume":"17","author":"A Cho","year":"2016","unstructured":"Cho A, Shim JE, Kim E, Supek F, Lehner B, Lee I. Muffinn: cancer gene discovery via network analysis of somatic mutation data. Genome Biol. 2016;17(1):129.","journal-title":"Genome Biol"},{"issue":"9","key":"3801_CR14","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/s41592-019-0509-5","volume":"16","author":"S Choobdar","year":"2019","unstructured":"Choobdar S, Ahsen ME, Crawford J, Tomasoni M, Fang T, Lamparter D, Lin J, Hescott B, Hu X, Mercer J, et al. Assessment of network module identification across complex diseases. Nat Methods. 2019;16(9):843\u201352.","journal-title":"Nat Methods"},{"issue":"1A","key":"3801_CR15","first-page":"68","volume":"19","author":"K Tomczak","year":"2015","unstructured":"Tomczak K, Czerwi\u0144ska P, Wiznerowicz M. The cancer genome atlas (tcga): an immeasurable source of knowledge. Contemp Oncol. 2015;19(1A):68.","journal-title":"Contemp Oncol"},{"issue":"19","key":"3801_CR16","doi-asserted-by":"publisher","first-page":"2520","DOI":"10.1093\/bioinformatics\/bts480","volume":"28","author":"J K\u00f6ster","year":"2012","unstructured":"K\u00f6ster J, Rahmann S. Snakemake\u2013a scalable bioinformatics workflow engine. Bioinformatics. 2012;28(19):2520\u20132.","journal-title":"Bioinformatics"},{"key":"3801_CR17","doi-asserted-by":"publisher","DOI":"10.1093\/oso\/9780198805090.001.0001","volume-title":"Networks","author":"M Newman","year":"2018","unstructured":"Newman M. Networks. Oxford: Oxford University Press; 2018."},{"key":"3801_CR18","unstructured":"Page L, Brin S, Motwani R, Winograd T. The pagerank citation ranking: Bringing order to the web. Technical report, Stanford InfoLab 1999."},{"issue":"1","key":"3801_CR19","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nrg2918","volume":"12","author":"A-L Barab\u00e1si","year":"2011","unstructured":"Barab\u00e1si A-L, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nat Rev Genet. 2011;12(1):56\u201368.","journal-title":"Nat Rev Genet"},{"issue":"9","key":"3801_CR20","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nrg.2017.38","volume":"18","author":"L Cowen","year":"2017","unstructured":"Cowen L, Ideker T, Raphael BJ, Sharan R. Network propagation: a universal amplifier of genetic associations. Nat Rev Genet. 2017;18(9):551\u201362.","journal-title":"Nat Rev Genet"},{"issue":"6224","key":"3801_CR21","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1126\/science.1257601","volume":"347","author":"J Menche","year":"2015","unstructured":"Menche J, Sharma A, Kitsak M, Ghiassian SD, Vidal M, Loscalzo J, Barab\u00e1si AL. Uncovering disease-disease relationships through the incomplete interactome. Science. 2015;347(6224):841.","journal-title":"Science"},{"key":"3801_CR22","doi-asserted-by":"crossref","unstructured":"Ghasemian A, Hosseinmardi H, Clauset A. Evaluating overfit and underfit in models of network community structure. IEEE Transactions on Knowledge and Data Engineering. 2019;.","DOI":"10.1109\/TKDE.2019.2911585"},{"issue":"550","key":"3801_CR23","first-page":"10","volume":"15","author":"M Love","year":"2014","unstructured":"Love M, Anders S, Huber W. Differential analysis of count data-the deseq2 package. Genome Biol. 2014;15(550):10\u20131186.","journal-title":"Genome Biol"},{"key":"3801_CR24","unstructured":"Team PD. PyTables: Hierarchical Datasets in Python (2002). http:\/\/www.pytables.org\/"},{"issue":"3","key":"3801_CR25","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1093\/bioinformatics\/btq675","volume":"27","author":"ME Smoot","year":"2010","unstructured":"Smoot ME, Ono K, Ruscheinski J, Wang P-L, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2010;27(3):431\u20132.","journal-title":"Bioinformatics"},{"issue":"8","key":"3801_CR26","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1093\/nar\/gkv1507","volume":"44","author":"A Colaprico","year":"2015","unstructured":"Colaprico A, Silva TC, Olsen C, Garofano L, Cava C, Garolini D, Sabedot TS, Malta TM, Pagnotta SM, Castiglioni I, et al. Tcgabiolinks: an r\/bioconductor package for integrative analysis of tcga data. Nucleic Acids Res. 2015;44(8):71.","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"3801_CR27","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/ng.2653","volume":"45","author":"J Lonsdale","year":"2013","unstructured":"Lonsdale J, Thomas J, Salvatore M, Phillips R, Lo E, Shad S, Hasz R, Walters G, Garcia F, Young N, et al. The genotype-tissue expression (gtex) project. Nat Genet. 2013;45(6):580\u20135.","journal-title":"Nat Genet"},{"key":"3801_CR28","doi-asserted-by":"crossref","unstructured":"Collado-Torres L, Nellore A, Jaffe AE. recount workflow: accessing over 70,000 human rna-seq samples with bioconductor. F1000Research 6 (2017)","DOI":"10.12688\/f1000research.12223.1"},{"issue":"D1","key":"3801_CR29","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1093\/nar\/gkw1102","volume":"45","author":"A Chatr-Aryamontri","year":"2017","unstructured":"Chatr-Aryamontri A, Oughtred R, Boucher L, Rust J, Chang C, Kolas NK, O\u2019Donnell L, Oster S, Theesfeld C, Sellam A, et al. The biogrid interaction database: 2017 update. Nucleic Acids Res. 2017;45(D1):369\u201379.","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"3801_CR30","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.cell.2018.03.022","volume":"173","author":"KA Hoadley","year":"2018","unstructured":"Hoadley KA, Yau C, Hinoue T, Wolf DM, Lazar AJ, Drill E, Shen R, Taylor AM, Cherniack AD, Thorsson V, et al. Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell. 2018;173(2):291\u2013304.","journal-title":"Cell"},{"issue":"9","key":"3801_CR31","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1093\/bioinformatics\/btq131","volume":"26","author":"E Glaab","year":"2010","unstructured":"Glaab E, Baudot A, Krasnogor N, Valencia A. Topogsa: network topological gene set analysis. Bioinformatics. 2010;26(9):1271\u20132.","journal-title":"Bioinformatics"},{"issue":"4","key":"3801_CR32","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1038\/nprot.2012.004","volume":"7","author":"NT Doncheva","year":"2012","unstructured":"Doncheva NT, Assenov Y, Domingues FS, Albrecht M. Topological analysis and interactive visualization of biological networks and protein structures. Nat Protoc. 2012;7(4):670\u201385.","journal-title":"Nat Protoc"},{"issue":"43","key":"3801_CR33","first-page":"15545","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Genetics. 2005;102(43):15545\u201350.","journal-title":"Genetics"},{"issue":"W1","key":"3801_CR34","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1093\/nar\/gkz401","volume":"47","author":"Y Liao","year":"2019","unstructured":"Liao Y, Wang J, Jaehnig EJ, Shi Z, Zhang B. WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res. 2019;47(W1):199\u2013205.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"3801_CR35","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1186\/1471-2105-13-226","volume":"13","author":"A Alexeyenko","year":"2012","unstructured":"Alexeyenko A, Lee W, Pernemalm M, Guegan J, Dessen P, Lazar V, Lehti\u00f6 J, Pawitan Y. Network enrichment analysis: extension of gene-set enrichment analysis to gene networks. BMC Bioinform. 2012;13(1):226.","journal-title":"BMC Bioinform"},{"issue":"7","key":"3801_CR36","doi-asserted-by":"publisher","first-page":"2118","DOI":"10.1039\/c1mb05014a","volume":"7","author":"B Zhang","year":"2011","unstructured":"Zhang B, Shi Z, Duncan DT, Prodduturi N, Marnett LJ, Liebler DC. Relating protein adduction to gene expression changes: a systems approach. Mol BioSyst. 2011;7(7):2118\u201327.","journal-title":"Mol BioSyst"},{"key":"3801_CR37","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s12859-017-1534-y","volume":"18","author":"A Jeggari","year":"2017","unstructured":"Jeggari A, Alexeyenko A. NEArender: an R package for functional interpretation of \u2019omics\u2019 data via network enrichment analysis. BMC Bioinform. 2017;18:118.","journal-title":"BMC Bioinform"},{"issue":"W1","key":"3801_CR38","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1093\/nar\/gky485","volume":"46","author":"A Jeggari","year":"2018","unstructured":"Jeggari A, Alekseenko Z, Petrov I, Dias JM, Ericson J, Alexeyenko A. EviNet: a web platform for network enrichment analysis with flexible definition of gene sets. Nucleic Acids Res. 2018;46(W1):163\u201370.","journal-title":"Nucleic Acids Res"},{"key":"3801_CR39","doi-asserted-by":"publisher","first-page":"6994","DOI":"10.7717\/peerj.6994","volume":"7","author":"MT Zimmermann","year":"2019","unstructured":"Zimmermann MT, Kabat B, Grill DE, Kennedy RB, Poland GA. Ritan: rapid integration of term annotation and network resources. PeerJ. 2019;7:6994.","journal-title":"PeerJ"},{"issue":"4","key":"3801_CR40","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1093\/molbev\/msn023","volume":"25","author":"G Lima-Mendez","year":"2008","unstructured":"Lima-Mendez G, Van Helden J, Toussaint A, Leplae R. Reticulate representation of evolutionary and functional relationships between phage genomes. Mol Biol Evol. 2008;25(4):762\u201377.","journal-title":"Mol Biol Evol"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-020-03801-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12859-020-03801-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-020-03801-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T19:07:19Z","timestamp":1634843239000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-020-03801-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,22]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["3801"],"URL":"https:\/\/doi.org\/10.1186\/s12859-020-03801-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/699926","asserted-by":"object"}]},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,22]]},"assertion":[{"value":"11 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not Applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"476"}}