{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T04:09:52Z","timestamp":1775880592885,"version":"3.50.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Biological signaling pathways that govern cellular physiology form an intricate web of tightly regulated interlocking processes. Data on these regulatory networks are accumulating at an unprecedented pace. The assimilation, visualization and interpretation of these data have become a major challenge in biological research, and once met, will greatly boost our ability to understand cell functioning on a systems level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>To cope with this challenge, we are developing the SPIKE knowledge-base of signaling pathways. SPIKE contains three main software components: 1) A database (DB) of biological signaling pathways. Carefully curated information from the literature and data from large public sources constitute distinct tiers of the DB. 2) A visualization package that allows interactive graphic representations of regulatory interactions stored in the DB and superposition of functional genomic and proteomic data on the maps. 3) An algorithmic inference engine that analyzes the networks for novel functional interplays between network components.<\/jats:p><jats:p>SPIKE is designed and implemented as a community tool and therefore provides a user-friendly interface that allows registered users to upload data to SPIKE DB. Our vision is that the DB will be populated by a distributed and highly collaborative effort undertaken by multiple groups in the research community, where each group contributes data in its field of expertise.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The integrated capabilities of SPIKE make it a powerful platform for the analysis of signaling networks and the integration of knowledge on such networks with<jats:italic>omics<\/jats:italic>data.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2105-9-110","type":"journal-article","created":{"date-parts":[[2008,2,21]],"date-time":"2008-02-21T07:13:13Z","timestamp":1203577993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["SPIKE \u2013 a database, visualization and analysis tool of cellular signaling pathways"],"prefix":"10.1186","volume":"9","author":[{"given":"Ran","family":"Elkon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Vesterman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nira","family":"Amit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Ulitsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Idan","family":"Zohar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mali","family":"Weisz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilad","family":"Mass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nir","family":"Orlev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giora","family":"Sternberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Blekhman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackie","family":"Assa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosef","family":"Shiloh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron","family":"Shamir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2008,2,20]]},"reference":[{"key":"2095_CR1","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1126\/science.298.5594.824","volume":"298","author":"R Milo","year":"2002","unstructured":"Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U: Network motifs: simple building blocks of complex networks. Science 2002, 298: 824\u2013827. 10.1126\/science.298.5594.824","journal-title":"Science"},{"key":"2095_CR2","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/ng881","volume":"31","author":"SS Shen-Orr","year":"2002","unstructured":"Shen-Orr SS, Milo R, Mangan S, Alon U: Network motifs in the transcriptional regulation network of Escherichia coli. Nat Genet 2002, 31: 64\u201368. 10.1038\/ng881","journal-title":"Nat Genet"},{"key":"2095_CR3","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.1126\/science.1064621","volume":"293","author":"PD Karp","year":"2001","unstructured":"Karp PD: Pathway databases: a case study in computational symbolic theories. Science 2001, 293: 2040\u20132044. 10.1126\/science.1064621","journal-title":"Science"},{"key":"2095_CR4","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1093\/nar\/28.1.123","volume":"28","author":"R Overbeek","year":"2000","unstructured":"Overbeek R, Larsen N, Pusch GD, D'Souza M, Selkov E Jr, Kyrpides N, Fonstein M, Maltsev N, Selkov E: WIT: integrated system for high-throughput genome sequence analysis and metabolic reconstruction. Nucleic Acids Res 2000, 28: 123\u2013125. 10.1093\/nar\/28.1.123","journal-title":"Nucleic Acids Res"},{"key":"2095_CR5","doi-asserted-by":"publisher","first-page":"D277","DOI":"10.1093\/nar\/gkh063","volume":"32","author":"M Kanehisa","year":"2004","unstructured":"Kanehisa M, Goto S, Kawashima S, Okuno Y, Hattori M: The KEGG resource for deciphering the genome. Nucleic Acids Res 2004, 32: D277\u2013280. 10.1093\/nar\/gkh063","journal-title":"Nucleic Acids Res"},{"key":"2095_CR6","doi-asserted-by":"publisher","first-page":"D428","DOI":"10.1093\/nar\/gki072","volume":"33","author":"G Joshi-Tope","year":"2005","unstructured":"Joshi-Tope G, Gillespie M, Vastrik I, D'Eustachio P, Schmidt E, de Bono B, Jassal B, Gopinath GR, Wu GR, Matthews L, Lewis S, Birney E, Stein L: Reactome: a knowledgebase of biological pathways. Nucleic Acids Res 2005, 33: D428\u2013432. 10.1093\/nar\/gki072","journal-title":"Nucleic Acids Res"},{"key":"2095_CR7","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1093\/bib\/2.1.81","volume":"2","author":"J van Helden","year":"2001","unstructured":"van Helden J, Naim A, Lemer C, Mancuso R, Eldridge M, Wodak SJ: From molecular activities and processes to biological function. Brief Bioinform 2001, 2: 81\u201393. 10.1093\/bib\/2.1.81","journal-title":"Brief Bioinform"},{"key":"2095_CR8","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1515\/BC.2000.113","volume":"381","author":"J van Helden","year":"2000","unstructured":"van Helden J, Naim A, Mancuso R, Eldridge M, Wernisch L, Gilbert D, Wodak SJ: Representing and analysing molecular and cellular function using the computer. Biol Chem 2000, 381: 921\u2013935. 10.1515\/BC.2000.113","journal-title":"Biol Chem"},{"key":"2095_CR9","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1093\/nar\/gkg056","volume":"31","author":"GD Bader","year":"2003","unstructured":"Bader GD, Betel D, Hogue CW: BIND: the Biomolecular Interaction Network Database. Nucleic Acids Res 2003, 31: 248\u2013250. 10.1093\/nar\/gkg056","journal-title":"Nucleic Acids Res"},{"key":"2095_CR10","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1093\/bioinformatics\/18.7.996","volume":"18","author":"E Demir","year":"2002","unstructured":"Demir E, Babur O, Dogrusoz U, Gursoy A, Nisanci G, Cetin-Atalay R, Ozturk M: PATIKA: an integrated visual environment for collaborative construction and analysis of cellular pathways. Bioinformatics 2002, 18: 996\u20131003. 10.1093\/bioinformatics\/18.7.996","journal-title":"Bioinformatics"},{"key":"2095_CR11","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1038\/nbt1111","volume":"23","author":"H Kitano","year":"2005","unstructured":"Kitano H, Funahashi A, Matsuoka Y, Oda K: Using process diagrams for the graphical representation of biological networks. Nat Biotechnol 2005, 23: 961\u2013966. 10.1038\/nbt1111","journal-title":"Nat Biotechnol"},{"key":"2095_CR12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/ng0502-19","volume":"31","author":"KD Dahlquist","year":"2002","unstructured":"Dahlquist KD, Salomonis N, Vranizan K, Lawlor SC, Conklin BR: GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nat Genet 2002, 31: 19\u201320. 10.1038\/ng0502-19","journal-title":"Nat Genet"},{"key":"2095_CR13","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003, 13: 2498\u20132504. 10.1101\/gr.1239303","journal-title":"Genome Res"},{"key":"2095_CR14","doi-asserted-by":"crossref","first-page":"pe8","DOI":"10.1126\/stke.2222004pe8","volume":"2004","author":"MI Aladjem","year":"2004","unstructured":"Aladjem MI, Pasa S, Parodi S, Weinstein JN, Pommier Y, Kohn KW: Molecular interaction maps\u2013a diagrammatic graphical language for bioregulatory networks. Sci STKE 2004, 2004: pe8.","journal-title":"Sci STKE"},{"key":"2095_CR15","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1063\/1.1338126","volume":"11","author":"KW Kohn","year":"2001","unstructured":"Kohn KW: Molecular interaction maps as information organizers and simulation guides. Chaos 2001, 11: 84\u201397. 10.1063\/1.1338126","journal-title":"Chaos"},{"key":"2095_CR16","doi-asserted-by":"publisher","first-page":"D54","DOI":"10.1093\/nar\/gki031","volume":"33","author":"D Maglott","year":"2005","unstructured":"Maglott D, Ostell J, Pruitt KD, Tatusova T: Entrez Gene: gene-centered information at NCBI. Nucleic Acids Res 2005, 33: D54\u201358. 10.1093\/nar\/gki031","journal-title":"Nucleic Acids Res"},{"key":"2095_CR17","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/sj.embor.embor925","volume":"4","author":"M van den Bosch","year":"2003","unstructured":"van den Bosch M, Bree RT, Lowndes NF: The MRN complex: coordinating and mediating the response to broken chromosomes. EMBO Rep 2003, 4: 844\u2013849. 10.1038\/sj.embor.embor925","journal-title":"EMBO Rep"},{"key":"2095_CR18","unstructured":"ChEBI[http:\/\/www.ebi.ac.uk\/chebi\/]"},{"key":"2095_CR19","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M, Goto S: KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000, 28: 27\u201330. 10.1093\/nar\/28.1.27","journal-title":"Nucleic Acids Res"},{"key":"2095_CR20","doi-asserted-by":"publisher","first-page":"D561","DOI":"10.1093\/nar\/gkl958","volume":"35","author":"S Kerrien","year":"2007","unstructured":"Kerrien S, Alam-Faruque Y, Aranda B, Bancarz I, Bridge A, Derow C, Dimmer E, Feuermann M, Friedrichsen A, Huntley R, Kohler C, Khadake J, Leroy C, Liban A, Lieftink C, Montecchi-Palazzi L, Orchard S, Risse J, Robbe K, Roechert B, Thorneycroft D, Zhang Y, Apweiler R, Hermjakob H: IntAct\u2013open source resource for molecular interaction data. Nucleic Acids Res 2007, 35: D561\u2013565. 10.1093\/nar\/gkl958","journal-title":"Nucleic Acids Res"},{"key":"2095_CR21","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/j.cell.2005.08.029","volume":"122","author":"U Stelzl","year":"2005","unstructured":"Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksoz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE: A human protein-protein interaction network: a resource for annotating the proteome. Cell 2005, 122: 957\u2013968. 10.1016\/j.cell.2005.08.029","journal-title":"Cell"},{"key":"2095_CR22","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1038\/nature04209","volume":"437","author":"JF Rual","year":"2005","unstructured":"Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, et al.: Towards a proteome-scale map of the human protein-protein interaction network. Nature 2005, 437: 1173\u20131178. 10.1038\/nature04209","journal-title":"Nature"},{"key":"2095_CR23","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.cell.2006.03.032","volume":"125","author":"J Lim","year":"2006","unstructured":"Lim J, Hao T, Shaw C, Patel AJ, Szabo G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabasi AL, Vidal M, Zoghbi HY: A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 2006, 125: 801\u2013814. 10.1016\/j.cell.2006.03.032","journal-title":"Cell"},{"key":"2095_CR24","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/msb4100134","volume":"3","author":"RM Ewing","year":"2007","unstructured":"Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, et al.: Large-scale mapping of human protein-protein interactions by mass spectrometry. Mol Syst Biol 2007, 3: 89. 10.1038\/msb4100134","journal-title":"Mol Syst Biol"},{"key":"2095_CR25","unstructured":"BioPAX[http:\/\/www.biopax.org\/]"},{"key":"2095_CR26","unstructured":"SPIKE[http:\/\/www.cs.tau.ac.il\/~spike]"},{"key":"2095_CR27","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.4161\/cc.4.12.2173","volume":"4","author":"C Linhart","year":"2005","unstructured":"Linhart C, Elkon R, Shiloh Y, Shamir R: Deciphering transcriptional regulatory elements that encode specific cell cycle phasing by comparative genomics analysis. Cell Cycle 2005, 4: 1788\u20131797.","journal-title":"Cell Cycle"},{"key":"2095_CR28","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1186\/1471-2164-8-394","volume":"8","author":"R Elkon","year":"2007","unstructured":"Elkon R, Linhart C, Halperin Y, Shiloh Y, Shamir R: Functional genomic delineation of TLR-induced transcriptional networks. BMC Genomics 2007, 8: 394. 10.1186\/1471-2164-8-394","journal-title":"BMC Genomics"},{"key":"2095_CR29","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/1471-2105-6-232","volume":"6","author":"R Shamir","year":"2005","unstructured":"Shamir R, Maron-Katz A, Tanay A, Linhart C, Steinfeld I, Sharan R, Shiloh Y, Elkon R: EXPANDER\u2013an integrative program suite for microarray data analysis. BMC Bioinformatics 2005, 6: 232. 10.1186\/1471-2105-6-232","journal-title":"BMC Bioinformatics"},{"key":"2095_CR30","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1752-0509-1-8","volume":"1","author":"I Ulitsky","year":"2007","unstructured":"Ulitsky I, Shamir R: Identification of functional modules using network topology and high-throughput data. BMC Syst Biol 2007, 1: 8. 10.1186\/1752-0509-1-8","journal-title":"BMC Syst Biol"},{"key":"2095_CR31","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1126\/science.287.5459.1824","volume":"287","author":"A Hirao","year":"2000","unstructured":"Hirao A, Kong YY, Matsuoka S, Wakeham A, Ruland J, Yoshida H, Liu D, Elledge SJ, Mak TW: DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 2000, 287: 1824\u20131827. 10.1126\/science.287.5459.1824","journal-title":"Science"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-9-110.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T15:45:12Z","timestamp":1684251912000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-9-110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,20]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["2095"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-9-110","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2,20]]},"assertion":[{"value":"31 August 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2008","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2008","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"110"}}