{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T05:06:49Z","timestamp":1773551209649,"version":"3.50.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T00:00:00Z","timestamp":1642204800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T00:00:00Z","timestamp":1642204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Ministerio de Ciencia, Innovaci\u00edn y Universidades","award":["SAF2016-78041-C2-1-R"],"award-info":[{"award-number":["SAF2016-78041-C2-1-R"]}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00edn y Universidades","doi-asserted-by":"publisher","award":["PID2019-108096RB-C21"],"award-info":[{"award-number":["PID2019-108096RB-C21"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["UMA18-FEDERJA-102"],"award-info":[{"award-number":["UMA18-FEDERJA-102"]}],"id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00edn Ram\u00edn Areces"},{"DOI":"10.13039\/100009473","name":"Universidad de M\u00edlaga","doi-asserted-by":"publisher","award":["I Ayudas del Plan Propio, D.2"],"award-info":[{"award-number":["I Ayudas del Plan Propio, D.2"]}],"id":[{"id":"10.13039\/100009473","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["PI-0075-2017"],"award-info":[{"award-number":["PI-0075-2017"]}],"id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00edn y Universidades","doi-asserted-by":"publisher","award":["PID2019-105010RB-I00"],"award-info":[{"award-number":["PID2019-105010RB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Junta de Andalucia","award":["PAIDI 2020:PY20-00372"],"award-info":[{"award-number":["PAIDI 2020:PY20-00372"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Protein function prediction remains a key challenge. Domain composition affects protein function. Here we present DomFun, a Ruby gem that uses associations between protein domains and functions, calculated using multiple indices based on tripartite network analysis. These domain-function associations are combined at the protein level, to generate protein-function predictions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We analysed 16 tripartite networks connecting homologous superfamily and FunFam domains from CATH-Gene3D with functional annotations from the three Gene Ontology (GO) sub-ontologies, KEGG, and Reactome. We validated the results using the CAFA 3 benchmark platform for GO annotation, finding that out of the multiple association metrics and domain datasets tested, Simpson index for FunFam domain-function associations combined with Stouffer\u2019s method leads to the best performance in almost all scenarios. We also found that using FunFams led to better performance than superfamilies, and better results were found for GO molecular function compared to GO biological process terms. DomFun performed as well as the highest-performing method in certain CAFA 3 evaluation procedures in terms of <jats:inline-formula><jats:alternatives><jats:tex-math>$$F_{max}$$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                    <mml:msub>\n                      <mml:mi>F<\/mml:mi>\n                      <mml:mrow>\n                        <mml:mi>max<\/mml:mi>\n                      <\/mml:mrow>\n                    <\/mml:msub>\n                  <\/mml:math><\/jats:alternatives><\/jats:inline-formula> and <jats:inline-formula><jats:alternatives><jats:tex-math>$$S_{min}$$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                    <mml:msub>\n                      <mml:mi>S<\/mml:mi>\n                      <mml:mrow>\n                        <mml:mi>min<\/mml:mi>\n                      <\/mml:mrow>\n                    <\/mml:msub>\n                  <\/mml:math><\/jats:alternatives><\/jats:inline-formula> We also implemented our own benchmark procedure, Pathway Prediction Performance (PPP), which can be used to validate function prediction for additional annotations sources, such as KEGG and Reactome. Using PPP, we found similar results to those found with CAFA 3 for GO, moreover we found good performance for the other annotation sources. As with CAFA 3, Simpson index with Stouffer\u2019s method led to the top performance in almost all scenarios.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>DomFun shows competitive performance with other methods evaluated in CAFA 3 when predicting proteins function with GO, although results vary depending on the evaluation procedure. Through our own benchmark procedure, PPP, we have shown it can also make accurate predictions for KEGG and Reactome. It performs best when using FunFams, combining Simpson index derived domain-function associations using Stouffer\u2019s method. The tool has been implemented so that it can be easily adapted to incorporate other protein features, such as domain data from other sources, amino acid k-mers and motifs. The DomFun Ruby gem is available from <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/rubygems.org\/gems\/DomFun\">https:\/\/rubygems.org\/gems\/DomFun<\/jats:ext-link>. Code maintained at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/github.com\/ElenaRojano\/DomFun\">https:\/\/github.com\/ElenaRojano\/DomFun<\/jats:ext-link>. Validation procedure scripts can be found at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/github.com\/ElenaRojano\/DomFun_project\">https:\/\/github.com\/ElenaRojano\/DomFun_project<\/jats:ext-link>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-022-04565-6","type":"journal-article","created":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T22:02:46Z","timestamp":1642284166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Assigning protein function from domain-function associations using DomFun"],"prefix":"10.1186","volume":"23","author":[{"given":"Elena","family":"Rojano","sequence":"first","affiliation":[]},{"given":"Fernando M.","family":"Jabato","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4108-096X","authenticated-orcid":false,"given":"James R.","family":"Perkins","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9","family":"C\u00f3rdoba-Caballero","sequence":"additional","affiliation":[]},{"given":"Federico","family":"Garc\u00eda-Criado","sequence":"additional","affiliation":[]},{"given":"Ian","family":"Sillitoe","sequence":"additional","affiliation":[]},{"given":"Christine","family":"Orengo","sequence":"additional","affiliation":[]},{"given":"Juan A. G.","family":"Ranea","sequence":"additional","affiliation":[]},{"given":"Pedro","family":"Seoane-Zonjic","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,1,15]]},"reference":[{"key":"4565_CR1","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/468773a","volume":"468","author":"FA Rey","year":"2010","unstructured":"Rey FA. One protein, many functions. Nature. 2010;468:773\u20135. https:\/\/doi.org\/10.1038\/468773a.","journal-title":"Nature"},{"issue":"1","key":"4565_CR2","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1146\/annurev.biophys.31.082901.134314","volume":"31","author":"CP Ponting","year":"2002","unstructured":"Ponting CP, Russell RR. The natural history of protein domains. Annu Rev Biophys Biomol Struct. 2002;31(1):45\u201371. https:\/\/doi.org\/10.1146\/annurev.biophys.31.082901.134314.","journal-title":"Annu Rev Biophys Biomol Struct"},{"issue":"15","key":"4565_CR3","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1093\/bioinformatics\/btn312","volume":"24","author":"K Forslund","year":"2008","unstructured":"Forslund K, Sonnhammer ELL. Predicting protein function from domain content. Bioinformatics. 2008;24(15):1681\u20137. https:\/\/doi.org\/10.1093\/bioinformatics\/btn312.","journal-title":"Bioinformatics"},{"key":"4565_CR4","doi-asserted-by":"publisher","unstructured":"Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G. Gene ontology: tool for the unification of biology. 2000. https:\/\/doi.org\/10.1038\/75556.","DOI":"10.1038\/75556"},{"key":"4565_CR5","doi-asserted-by":"publisher","unstructured":"Carbon S, Douglass E, Dunn N, Good B, Harris NL, Lewis SE, Mungall CJ, Basu S, Chisholm RL, Dodson RJ, Hartline E, Fey P, Thomas PD, Albou LP, Ebert D, Kesling MJ, Mi H, Muruganujan A, Huang X, Poudel S, Mushayahama T, Hu JC, LaBonte SA, Siegele DA, Antonazzo G, Attrill H, Brown NH, Fexova S, Garapati P, Jones TEM, Marygold SJ, Millburn GH, Rey AJ, Trovisco V, Dos Santos G, Emmert DB, Falls K, Zhou P, Goodman JL, Strelets VB, Thurmond J, Courtot M, Osumi DS, Parkinson H, Roncaglia P, Acencio ML, Kuiper M, Lreid A, Logie C, Lovering RC, Huntley RP, Denny P, Campbell NH, Kramarz B, Acquaah V, Ahmad SH, Chen H, Rawson JH, Chibucos MC, Giglio M, Nadendla S, Tauber R, Duesbury MJ, Del NT, Meldal BHM, Perfetto L, Porras P, Orchard S, Shrivastava A, Xie Z, Chang HY, Finn RD, Mitchell AL, Rawlings ND, Richardson L, Sangrador-Vegas A, Blake JA, Christie KR, Dolan ME, Drabkin HJ, Hill DP, Ni L, Sitnikov D, Harris MA, Oliver SG, Rutherford K, Wood V, Hayles J, Bahler J, Lock A, Bolton ER, De Pons J, Dwinell M, Hayman GT, Laulederkind SJF, Shimoyama M, Tutaj M, Wang SJ, D\u2019Eustachio P, Matthews L, Balhoff JP, Aleksander SA, Binkley G, Dunn BL, Cherry JM, Engel SR, Gondwe F, Karra K, MacPherson KA, Miyasato SR, Nash RS, Ng PC, Sheppard TK, Shrivatsav Vp A, Simison M, Skrzypek MS, Weng S, Wong ED, Feuermann M, Gaudet P, Bakker E, Berardini TZ, Reiser L, Subramaniam S, Huala E, Arighi C, Auchincloss A, Axelsen K, Argoud GP, Bateman A, Bely B, Blatter MC, Boutet E, Breuza L, Bridge A, Britto R, Bye-A-Jee H, Casals-Casas C, Coudert E, Estreicher A, Famiglietti L, Garmiri P, Georghiou G, Gos A, Gruaz-Gumowski N, Hatton-Ellis E, Hinz U, Hulo C, Ignatchenko A, Jungo F, Keller G, Laiho K, Lemercier P, Lieberherr D, Lussi Y, Mac-Dougall A, Magrane M, Martin MJ, Masson P, Natale DA, Hyka NN, Pedruzzi I, Pichler K, Poux S, Rivoire C, Rodriguez-Lopez M, Sawford T, Speretta E, Shypitsyna A, Stutz A, Sundaram S, Tognolli M, Tyagi N, Warner K, Zaru R, Wu C, Chan J, Cho J, Gao S, Grove C, Harrison MC, Howe K, Lee R, Mendel J, Muller HM, Raciti D, Van Auken K, Berriman M, Stein L, Sternberg PW, Howe D, Toro S, Westerfield M. The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Res (2019). https:\/\/doi.org\/10.1093\/nar\/gky1055","DOI":"10.1093\/nar\/gky1055"},{"key":"4565_CR6","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1080","author":"H Fang","year":"2013","unstructured":"Fang H, Gough J. DcGO: database of domain-centric ontologies on functions, phenotypes, diseases and more. Nucleic Acids Res. 2013. https:\/\/doi.org\/10.1093\/nar\/gks1080.","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"4565_CR7","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1016\/s0969-2126(97)00260-8","volume":"5","author":"CA Orengo","year":"1997","unstructured":"Orengo CA, Michie AD, Jones S, Jones DT, Swindells MB, Thornton JM. CATH\u2014a hierarchic classification of protein domain structures. Structure. 1997;5(8):1093\u2013108. https:\/\/doi.org\/10.1016\/s0969-2126(97)00260-8.","journal-title":"Structure"},{"issue":"Database issue","key":"4565_CR8","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1093\/nar\/gku947","volume":"43","author":"I Sillitoe","year":"2015","unstructured":"Sillitoe I, Lewis TE, Cuff A, Das S, Ashford P, Dawson NL, Furnham N, Laskowski RA, Lee D, Lees JG, Lehtinen S, Studer RA, Thornton J, Orengo CA. CATH: comprehensive structural and functional annotations for genome sequences. Nucleic Acids Res. 2015;43(Database issue):376\u201381. https:\/\/doi.org\/10.1093\/nar\/gku947.","journal-title":"Nucleic Acids Res"},{"issue":"Web server issu","key":"4565_CR9","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1093\/nar\/gkv488","volume":"43","author":"S Das","year":"2015","unstructured":"Das S, Sillitoe I, Lee D, Lees JG, Dawson NL, Ward J, Orengo CA. CATH FunFHMMer web server: protein functional annotations using functional family assignments. Nucleic Acids Res. 2015;43(Web server issue):148\u201353. https:\/\/doi.org\/10.1093\/nar\/gkv488.","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"4565_CR10","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1093\/nar\/gkw1098","volume":"45","author":"NL Dawson","year":"2017","unstructured":"Dawson NL, Lewis TE, Das S, Lees JG, Lee D, Ashford P, Orengo CA, Sillitoe I. CATH: an expanded resource to predict protein function through structure and sequence. Nucleic Acids Res. 2017;45(D1):289\u201395. https:\/\/doi.org\/10.1093\/nar\/gkw1098.","journal-title":"Nucleic Acids Res"},{"issue":"400","key":"4565_CR11","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12859-019-2988-x","volume":"20","author":"L Scheibenreif","year":"2019","unstructured":"Scheibenreif L, Littmann M, Orengo C, Rost B. FunFam protein families improve residue level molecular function prediction. BMC Bioinform. 2019;20(400):66. https:\/\/doi.org\/10.1186\/s12859-019-2988-x.","journal-title":"BMC Bioinform"},{"key":"4565_CR12","doi-asserted-by":"crossref","unstructured":"Rojano E, Seoane P, Bueno-Amoros A, Perkins JR, Garcia-Ranea JA. Revealing the relationship between human genome regions and pathological phenotypes through network analysis. In: Rojas I, Ortu\u00f1o F (eds) International conference on bioinformatics and biomedical engineering: 5th international work conference, IWBBIO 2017, Granada, Spain: Springer; 2017. p. 197\u2013207.","DOI":"10.1007\/978-3-319-56148-6_17"},{"key":"4565_CR13","doi-asserted-by":"publisher","unstructured":"Jabato FM, Rojano E, Perkins JR, Ranea JAG, Seoane-Zonjic P. Kernel based approaches to identify hidden connections in gene networks using NetAnalyzer. In: Lecture notes in computer science (including subseries lecture notes in artificial intelligence and lecture notes in bioinformatics) (2020). https:\/\/doi.org\/10.1007\/978-3-030-45385-5_68.","DOI":"10.1007\/978-3-030-45385-5_68"},{"issue":"1","key":"4565_CR14","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/s12864-016-2569-6","volume":"17","author":"A Reyes-Palomares","year":"2016","unstructured":"Reyes-Palomares A, Bueno A, Rodr\u00edguez-L\u00f3pez R, Medina M\u00c1, S\u00e1nchez-Jim\u00e9nez F, Corpas M, Ranea JAGG. Systematic identification of phenotypically enriched loci using a patient network of genomic disorders. BMC Genomics. 2016;17(1):232. https:\/\/doi.org\/10.1186\/s12864-016-2569-6.","journal-title":"BMC Genomics"},{"key":"4565_CR15","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1038\/s41431-018-0139-x","volume":"26","author":"A Bueno","year":"2018","unstructured":"Bueno A, Rodr\u00edguez-L\u00f3pez R, Reyes-Palomares A, Rojano E, Corpas M, Nevado J, Lapunzina P, S\u00e1nchez-Jim\u00e9nez F, Ranea JAGG. Phenotype-loci associations in networks of patients with rare disorders: application to assist in the diagnosis of novel clinical cases. Eur J Hum Genet. 2018;26:1451\u201361. https:\/\/doi.org\/10.1038\/s41431-018-0139-x.","journal-title":"Eur J Hum Genet"},{"key":"4565_CR16","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s00439-020-02214-7","volume":"6","author":"FM Jabato","year":"2020","unstructured":"Jabato FM, Seoane P, Perkins JR, Rojano E, Garc\u00eda Moreno A, Chagoyen M, Pazos F, Ranea JAG. Systematic identification of genetic systems associated with phenotypes in patients with rare genomic copy number variations. Human Genet. 2020;6:66. https:\/\/doi.org\/10.1007\/s00439-020-02214-7.","journal-title":"Human Genet"},{"issue":"10","key":"4565_CR17","doi-asserted-by":"publisher","first-page":"1009054","DOI":"10.1371\/journal.pgen.1009054","volume":"16","author":"E D\u00edaz-Santiago","year":"2020","unstructured":"D\u00edaz-Santiago E, Jabato FM, Rojano E, Seoane P, Pazos F, Perkins JR, Ranea JAG. Phenotype-genotype comorbidity analysis of patients with rare disorders provides insight into their pathological and molecular bases. PLOS Genet. 2020;16(10):1009054.","journal-title":"PLOS Genet"},{"key":"4565_CR18","doi-asserted-by":"publisher","unstructured":"Rojano E, Seoane-Zonjic P, Jabato FM, Perkins JR, Ranea JAG. Comprehensive analysis of patients with undiagnosed genetic diseases using the Patient Exploration Tools Suite (PETS). In: Lecture notes in computer science (including subseries lecture notes in artificial intelligence and lecture notes in bioinformatics). 2020. https:\/\/doi.org\/10.1007\/978-3-030-45385-5_69","DOI":"10.1007\/978-3-030-45385-5_69"},{"key":"4565_CR19","doi-asserted-by":"publisher","unstructured":"Rojano E, Perkins JR, Sillitoe I, Orengo C, Garc\u00eda Ranea JA, Seoane P. Associating protein domains with biological functions: a tripartite network approach. In: Lecture notes in computer science (including subseries lecture notes in artificial intelligence and lecture notes in bioinformatics). 2019. p. 155\u201364. https:\/\/doi.org\/10.1007\/978-3-030-17935-9_15.","DOI":"10.1007\/978-3-030-17935-9_15"},{"key":"4565_CR20","doi-asserted-by":"publisher","unstructured":"Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, Kanehisa M. KEGG: Kyoto encyclopedia of genes and genomes. 1999. arXiv:1011.1669v3. https:\/\/doi.org\/10.1093\/nar\/27.1.29.","DOI":"10.1093\/nar\/27.1.29"},{"key":"4565_CR21","doi-asserted-by":"publisher","unstructured":"Fabregat A, Jupe S, Matthews L, Sidiropoulos K, Gillespie M, Garapati P, Haw R, Jassal B, Korninger F, May B, Milacic M, Roca CD, Rothfels K, Sevilla C, Shamovsky V, Shorser S, Varusai T, Viteri G, Weiser J, Wu G, Stein L, Hermjakob H, D\u2019Eustachio P. The Reactome pathway knowledgebase. Nucleic Acids Res. 2018;44(Database issue):481\u20137. https:\/\/doi.org\/10.1093\/nar\/gkx1132.","DOI":"10.1093\/nar\/gkx1132"},{"key":"4565_CR22","doi-asserted-by":"publisher","unstructured":"Zhou N, Jiang Y, Bergquist TR, Lee AJ, Kacsoh BZ, Crocker AW, Lewis KA, Georghiou G, Nguyen HN, Hamid MN, Davis L, Dogan T, Atalay V, Rifaioglu AS, Dalkiran A, Cetin-Atalay R, Zhang C, Hurto RL, Freddolino PL, Zhang Y, Bhat P, Supek F, Fern\u00e1ndez JM., Gemovic B, Perovic VR, Davidovi\u0107 RS, Sumonja N, Veljkovic N, Asgari E, Mofrad MR, Profiti G, Savojardo C, Martelli PL, Casadio R, Boecker F, Kahanda I, Thurlby N, McHardy AC, Renaux A, Saidi R, Gough J, Freitas AA, Antczak M, Fabris F, Wass MN, Hou J, Cheng J, Hou J, Wang Z, Romero AE, Paccanaro A, Yang H, Goldberg T, Zhao C, Holm L, T\u00f6r\u00f6nen P, Medlar AJ, Zosa E, Borukhov I, Novikov I, Wilkins A, Lichtarge O, Chi P-H, Tseng W-C, Linial M, Rose PW, Dessimoz C, Vidulin V, Dzeroski S, Sillitoe I, Das S, Lees JG, Jones DT, Wan C, Cozzetto D, Fa R, Torres M, Vesztrocy AW, Rodriguez JM, Tress ML, Frasca M, Notaro M, Grossi G, Petrini A, Re M, Valentini G, Mesiti M, Roche DB, Reeb J, Ritchie DW, Aridhi S, Alborzi SZ, Devignes M-D, Koo DCE, Bonneau R, Gligorijevi\u0107 V, Barot M, Fang H, Toppo S, Lavezzo E, Falda M, Berselli M, Tosatto SC, Carraro M, Piovesan D, Rehman HU, Mao Q, Zhang S, Vucetic S, Black GS, Jo D, Larsen DJ, Omdahl AR, Sagers LW, Suh E, Dayton JB, McGuffin LJ, Brackenridge DA, Babbitt PC, Yunes JM, Fontana P, Zhang F, Zhu S, You R, Zhang Z, Dai S, Yao S, Tian W, Cao R, Chandler C, Amezola M, Johnson D, Chang J-M, Liao W-H, Liu Y-W, Pascarelli S, Frank Y, Hoehndorf R, Kulmanov M, Boudellioua I, Politano G, Carlo SD, Benso A, Hakala K, Ginter F, Mehryary F, Kaewphan S, Bj\u00f6rne J, Moen H, Tolvanen MEE, Salakoski T, Kihara D, Jain A, \u0160muc T, Altenhoff A, Ben-Hur A, Rost B, Brenner SE, Orengo CA, Jeffery CJ, Bosco G, Hogan DA, Martin MJ, O\u2019Donovan C, Mooney SD, Greene CS, Radivojac P, Friedberg I. The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens. Genome Biol. 2019. https:\/\/doi.org\/10.1101\/653105.","DOI":"10.1101\/653105"},{"key":"4565_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-S3-S5","author":"R Rentzsch","year":"2013","unstructured":"Rentzsch R, Orengo CA. Protein function prediction using domain families. BMC Bioinform. 2013. https:\/\/doi.org\/10.1186\/1471-2105-14-S3-S5.","journal-title":"BMC Bioinform"},{"issue":"12","key":"4565_CR24","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1038\/nmeth.2728","volume":"10","author":"JIF Bass","year":"2013","unstructured":"Bass JIF, Diallo A, Nelson J, Soto JM, Myers CL, Walhout AJM. Using networks to measure similarity between genes: association index selection. Nat Methods. 2013;10(12):1169\u201376. https:\/\/doi.org\/10.1038\/nmeth.2728.","journal-title":"Nat Methods"},{"key":"4565_CR25","unstructured":"Stouffer SA, Suchman EA, Devinney LC, Star SA., Williams RM, Jr. The American Soldier: adjustment during army life. Studies in Social Psychology in World War II, vol 1; 1949."},{"key":"4565_CR26","doi-asserted-by":"publisher","unstructured":"Jiang Y, Oron TR, Clark WT, Bankapur AR, D\u2019Andrea D, Lepore R, Funk CS, Kahanda I, Verspoor KM, Ben-Hur A, Koo DCE, Penfold-Brown D, Shasha D, Youngs N, Bonneau R, Lin A, Sahraeian SME, Martelli PL, Profiti G, Casadio R, Cao R, Zhong Z, Cheng J, Altenhoff A, Skunca N, Dessimoz C, Dogan T, Hakala K, Kaewphan S, Mehryary F, Salakoski T, Ginter F, Fang H, Smithers B, Oates M, Gough J, T\u00f6r\u00f6nen P, Koskinen P, Holm L, Chen CT, Hsu WL, Bryson K, Cozzetto D, Minneci F, Jones DT, Chapman S, Bkc D, Khan IK, Kihara D, Ofer D, Rappoport N, Stern A, Cibrian-Uhalte E, Denny P, Foulger RE, Hieta R, Legge D, Lovering RC, Magrane M, Melidoni AN, Mutowo-Meullenet P, Pichler K, Shypitsyna A, Li B, Zakeri P, ElShal S, Tranchevent LC, Das S, Dawson NL, Lee D, Lees JG, Sillitoe I, Bhat P, Nepusz T, Romero AE, Sasidharan R, Yang H, Paccanaro A, Gillis J, Sede\u00f1o-Cort\u00e9s AE, Pavlidis P, Feng S, Cejuela JM, Goldberg T, Hamp T, Richter L, Salamov A, Gabaldon T, Marcet-Houben M, Supek F, Gong Q, Ning W, Zhou Y, Tian W, Falda M, Fontana P, Lavezzo E, Toppo S, Ferrari C, Giollo M, Piovesan D, Tosatto SCE, del Pozo A, Fern\u00e1ndez JM, Maietta P, Valencia A, Tress ML, Benso A, Di Carlo S, Politano G, Savino A, Rehman HU, Re M, Mesiti M, Valentini G, Bargsten JW, van Dijk ADJ, Gemovic B, Glisic S, Perovic V, Veljkovic V, Veljkovic N, Almeida-e-Silva DC, Vencio RZN, Sharan M, Vogel J, Kansakar L, Zhang S, Vucetic S, Wang Z, Sternberg MJE, Wass MN, Huntley RP, Martin MJ, O\u2019Donovan C, Robinson PN, Moreau Y, Tramontano A, Babbitt PC, Brenner SE, Linial M, Orengo CA, Rost B, Greene CS, Mooney SD, Friedberg I, Radivojac P. An expanded evaluation of protein function prediction methods shows an improvement in accuracy. Genome Biol. 2016;17(1):184. https:\/\/doi.org\/10.1186\/s13059-016-1037-6.1601.00891.","DOI":"10.1186\/s13059-016-1037-6.1601.00891"},{"issue":"3","key":"4565_CR27","doi-asserted-by":"publisher","first-page":"241","DOI":"10.2307\/1266041","volume":"6","author":"OJ Dunn","year":"1964","unstructured":"Dunn OJ. Multiple comparisons using rank sums. Technometrics. 1964;6(3):241. https:\/\/doi.org\/10.2307\/1266041.","journal-title":"Technometrics"},{"issue":"20","key":"4565_CR28","doi-asserted-by":"publisher","first-page":"3940","DOI":"10.1093\/bioinformatics\/bti623","volume":"21","author":"T Sing","year":"2005","unstructured":"Sing T, Sander O, Beerenwinkel N, Lengauer T. ROCR: visualizing classifier performance in R. Bioinformatics. 2005;21(20):3940\u20131. https:\/\/doi.org\/10.1093\/bioinformatics\/bti623.","journal-title":"Bioinformatics"},{"key":"4565_CR29","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv398","author":"S Das","year":"2015","unstructured":"Das S, Lee D, Sillitoe I, Dawson NL, Lees JG, Orengo CA. Functional classification of CATH superfamilies: a domain-based approach for protein function annotation. Bioinformatics. 2015. https:\/\/doi.org\/10.1093\/bioinformatics\/btv398.","journal-title":"Bioinformatics"},{"key":"4565_CR30","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1155\/2014\/363408","volume":"6","author":"T Clancy","year":"2014","unstructured":"Clancy T, Hovig E. Differential protein network analysis of the immune cell lineage. BioMed Res Int. 2014;6:66. https:\/\/doi.org\/10.1155\/2014\/363408.","journal-title":"BioMed Res Int"},{"issue":"68","key":"4565_CR31","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/1471-2105-14-68","volume":"14","author":"JA Jaramillo-Garz\u00f3n","year":"2013","unstructured":"Jaramillo-Garz\u00f3n JA, Gallardo-Chac\u00f3n JJ, Castellanos-Dom\u00ednguez CG, Perera-Lluna A. Predictability of gene ontology slim-terms from primary structure information in Embryophyta plant proteins. BMC Bioinform. 2013;14(68):66. https:\/\/doi.org\/10.1186\/1471-2105-14-68.","journal-title":"BMC Bioinform"},{"issue":"3","key":"4565_CR32","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.ygeno.2018.02.008","volume":"111","author":"Y Zhao","year":"2019","unstructured":"Zhao Y, Fu G, Wang J, Guo M, Yu G. Gene function prediction based on Gene Ontology hierarchy preserving hashing. Genomics. 2019;111(3):334\u201342. https:\/\/doi.org\/10.1016\/j.ygeno.2018.02.008.","journal-title":"Genomics"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-022-04565-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12859-022-04565-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-022-04565-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T22:03:02Z","timestamp":1642284182000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-022-04565-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,15]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["4565"],"URL":"https:\/\/doi.org\/10.1186\/s12859-022-04565-6","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,15]]},"assertion":[{"value":"5 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43"}}