{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T20:39:18Z","timestamp":1778704758162,"version":"3.51.4"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Alzheimer\u2019s disease (AD) is a severe neurodegenerative disease of the central nervous system that may be caused by perturbation of regulatory pathways rather than the dysfunction of a single gene. However, the pathology of AD has yet to be fully elucidated.<\/jats:p><jats:p>Results: In this study, we systematically analyzed AD-related mRNA and miRNA expression profiles as well as curated transcription factor (TF) and miRNA regulation to identify active TF and miRNA regulatory pathways in AD. By mapping differentially expressed genes and miRNAs to the curated TF and miRNA regulatory network as active seed nodes, we obtained a potential active subnetwork in AD. Next, by using the breadth-first-search technique, potential active regulatory pathways, which are the regulatory cascade of TFs, miRNAs and their target genes, were identified. Finally, based on the known AD-related genes and miRNAs, the hypergeometric test was used to identify active pathways in AD. As a result, nine pathways were found to be significantly activated in AD. A comprehensive literature review revealed that eight out of nine genes and miRNAs in these active pathways were associated with AD. In addition, we inferred that the pathway hsa-miR-146a\u2192STAT1\u2192MYC, which is the source of all nine significantly active pathways, may play an important role in AD progression, which should be further validated by biological experiments. Thus, this study provides an effective approach to finding active TF and miRNA regulatory pathways in AD and can be easily applied to other complex diseases.<\/jats:p><jats:p>Contact: \u00a0lixia@hrbmu.edu.cn or lw2247@gmail.com.<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btt423","type":"journal-article","created":{"date-parts":[[2013,8,30]],"date-time":"2013-08-30T00:39:04Z","timestamp":1377823144000},"page":"2596-2602","source":"Crossref","is-referenced-by-count":57,"title":["Identification of active transcription factor and miRNA regulatory pathways in Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"29","author":[{"given":"Wei","family":"Jiang","sequence":"first","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanlin","family":"Meng","sequence":"additional","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baofeng","family":"Lian","sequence":"additional","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Chen","sequence":"additional","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuexin","family":"Yu","sequence":"additional","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enyu","family":"Dai","sequence":"additional","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"Liu","sequence":"additional","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihong","family":"Wang","sequence":"additional","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"1 College of Bioinformatics Science and Technology, 2Department of Internal Neurology, Fourth Affiliated Hospital and 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,8,29]]},"reference":[{"key":"2023012810464850500_btt423-B1","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1093\/nar\/gkr1227","article-title":"An integer linear programming approach for finding deregulated subgraphs in regulatory networks","volume":"40","author":"Backes","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023012810464850500_btt423-B2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"2023012810464850500_btt423-B3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: target recognition and regulatory functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell"},{"key":"2023012810464850500_btt423-B4","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1093\/brain\/awh193","article-title":"Association of protein kinase C alpha (PRKCA) gene with multiple sclerosis in a UK population","volume":"127","author":"Barton","year":"2004","journal-title":"Brain"},{"key":"2023012810464850500_btt423-B5","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0169-328X(99)00119-9","article-title":"The Alzheimer-related gene presenilin 1 facilitates notch 1 in primary mammalian neurons","volume":"69","author":"Berezovska","year":"1999","journal-title":"Brain Res. Mol. Brain Res."},{"key":"2023012810464850500_btt423-B6","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/j.1471-4159.2006.03705.x","article-title":"Visualization of APP dimerization and APP-Notch2 heterodimerization in living cells using bimolecular fluorescence complementation","volume":"97","author":"Chen","year":"2006","journal-title":"J. Neurochem."},{"key":"2023012810464850500_btt423-B7","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1186\/1471-2105-12-S1-S41","article-title":"Coregulation of transcription factors and microRNAs in human transcriptional regulatory network","volume":"12","author":"Chen","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2023012810464850500_btt423-B8","first-page":"1259","article-title":"Involvement of CDK4, pRB, and E2F1 in ginsenoside Rg1 protecting rat cortical neurons from beta-amyloid-induced apoptosis","volume":"24","author":"Chen","year":"2003","journal-title":"Acta Pharmacol. Sin."},{"key":"2023012810464850500_btt423-B9","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1752-0509-5-117","article-title":"An integrative approach to inferring biologically meaningful gene modules","volume":"5","author":"Cho","year":"2011","journal-title":"BMC Syst. Biol."},{"key":"2023012810464850500_btt423-B10","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1128\/MCB.24.2.865-874.2004","article-title":"Transcriptional regulation of BACE1, the beta-amyloid precursor protein beta-secretase, by Sp1","volume":"24","author":"Christensen","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"2023012810464850500_btt423-B11","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1002\/jnr.21695","article-title":"Transcription factor Sp1 dysregulation in Alzheimer's disease","volume":"86","author":"Citron","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"2023012810464850500_btt423-B12","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene expression omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2023012810464850500_btt423-B13","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/S0169-328X(00)00062-0","article-title":"N-myc and c-myc expression in Alzheimer disease, Huntington disease and Parkinson disease","volume":"77","author":"Ferrer","year":"2000","journal-title":"Brain Res. Mol. Brain Res."},{"key":"2023012810464850500_btt423-B14","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1186\/1471-2105-14-S2-S7","article-title":"Discovery and analysis of consistent active sub-networks in cancers","volume":"14","author":"Gaire","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2023012810464850500_btt423-B15","doi-asserted-by":"crossref","first-page":"6415","DOI":"10.1073\/pnas.0710263105","article-title":"Loss of microRNA cluster miR-29a\/b-1 in sporadic Alzheimer's disease correlates with increased BACE1\/beta-secretase expression","volume":"105","author":"Hebert","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012810464850500_btt423-B16","first-page":"320","article-title":"Clinical inquiries. Do patients at high risk of Alzheimer's disease benefit from early treatment?","volume":"58","author":"Holt","year":"2009","journal-title":"J. Fam. Pract."},{"key":"2023012810464850500_btt423-B17","doi-asserted-by":"crossref","first-page":"D163","DOI":"10.1093\/nar\/gkq1107","article-title":"miRTarBase: a database curates experimentally validated microRNA-target interactions","volume":"39","author":"Hsu","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2023012810464850500_btt423-B18","doi-asserted-by":"crossref","first-page":"S233","DOI":"10.1093\/bioinformatics\/18.suppl_1.S233","article-title":"Discovering regulatory and signalling circuits in molecular interaction networks","volume":"18","author":"Ideker","year":"2002","journal-title":"Bioinformatics"},{"key":"2023012810464850500_btt423-B19","doi-asserted-by":"crossref","first-page":"13042","DOI":"10.1073\/pnas.2135111100","article-title":"Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis","volume":"100","author":"Ikonen","year":"2003","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012810464850500_btt423-B20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1017\/S0016672307008646","article-title":"A structural mixed model for variances in differential gene expression studies","volume":"89","author":"Jaffrezic","year":"2007","journal-title":"Genet Res."},{"key":"2023012810464850500_btt423-B21","doi-asserted-by":"crossref","first-page":"D98","DOI":"10.1093\/nar\/gkn714","article-title":"miR2Disease: a manually curated database for microRNA deregulation in human disease","volume":"37","author":"Jiang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012810464850500_btt423-B22","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.pharmthera.2011.10.002","article-title":"MicroRNAs in neurodegenerative diseases and their therapeutic potential","volume":"133","author":"Junn","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"2023012810464850500_btt423-B23","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.2337\/db11-0082","article-title":"Diabetes complications: the microRNA perspective","volume":"60","author":"Kantharidis","year":"2011","journal-title":"Diabetes"},{"key":"2023012810464850500_btt423-B24","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1093\/bioinformatics\/btp510","article-title":"A novel algorithm for detecting differentially regulated paths based on gene set enrichment analysis","volume":"25","author":"Keller","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012810464850500_btt423-B25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0304-3940(97)00797-0","article-title":"Alteration of transcription factors NF-kappaB and STAT1 in Alzheimer's disease brains","volume":"237","author":"Kitamura","year":"1997","journal-title":"Neurosci. Lett."},{"key":"2023012810464850500_btt423-B26","first-page":"189","article-title":"Molecular expression profiling with respect to KEGG hsa05219 pathway","volume":"5","author":"Krishnappa","year":"2011","journal-title":"Ecancermedicalscience"},{"key":"2023012810464850500_btt423-B27","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.neurobiolaging.2003.12.024","article-title":"Apolipoprotein gene and its interaction with the environmentally driven risk factors: molecular, genetic and epidemiological studies of Alzheimer's disease","volume":"25","author":"Lahiri","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"2023012810464850500_btt423-B28","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0304-3940(03)00795-X","article-title":"Myeloperoxidase G-463A polymorphism and Alzheimer's disease in the ApoEurope study","volume":"349","author":"Leininger-Muller","year":"2003","journal-title":"Neurosci. Lett."},{"key":"2023012810464850500_btt423-B29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/bib\/bbr043","article-title":"Dissection of human MiRNA regulatory influence to subpathway","volume":"13","author":"Li","year":"2012","journal-title":"Brief. Bioinform."},{"key":"2023012810464850500_btt423-B30","doi-asserted-by":"crossref","first-page":"e40498","DOI":"10.1371\/journal.pone.0040498","article-title":"Concerted perturbation observed in a hub network in Alzheimer's disease","volume":"7","author":"Liang","year":"2012","journal-title":"PLoS One"},{"key":"2023012810464850500_btt423-B31","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1152\/physiolgenomics.00208.2006","article-title":"Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain","volume":"28","author":"Liang","year":"2007","journal-title":"Physiol. Genomics"},{"key":"2023012810464850500_btt423-B32","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1186\/1752-0509-4-S2-S11","article-title":"Identifying dysfunctional crosstalk of pathways in various regions of Alzheimer's disease brains","volume":"4","author":"Liu","year":"2010","journal-title":"BMC Syst. Biol."},{"key":"2023012810464850500_btt423-B33","doi-asserted-by":"crossref","first-page":"e3420","DOI":"10.1371\/journal.pone.0003420","article-title":"An analysis of human microRNA and disease associations","volume":"3","author":"Lu","year":"2008","journal-title":"PLoS One"},{"key":"2023012810464850500_btt423-B34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12035-012-8234-4","article-title":"Regulation of complement factor H (CFH) by multiple miRNAs in Alzheimer's disease (AD) brain","volume":"46","author":"Lukiw","year":"2012","journal-title":"Mol. Neurobiol."},{"key":"2023012810464850500_btt423-B35","doi-asserted-by":"crossref","first-page":"31315","DOI":"10.1074\/jbc.M805371200","article-title":"An NF-kappaB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells","volume":"283","author":"Lukiw","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2023012810464850500_btt423-B36","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/ni.2073","article-title":"The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-gamma","volume":"12","author":"Ma","year":"2011","journal-title":"Nat. Immunol."},{"key":"2023012810464850500_btt423-B37","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/ajmg.b.30973","article-title":"Functional characterization of three single-nucleotide polymorphisms present in the human APOE promoter sequence: differential effects in neuronal cells and on DNA-protein interactions","volume":"153B","author":"Maloney","year":"2010","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"2023012810464850500_btt423-B38","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1093\/bioinformatics\/btp444","article-title":"Moderated effect size and P-value combinations for microarray meta-analyses","volume":"25","author":"Marot","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012810464850500_btt423-B39","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/435745a","article-title":"Cancer genomics: small RNAs with big impacts","volume":"435","author":"Meltzer","year":"2005","journal-title":"Nature"},{"key":"2023012810464850500_btt423-B40","doi-asserted-by":"crossref","first-page":"e5526","DOI":"10.1371\/journal.pone.0005526","article-title":"Network analysis of differential expression for the identification of disease-causing genes","volume":"4","author":"Nitsch","year":"2009","journal-title":"PLoS One"},{"key":"2023012810464850500_btt423-B41","doi-asserted-by":"crossref","first-page":"e8898","DOI":"10.1371\/journal.pone.0008898","article-title":"Joint genome-wide profiling of miRNA and mRNA expression in Alzheimer's disease cortex reveals altered miRNA regulation","volume":"5","author":"Nunez-Iglesias","year":"2010","journal-title":"PLoS One"},{"key":"2023012810464850500_btt423-B42","first-page":"146","article-title":"An optimized sponge for microRNA miR-9 affects spinal motor neuron development in vivo","volume":"5","author":"Otaegi","year":"2011","journal-title":"Front. Neurosci."},{"key":"2023012810464850500_btt423-B43","doi-asserted-by":"crossref","first-page":"14412","DOI":"10.1074\/jbc.271.24.14412","article-title":"An Alu element in the myeloperoxidase promoter contains a composite SP1-thyroid hormone-retinoic acid response element","volume":"271","author":"Piedrafita","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2023012810464850500_btt423-B44","doi-asserted-by":"crossref","first-page":"e184","DOI":"10.1371\/journal.pmed.0050184","article-title":"Key issues in conducting a meta-analysis of gene expression microarray datasets","volume":"5","author":"Ramasamy","year":"2008","journal-title":"PLoS Med."},{"key":"2023012810464850500_btt423-B45","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/1742-2094-8-34","article-title":"The CCAAT\/enhancer binding protein (C\/EBP) delta is differently regulated by fibrillar and oligomeric forms of the Alzheimer amyloid-beta peptide","volume":"8","author":"Ramberg","year":"2011","journal-title":"J. Neuroinflammation"},{"key":"2023012810464850500_btt423-B46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1752-0509-4-8","article-title":"A general co-expression network-based approach to gene expression analysis: comparison and applications","volume":"4","author":"Ruan","year":"2010","journal-title":"BMC Syst. Biol."},{"key":"2023012810464850500_btt423-B47","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1093\/bioinformatics\/18.11.1542","article-title":"GeneCards 2002: towards a complete, object-oriented, human gene compendium","volume":"18","author":"Safran","year":"2002","journal-title":"Bioinformatics"},{"key":"2023012810464850500_btt423-B48","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neulet.2005.11.062","article-title":"Abnormal Sp1 transcription factor expression in Alzheimer disease and tauopathies","volume":"397","author":"Santpere","year":"2006","journal-title":"Neurosci. Lett."},{"key":"2023012810464850500_btt423-B49","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1261\/rna.2239606","article-title":"TarBase: A comprehensive database of experimentally supported animal microRNA targets","volume":"12","author":"Sethupathy","year":"2006","journal-title":"RNA"},{"key":"2023012810464850500_btt423-B50","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/j.1365-2990.2010.01076.x","article-title":"Aberrant microRNA expression in the brains of neurodegenerative diseases: miR-29a decreased in Alzheimer disease brains targets neurone navigator 3","volume":"36","author":"Shioya","year":"2010","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"2023012810464850500_btt423-B51","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrn785","article-title":"gamma-Secretase, Notch, Abeta and Alzheimer's disease: where do the presenilins fit in?","volume":"3","author":"Sisodia","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"2023012810464850500_btt423-B52","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.cell.2011.09.041","article-title":"An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma","volume":"147","author":"Sumazin","year":"2011","journal-title":"Cell"},{"key":"2023012810464850500_btt423-B53","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jalz.2011.02.004","article-title":"2011 Alzheimer's disease facts and figures","volume":"7","author":"Thies","year":"2011","journal-title":"Alzheimers Dement."},{"key":"2023012810464850500_btt423-B54","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.biocel.2004.07.009","article-title":"The role of inflammation in Alzheimer's disease","volume":"37","author":"Tuppo","year":"2005","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"2023012810464850500_btt423-B55","doi-asserted-by":"crossref","first-page":"i237","DOI":"10.1093\/bioinformatics\/btq182","article-title":"Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM","volume":"26","author":"Vaske","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012810464850500_btt423-B56","doi-asserted-by":"crossref","first-page":"W498","DOI":"10.1093\/nar\/gks494","article-title":"DIANA miRPath v.2.0: investigating the combinatorial effect of microRNAs in pathways","volume":"40","author":"Vlachos","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023012810464850500_btt423-B57","doi-asserted-by":"crossref","first-page":"D119","DOI":"10.1093\/nar\/gkp803","article-title":"TransmiR: a transcription factor-microRNA regulation database","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2023012810464850500_btt423-B58","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1523\/JNEUROSCI.5065-07.2008","article-title":"The expression of microRNA miR-107 decreases early in Alzheimer's disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1","volume":"28","author":"Wang","year":"2008","journal-title":"J. Neurosci."},{"key":"2023012810464850500_btt423-B59","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1093\/nar\/28.1.316","article-title":"TRANSFAC: an integrated system for gene expression regulation","volume":"28","author":"Wingender","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2023012810464850500_btt423-B60","doi-asserted-by":"crossref","first-page":"8208","DOI":"10.1073\/pnas.94.15.8208","article-title":"Interaction between amyloid precursor protein and presenilins in mammalian cells: implications for the pathogenesis of Alzheimer disease","volume":"94","author":"Xia","year":"1997","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012810464850500_btt423-B61","doi-asserted-by":"crossref","first-page":"D105","DOI":"10.1093\/nar\/gkn851","article-title":"miRecords: an integrated resource for microRNA-target interactions","volume":"37","author":"Xiao","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012810464850500_btt423-B62","doi-asserted-by":"crossref","first-page":"e24306","DOI":"10.1371\/journal.pone.0024306","article-title":"Ranking candidate disease genes from gene expression and protein interaction: a Katz-centrality based approach","volume":"6","author":"Zhao","year":"2011","journal-title":"PLoS One"},{"key":"2023012810464850500_btt423-B63","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/nm.2815","article-title":"The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-alpha","volume":"18","author":"Zhu","year":"2012","journal-title":"Nat. Med."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/29\/20\/2596\/48889726\/bioinformatics_29_20_2596.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/29\/20\/2596\/48889726\/bioinformatics_29_20_2596.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T12:52:42Z","timestamp":1715950362000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/29\/20\/2596\/276612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,29]]},"references-count":63,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2013,10,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btt423","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2013,10,15]]},"published":{"date-parts":[[2013,8,29]]}}}