{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:24:37Z","timestamp":1778631877913,"version":"3.51.4"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T00:00:00Z","timestamp":1550016000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Korea Centers for Disease Control and Prevention","award":["4845-303"],"award-info":[{"award-number":["4845-303"]}]},{"name":"the National Research Foundation of Korea (NRF) grant funded by the Korea government","award":["2017R1E1A1A03070345"],"award-info":[{"award-number":["2017R1E1A1A03070345"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s12859-019-2638-3","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T10:04:20Z","timestamp":1550052260000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Disease Pathway Cut for Multi-Target drugs"],"prefix":"10.1186","volume":"20","author":[{"given":"Sunjoo","family":"Bang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangjoon","family":"Son","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sooyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8347-8277","authenticated-orcid":false,"given":"Hyunjung","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,2,13]]},"reference":[{"issue":"4","key":"2638_CR1","doi-asserted-by":"publisher","first-page":"e1004219","DOI":"10.1371\/journal.pcbi.1004219","volume":"11","author":"CA Leeuw de","year":"2015","unstructured":"de Leeuw CA, Mooij JM, Heskes T, Posthuma D. MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput Biol. 2015;11(4):e1004219.","journal-title":"PLoS Comput Biol"},{"issue":"3","key":"2638_CR2","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/nmeth.3734","volume":"13","author":"J Fan","year":"2016","unstructured":"Fan J, Salathia N, Liu R, Kaeser GE, Yung YC, Herman JL, Kaper F, Fan J-B, Zhang K, Chun J. Characterizing transcriptional heterogeneity through pathway and gene set overdispersion analysis. Nat Methods. 2016;13(3):241.","journal-title":"Nat Methods"},{"key":"2638_CR3","doi-asserted-by":"crossref","unstructured":"Qu, Pingping, et al. \"An Evaluation of Gene Set Analysis for Biomarker Discovery with Applications to Myeloma Research.\" Frontiers of Biostatistical Methods and Applications in Clinical Oncology. Singapore: Springer; 2017. p. 413\u201334.","DOI":"10.1007\/978-981-10-0126-0_25"},{"issue":"6","key":"2638_CR4","doi-asserted-by":"publisher","first-page":"e40262","DOI":"10.1371\/journal.pone.0040262","volume":"7","author":"J-J Lu","year":"2012","unstructured":"Lu J-J, Pan W, Hu Y-J, Wang Y-T. Multi-target drugs: the trend of drug research and development. PLoS One. 2012;7(6):e40262.","journal-title":"PLoS One"},{"key":"2638_CR5","doi-asserted-by":"crossref","unstructured":"Widakowich C, de Castro G, De Azambuja E, Dinh P, Awada A: Side effects of approved molecular targeted therapies in solid cancers. The oncologist. 2007;12(12):1443\u201355.","DOI":"10.1634\/theoncologist.12-12-1443"},{"issue":"7","key":"2638_CR6","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/nmeth.3440","volume":"12","author":"P Creixell","year":"2015","unstructured":"Creixell P, Reimand J, Haider S, Wu G, Shibata T, Vazquez M, Mustonen V, Gonzalez-Perez A, Pearson J, Sander C. Pathway and network analysis of cancer genomes. Nat Methods. 2015;12(7):615.","journal-title":"Nat Methods"},{"issue":"1","key":"2638_CR7","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.","journal-title":"Nat Rev Genet"},{"issue":"6","key":"2638_CR8","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1039\/c3mb25382a","volume":"9","author":"Z Wu","year":"2013","unstructured":"Wu Z, Wang Y, Chen L. Network-based drug repositioning. Mol BioSyst. 2013;9(6):1268\u201381.","journal-title":"Mol BioSyst"},{"key":"2638_CR9","volume-title":"An introduction to metabolic pathways","author":"S Dagley","year":"1970","unstructured":"Dagley S, Nicholson D. An introduction to metabolic pathways. Oxford: Blackwell Scientific Publications; 1970. xi"},{"issue":"5","key":"2638_CR10","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1093\/bioinformatics\/btq714","volume":"27","author":"X Chen","year":"2010","unstructured":"Chen X, Xu J, Huang B, Li J, Wu X, Ma L, Jia X, Bian X, Tan F, Liu L. A sub-pathway-based approach for identifying drug response principal network. Bioinformatics. 2010;27(5):649\u201354.","journal-title":"Bioinformatics"},{"issue":"1","key":"2638_CR11","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/1752-0509-7-139","volume":"7","author":"F Iorio","year":"2013","unstructured":"Iorio F, Saez-Rodriguez J, Di Bernardo D. Network based elucidation of drug response: from modulators to targets. BMC Syst Biol. 2013;7(1):139.","journal-title":"BMC Syst Biol"},{"issue":"189","key":"2638_CR12","doi-asserted-by":"publisher","first-page":"rs8","DOI":"10.1126\/scisignal.2001699","volume":"4","author":"A Vinayagam","year":"2011","unstructured":"Vinayagam A, Stelzl U, Foulle R, Plassmann S, Zenkner M, Timm J, Assmus HE, Andrade-Navarro MA, Wanker EE. A directed protein interaction network for investigating intracellular signal transduction. Sci Signal. 2011;4(189):rs8.","journal-title":"Sci Signal"},{"key":"2638_CR13","doi-asserted-by":"crossref","unstructured":"Yu, Hasun, et al. \"Prediction of drugs having opposite effects on disease genes in a directed network.\" BMC systems biology. BioMed Central, 2016;10(1).","DOI":"10.1186\/s12918-015-0243-2"},{"key":"2638_CR14","doi-asserted-by":"crossref","unstructured":"Sharan, Roded, Igor Ulitsky, and Ron Shamir. \"Network\u2010based prediction of protein function.\" Molecular systems biology 3.1. 2007;88.","DOI":"10.1038\/msb4100129"},{"issue":"8","key":"2638_CR15","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1093\/bioinformatics\/btq082","volume":"26","author":"E Corel","year":"2010","unstructured":"Corel E, Pitschi F, Morgenstern B. A min-cut algorithm for the consistency problem in multiple sequence alignment. Bioinformatics. 2010;26(8):1015\u201321.","journal-title":"Bioinformatics"},{"issue":"4","key":"2638_CR16","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/j.neuroimage.2008.07.058","volume":"43","author":"F Lijn van der","year":"2008","unstructured":"van der Lijn F, den Heijer T, Breteler MM, Niessen WJ. Hippocampus segmentation in MR images using atlas registration, voxel classification, and graph cuts. Neuroimage. 2008;43(4):708\u201320.","journal-title":"Neuroimage"},{"issue":"4","key":"2638_CR17","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.tips.2005.02.007","volume":"26","author":"P Csermely","year":"2005","unstructured":"Csermely P, Agoston V, Pongor S. The efficiency of multi-target drugs: the network approach might help drug design. Trends Pharmacol Sci. 2005;26(4):178\u201382.","journal-title":"Trends Pharmacol Sci"},{"issue":"22","key":"2638_CR18","doi-asserted-by":"publisher","first-page":"5866","DOI":"10.1093\/hmg\/ddu309","volume":"23","author":"I Ezkurdia","year":"2014","unstructured":"Ezkurdia I, Juan D, Rodriguez JM, Frankish A, Diekhans M, Harrow J, Vazquez J, Valencia A, Tress ML. Multiple evidence strands suggest that there may be as few as 19 000 human protein-coding genes. Hum Mol Genet. 2014;23(22):5866\u201378.","journal-title":"Hum Mol Genet"},{"key":"2638_CR19","doi-asserted-by":"crossref","unstructured":"Brunham LR, Hayden MR: Hunting human disease genes: lessons from the past, challenges for the future. Human genetics. 2013;132(6):603\u2013617.","DOI":"10.1007\/s00439-013-1286-3"},{"key":"2638_CR20","doi-asserted-by":"crossref","unstructured":"Abdolmaleki A, Ghasemi JB, Ghasemi F. Computer aided drug Design for Multi-Target Drug Design: SAR\/QSAR, molecular docking and pharmacophore methods. Curr Drug Targets. 2017;18(5):556\u201375.","DOI":"10.2174\/1389450117666160101120822"},{"issue":"6","key":"2638_CR21","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1080\/1354750X.2017.1306752","volume":"22","author":"RC Eldridge","year":"2017","unstructured":"Eldridge RC, Flanders WD, Bostick RM, Fedirko V, Gross M, Thyagarajan B, Goodman M. Using multiple biomarkers and determinants to obtain a better measurement of oxidative stress: a latent variable structural equation model approach. Biomarkers. 2017;22(6):517\u201324.","journal-title":"Biomarkers"},{"issue":"5","key":"2638_CR22","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1111\/ane.12761","volume":"136","author":"V Martinelli","year":"2017","unstructured":"Martinelli V, Dalla Costa G, Messina M, Di Maggio G, Sangalli F, Moiola L, Rodegher M, Colombo B, Furlan R, Leocani L. Multiple biomarkers improve the prediction of multiple sclerosis in clinically isolated syndromes. Acta Neurol Scand. 2017;136(5):454\u201361.","journal-title":"Acta Neurol Scand"},{"issue":"6","key":"2638_CR23","doi-asserted-by":"publisher","first-page":"e88","DOI":"10.1371\/journal.pgen.0020088","volume":"2","author":"X He","year":"2006","unstructured":"He X, Zhang J. Why do hubs tend to be essential in protein networks? PLoS Genet. 2006;2(6):e88.","journal-title":"PLoS Genet"},{"issue":"6833","key":"2638_CR24","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/35075138","volume":"411","author":"H Jeong","year":"2001","unstructured":"Jeong H, Mason SP, Barab\u00e1si A-L, Oltvai ZN. Lethality and centrality in protein networks. Nature. 2001;411(6833):41.","journal-title":"Nature"},{"issue":"1","key":"2638_CR25","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/nar\/27.1.29","volume":"27","author":"H Ogata","year":"1999","unstructured":"Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, Kanehisa M. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 1999;27(1):29\u201334.","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"2638_CR26","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/ng0892-345","volume":"1","author":"M Mullan","year":"1992","unstructured":"Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad B, Lannfelt L. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N\u2013terminus of \u03b2\u2013amyloid. Nat Genet. 1992;1(5):345.","journal-title":"Nat Genet"},{"issue":"2","key":"2638_CR27","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1042\/BJ20071619","volume":"412","author":"S Imarisio","year":"2008","unstructured":"Imarisio S, Carmichael J, Korolchuk V, Chen C-W, Saiki S, Rose C, Krishna G, Davies JE, Ttofi E, Underwood BR. Huntington's disease: from pathology and genetics to potential therapies. Biochem J. 2008;412(2):191\u2013209.","journal-title":"Biochem J"},{"issue":"2","key":"2638_CR28","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","volume":"6","author":"AG Porter","year":"1999","unstructured":"Porter AG, J\u00e4nicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6(2):99.","journal-title":"Cell Death Differ"},{"issue":"1","key":"2638_CR29","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1159\/000134061","volume":"71","author":"Y Shibasaki","year":"1995","unstructured":"Shibasaki Y, Baillie D, Clair DS, Brookes A. High-resolution mapping of SNCA encoding \u03b1-synuclein, the non-A\u03b2 component of Alzheimer\u2019s disease amyloid precursor, to human chromosome 4q21. 3\u2192 q22 by fluorescence in situ hybridization. Cytogenet Genome Res. 1995;71(1):54\u20135.","journal-title":"Cytogenet Genome Res"},{"issue":"6","key":"2638_CR30","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1002\/jcla.21986","volume":"30","author":"Q Wang","year":"2016","unstructured":"Wang Q, Tian Q, Song X, Liu Y, Li W. SNCA gene polymorphism may contribute to an increased risk of Alzheimer's disease. J Clin Lab Anal. 2016;30(6):1092\u20139.","journal-title":"J Clin Lab Anal"},{"issue":"9","key":"2638_CR31","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.molmed.2004.07.001","volume":"10","author":"JC Cruz","year":"2004","unstructured":"Cruz JC, Tsai L-H. Cdk5 deregulation in the pathogenesis of Alzheimer\u2019s disease. Trends Mol Med. 2004;10(9):452\u20138.","journal-title":"Trends Mol Med"},{"issue":"1","key":"2638_CR32","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1074\/jbc.M002466200","volume":"276","author":"S Leclerc","year":"2001","unstructured":"Leclerc S, Garnier M, Hoessel R, Marko D, Bibb JA, Snyder GL, Greengard P, Biernat J, Wu Y-Z, Mandelkow E-M. Indirubins inhibit glycogen synthase kinase-3\u03b2 and CDK5\/P25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A property common to most cyclin-dependent kinase inhibitors? J Biol Chem. 2001;276(1):251\u201360.","journal-title":"J Biol Chem"},{"issue":"1\u20132","key":"2638_CR33","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.bbapap.2003.11.019","volume":"1697","author":"L-H Tsai","year":"2004","unstructured":"Tsai L-H, Lee M-S, Cruz J. Cdk5, a therapeutic target for Alzheimer's disease? Biochim Biophys Acta. 2004;1697(1\u20132):137\u201342.","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"2638_CR34","doi-asserted-by":"publisher","first-page":"1602. e1603","DOI":"10.1016\/j.neurobiolaging.2014.11.009","volume":"36","author":"H-Y Jiang","year":"2015","unstructured":"Jiang H-Y, Li G-D, Dai S-X, Bi R, Zhang D-F, Li Z-F, Xu X-F, Zhou T-C, Yu L, Yao Y-G. Identification of PSEN1 mutations p. M233L and p. R352C in Han Chinese families with early-onset familial Alzheimer\u2019s disease. Neurobiol Aging. 2015;36(3):1602. e1603\u20136.","journal-title":"Neurobiol Aging"},{"issue":"8","key":"2638_CR35","doi-asserted-by":"publisher","first-page":"1850. e1817","DOI":"10.1016\/j.neurobiolaging.2012.02.020","volume":"33","author":"E Lohmann","year":"2012","unstructured":"Lohmann E, Guerreiro RJ, Erginel-Unaltuna N, Gurunlian N, Bilgic B, Gurvit H, Hanagasi HA, Luu N, Emre M, Singleton A. Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients. Neurobiol Aging. 2012;33(8):1850. e1817\u201327.","journal-title":"Neurobiol Aging"},{"key":"2638_CR36","doi-asserted-by":"publisher","first-page":"212. e211","DOI":"10.1016\/j.neurobiolaging.2017.04.012","volume":"56","author":"J Park","year":"2017","unstructured":"Park J, An SSA, Van Giau V, Shim K, Youn YC, Bagyinszky E, Kim S. Identification of a novel PSEN1 mutation (Leu232Pro) in a Korean patient with early-onset Alzheimer's disease and a family history of dementia. Neurobiol Aging. 2017;56:212. e211\u20137.","journal-title":"Neurobiol Aging"},{"issue":"3","key":"2638_CR37","doi-asserted-by":"publisher","first-page":"399","DOI":"10.4153\/CJM-1956-045-5","volume":"8","author":"LR Ford","year":"1956","unstructured":"Ford LR, Fulkerson DR. Maximal flow through a network. Can J Math. 1956;8(3):399\u2013404.","journal-title":"Can J Math"},{"issue":"4","key":"2638_CR38","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1145\/263867.263872","volume":"44","author":"M Stoer","year":"1997","unstructured":"Stoer M, Wagner F. A simple min-cut algorithm. JACM. 1997;44(4):585\u201391.","journal-title":"JACM"},{"issue":"23","key":"2638_CR39","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1093\/bioinformatics\/btm369","volume":"23","author":"A Subramanian","year":"2007","unstructured":"Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov JP. GSEA-P: a desktop application for gene set enrichment analysis. Bioinformatics. 2007;23(23):3251\u20133.","journal-title":"Bioinformatics"},{"issue":"43","key":"2638_CR40","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","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. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci. 2005;102(43):15545\u201350.","journal-title":"Proc Natl Acad Sci"},{"issue":"70","key":"2638_CR41","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23061","volume":"8","author":"Y Pan","year":"2017","unstructured":"Pan Y, Liu G, Yuan Y, Zhao J, Yang Y, Li Y. Analysis of differential gene expression profile identifies novel biomarkers for breast cancer. Oncotarget. 2017;8(70):114613.","journal-title":"Oncotarget"},{"issue":"23","key":"2638_CR42","first-page":"6617","volume":"60","author":"S-L Sallinen","year":"2000","unstructured":"Sallinen S-L, Sallinen PK, Haapasalo HK, Helin HJ, Hel\u00e9n PT, Schraml P, Kallioniemi O-P, Kononen J. Identification of differentially expressed genes in human gliomas by DNA microarray and tissue chip techniques. Cancer Res. 2000;60(23):6617\u201322.","journal-title":"Cancer Res"},{"key":"2638_CR43","doi-asserted-by":"crossref","unstructured":"Zhao, Xing-Ming, and Guimin Qin. \"Identifying biomarkers with differential analysis.\" Bioinformatics for Diagnosis, Prognosis and Treatment of Complex Diseases. Dordrecht: Springer; 2013;17\u201331.","DOI":"10.1007\/978-94-007-7975-4_2"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-019-2638-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12859-019-2638-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-019-2638-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T19:04:54Z","timestamp":1581534294000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-019-2638-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,13]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["2638"],"URL":"https:\/\/doi.org\/10.1186\/s12859-019-2638-3","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,13]]},"assertion":[{"value":"9 July 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 January 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2019","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"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"74"}}