{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T01:08:06Z","timestamp":1785287286090,"version":"3.55.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":41,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["T2341024"],"award-info":[{"award-number":["T2341024"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LZ22C060001"],"award-info":[{"award-number":["LZ22C060001"]}]},{"DOI":"10.13039\/501100011332","name":"UCAS","doi-asserted-by":"publisher","award":["2022ZZ01013"],"award-info":[{"award-number":["2022ZZ01013"]}],"id":[{"id":"10.13039\/501100011332","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011332","name":"UCAS","doi-asserted-by":"publisher","award":["2022ZZ01016"],"award-info":[{"award-number":["2022ZZ01016"]}],"id":[{"id":"10.13039\/501100011332","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1004800"],"award-info":[{"award-number":["2022YFA1004800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The progression of complex diseases often involves abrupt and non-linear changes characterized by sudden shifts that trigger critical transformations. Identifying these critical states or tipping points is crucial for understanding disease progression and developing effective interventions. To address this challenge, we have developed a model-free method named Network Information Entropy of Edges (NIEE). Leveraging dynamic network biomarkers, sample-specific networks, and information entropy theories, NIEE can detect critical states or tipping points in diverse data types, including bulk, single-sample expression data. By applying NIEE to real disease datasets, we successfully identified critical predisease stages and tipping points before disease onset. Our findings underscore NIEE\u2019s potential to enhance comprehension of complex disease development.<\/jats:p>","DOI":"10.1093\/bib\/bbae311","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:03:42Z","timestamp":1720051422000},"source":"Crossref","is-referenced-by-count":13,"title":["Detecting tipping points of complex diseases by network information entropy"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0971-2851","authenticated-orcid":false,"given":"Chengshang","family":"Lyu","sequence":"first","affiliation":[{"name":"Key Laboratory of Systems Health Science of Zhejiang Province , School of Life Science, Hangzhou Institute for Advanced Study, , 1 Xiangshan Branch Alley, Xihu District, Hangzhou 310024, China"},{"name":"University of Chinese Academy of Sciences , School of Life Science, Hangzhou Institute for Advanced Study, , 1 Xiangshan Branch Alley, Xihu District, Hangzhou 310024, China"},{"name":"Department of Biomedical Sciences, City University of Hong Kong, 31 To Yuen Street, Kowloon Tong, Kowloon , Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5229-7470","authenticated-orcid":false,"given":"Lingxi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, City University of Hong Kong, 31 To Yuen Street, Kowloon Tong, Kowloon , Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3246-4227","authenticated-orcid":false,"given":"Xiaoping","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systems Health Science of Zhejiang Province , School of Life Science, Hangzhou Institute for Advanced Study, , 1 Xiangshan Branch Alley, Xihu District, Hangzhou 310024, China"},{"name":"University of Chinese Academy of Sciences , School of Life Science, Hangzhou Institute for Advanced Study, , 1 Xiangshan Branch Alley, Xihu District, Hangzhou 310024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"key":"2024070400031307400_ref1","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/srep00342","article-title":"Detecting early-warning signals for sudden deterioration of complex diseases by dynamical network biomarkers","volume":"2","author":"Chen","year":"2012","journal-title":"Sci Rep"},{"key":"2024070400031307400_ref2","doi-asserted-by":"crossref","first-page":"145997","DOI":"10.1016\/j.gene.2021.145997","article-title":"Dynamical network biomarkers: theory and applications","volume":"808","author":"Aihara","year":"2022","journal-title":"Gene"},{"key":"2024070400031307400_ref3","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1186\/1755-8794-6-S2-S8","article-title":"Detecting early-warning signals of type 1 diabetes and its leading biomolecular networks by dynamical network biomarkers","volume":"6","author":"Liu","year":"2013","journal-title":"BMC Med Genomics"},{"key":"2024070400031307400_ref4","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12859-017-1462-x","article-title":"Comparative network stratification analysis for identifying functional interpretable network biomarkers","volume":"18","author":"Zhang","year":"2017","journal-title":"BMC Bioinformatics"},{"key":"2024070400031307400_ref5","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41467-018-03024-2","article-title":"Dynamic network biomarker indicates pulmonary metastasis at the tipping point of hepatocellular carcinoma","volume":"9","author":"Yang","year":"2018","journal-title":"Nat Commun"},{"key":"2024070400031307400_ref6","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/bib\/bbz089","article-title":"Network control principles for identifying personalized driver genes in cancer","volume":"21","author":"Guo","year":"2020","journal-title":"Brief Bioinform"},{"key":"2024070400031307400_ref7","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":"2024070400031307400_ref8","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/s41598-018-19674-7","article-title":"Impaired functional criticality of human brain during Alzheimer's disease progression","volume":"8","author":"Jiang","year":"2018","journal-title":"Sci Rep"},{"key":"2024070400031307400_ref9","first-page":"159","article-title":"Reconstructing dynamic gene regulatory network for the development process of hepatocellular carcinoma","author":"Zhu","year":"2012"},{"key":"2024070400031307400_ref10","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1038\/srep02268","article-title":"Spatio-temporal analysis of type 2 diabetes mellitus based on differential expression networks","volume":"3","author":"Sun","year":"2013","journal-title":"Sci Rep"},{"key":"2024070400031307400_ref11","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/srep00813","article-title":"Identifying critical transitions and their leading biomolecular networks in complex diseases","volume":"2","author":"Liu","year":"2012","journal-title":"Sci Rep"},{"key":"2024070400031307400_ref12","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1093\/bioinformatics\/btu084","article-title":"Identifying critical transitions of complex diseases based on a single sample","volume":"30","author":"Liu","year":"2014","journal-title":"Bioinformatics"},{"key":"2024070400031307400_ref13","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkw772","article-title":"Personalized characterization of diseases using sample-specific networks","volume":"44","author":"Liu","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2024070400031307400_ref14","doi-asserted-by":"crossref","first-page":"10324","DOI":"10.1073\/pnas.1005283107","article-title":"Information-theoretic analysis of phenotype changes in early stages of carcinogenesis","volume":"107","author":"Remacle","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024070400031307400_ref15","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1093\/bioinformatics\/btaa894","article-title":"A novel estimator of the interaction matrix in graphical Gaussian model of omics data using the entropy of non-equilibrium systems","volume":"37","author":"Borzou","year":"2021","journal-title":"Bioinformatics"},{"key":"2024070400031307400_ref16","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1093\/bioinformatics\/btr077","article-title":"Topological entropy of DNA sequences","volume":"27","author":"Koslicki","year":"2011","journal-title":"Bioinformatics"},{"key":"2024070400031307400_ref17","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1093\/bioinformatics\/bty691","article-title":"On entropy and information in gene interaction networks","volume":"35","author":"Wallace","year":"2019","journal-title":"Bioinformatics"},{"key":"2024070400031307400_ref18","doi-asserted-by":"crossref","first-page":"e1002234","DOI":"10.1371\/journal.pgen.1002234","article-title":"Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection","volume":"7","author":"Huang","year":"2011","journal-title":"PLoS Genet"},{"key":"2024070400031307400_ref19","doi-asserted-by":"crossref","first-page":"e52198","DOI":"10.1371\/journal.pone.0052198","article-title":"A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2","volume":"8","author":"Woods","year":"2013","journal-title":"PloS One"},{"key":"2024070400031307400_ref20","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12859-016-0889-9","article-title":"An individualized predictor of health and disease using paired reference and target samples","volume":"17","author":"Liu","year":"2016","journal-title":"BMC Bioinformatics"},{"key":"2024070400031307400_ref21","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1021\/tx050126f","article-title":"Genomic analysis of murine pulmonary tissue following carbonyl chloride inhalation","volume":"18","author":"Sciuto","year":"2005","journal-title":"Chem Res Toxicol"},{"key":"2024070400031307400_ref22","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1056\/NEJMp1607591","article-title":"Toward a shared vision for cancer genomic data","volume":"375","author":"Grossman","year":"2016","journal-title":"N Engl J Med"},{"key":"2024070400031307400_ref23","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.clim.2008.07.028","article-title":"Tissue- and age-specific changes in gene expression during disease induction and progression in NOD mice","volume":"129","author":"Kodama","year":"2008","journal-title":"Clin Immunol"},{"key":"2024070400031307400_ref24","doi-asserted-by":"crossref","first-page":"e1005633","DOI":"10.1371\/journal.pcbi.1005633","article-title":"Quantifying critical states of complex diseases using single-sample dynamic network biomarkers","volume":"13","author":"Liu","year":"2017","journal-title":"PLoS Comput Biol"},{"key":"2024070400031307400_ref25","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1093\/bioinformatics\/btz758","article-title":"Single-sample landscape entropy reveals the imminent phase transition during disease progression","volume":"36","author":"Liu","year":"2020","journal-title":"Bioinformatics"},{"key":"2024070400031307400_ref26","article-title":"Ten years of pathway analysis: current approaches and outstanding challenges","volume":"8","author":"Ouzounis","year":"2012","journal-title":"PLoS Comput Biol"},{"key":"2024070400031307400_ref27","doi-asserted-by":"crossref","first-page":"D26","DOI":"10.1093\/nar\/gkl993","article-title":"Entrez gene: gene-centered information at NCBI","volume":"35","author":"Maglott","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2024070400031307400_ref28","doi-asserted-by":"crossref","first-page":"D587","DOI":"10.1093\/nar\/gkac963","article-title":"KEGG for taxonomy-based analysis of pathways and genomes","volume":"51","author":"Kanehisa","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2024070400031307400_ref29","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/84219","article-title":"Lymphocyte traffic control by chemokines","volume":"2","author":"Moser","year":"2001","journal-title":"Nat Immunol"},{"key":"2024070400031307400_ref30","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1006\/cimm.1998.1379","article-title":"CCR5 has an expanded ligand-binding repertoire and is the primary receptor used by MCP-2 on activated T cells","volume":"189","author":"Ruffing","year":"1998","journal-title":"Cell Immunol"},{"key":"2024070400031307400_ref31","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12865-017-0237-5","article-title":"Functional expression of CCL8 and its interaction with chemokine receptor CCR3","volume":"18","author":"Ge","year":"2017","journal-title":"BMC Immunol"},{"key":"2024070400031307400_ref32","doi-asserted-by":"crossref","first-page":"e1008334","DOI":"10.1371\/journal.ppat.1008334","article-title":"Two waves of pro-inflammatory factors are released during the influenza a virus (IAV)-driven pulmonary immunopathogenesis","volume":"16","author":"Zhang","year":"2020","journal-title":"PLoS Pathog"},{"key":"2024070400031307400_ref33","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.virol.2010.02.020","article-title":"Modeling host responses in ferrets during a\/California\/07\/2009 influenza infection","volume":"401","author":"Rowe","year":"2010","journal-title":"Virology"},{"key":"2024070400031307400_ref34","article-title":"Synergistic up-regulation of CXCL10 by virus and IFN \u03b3 in human airway epithelial cells","volume":"9","author":"Di","year":"2014","journal-title":"PloS One"},{"key":"2024070400031307400_ref35","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1126\/science.273.5280.1392","article-title":"Crystal structure of the Aequorea victoria green fluorescent protein","volume":"273","author":"Ormo","year":"1996","journal-title":"Science"},{"key":"2024070400031307400_ref36","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nprot.2016.169","article-title":"The ClusPro web server for protein-protein docking","volume":"12","author":"Kozakov","year":"2017","journal-title":"Nat Protoc"},{"key":"2024070400031307400_ref37","doi-asserted-by":"crossref","first-page":"e80976","DOI":"10.1371\/journal.pone.0080976","article-title":"Ubiquitin-specific proteases 25 negatively regulates virus-induced type I interferon signaling","volume":"8","author":"Zhong","year":"2013","journal-title":"PloS One"},{"key":"2024070400031307400_ref38","doi-asserted-by":"crossref","first-page":"7500","DOI":"10.1073\/pnas.0611551104","article-title":"Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125","volume":"104","author":"Arimoto","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024070400031307400_ref39","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.chom.2009.07.006","article-title":"Gene expression signatures diagnose influenza and other symptomatic respiratory viral infections in humans","volume":"6","author":"Zaas","year":"2009","journal-title":"Cell Host Microbe"},{"key":"2024070400031307400_ref40","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nrc.2016.25","article-title":"Targeting metastasis","volume":"16","author":"Steeg","year":"2016","journal-title":"Nat Rev Cancer"},{"key":"2024070400031307400_ref41","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4757-3656-4","volume-title":"AJCC Cancer Staging Manual","author":"Greene","year":"2002"},{"key":"2024070400031307400_ref42","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ymeth.2014.11.020","article-title":"DISEASES: text mining and data integration of disease-gene associations","volume":"74","author":"Pletscher-Frankild","year":"2015","journal-title":"Methods"},{"key":"2024070400031307400_ref43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/676731","article-title":"Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins","volume":"2012","author":"Bendas","year":"2012","journal-title":"Int J Cell Biol"},{"key":"2024070400031307400_ref44","doi-asserted-by":"crossref","first-page":"100040","DOI":"10.1016\/j.clinsp.2022.100040","article-title":"L1 cell adhesion molecule high expression is associated with poor prognosis in surgically resected brain metastases from lung adenocarcinoma","volume":"77","author":"Wang","year":"2022","journal-title":"Clinics (Sao Paulo)"},{"key":"2024070400031307400_ref45","doi-asserted-by":"crossref","first-page":"e91","DOI":"10.1093\/nar\/gkac452","article-title":"Detecting critical transition signals from single-cell transcriptomes to infer lineage-determining transcription factors","volume":"50","author":"Yang","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2024070400031307400_ref46","doi-asserted-by":"crossref","DOI":"10.1093\/bioadv\/vbae099","article-title":"Current and future directions in network biology","author":"Zitnik","year":"2024"},{"key":"2024070400031307400_ref47","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.gpb.2020.05.005","article-title":"c-CSN: single-cell RNA sequencing data analysis by conditional cell-specific network","volume":"19","author":"Li","year":"2021","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"2024070400031307400_ref48","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1093\/bib\/bbaa062","article-title":"Disease characterization using a partial correlation-based sample-specific network","volume":"22","author":"Huang","year":"2021","journal-title":"Brief Bioinform"},{"key":"2024070400031307400_ref49","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1093\/nar\/gkz172","article-title":"Cell-specific network constructed by single-cell RNA sequencing data","volume":"47","author":"Dai","year":"2019","journal-title":"Nucleic Acids Res"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/4\/bbae311\/58425649\/bbae311.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/4\/bbae311\/58425649\/bbae311.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T21:59:35Z","timestamp":1732226375000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbae311\/7705534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,23]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,5,23]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbae311","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7]]},"published":{"date-parts":[[2024,5,23]]},"article-number":"bbae311"}}