{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:35:00Z","timestamp":1772138100565,"version":"3.50.1"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T00:00:00Z","timestamp":1577145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01HL137159"],"award-info":[{"award-number":["U01HL137159"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01LM012087"],"award-info":[{"award-number":["R01LM012087"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Complex diseases involve perturbation in multiple pathways and a major challenge in clinical genomics is characterizing pathway perturbations in individual samples. This can lead to patient-specific identification of the underlying mechanism of disease thereby improving diagnosis and personalizing treatment. Existing methods rely on external databases to quantify pathway activity scores. This ignores the data dependencies and that pathways are incomplete or condition-specific.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ssNPA is a new approach for subtyping samples based on deregulation of their gene networks. ssNPA learns a causal graph directly from control data. Sample-specific network neighborhood deregulation is quantified via the error incurred in predicting the expression of each gene from its Markov blanket. We evaluate the performance of ssNPA on liver development single-cell RNA-seq data, where the correct cell timing is recovered; and two TCGA datasets, where ssNPA patient clusters have significant survival differences. In all analyses ssNPA consistently outperforms alternative methods, highlighting the advantage of network-based approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>http:\/\/www.benoslab.pitt.edu\/Software\/ssnpa\/.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btz949","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T07:15:12Z","timestamp":1576739712000},"page":"2515-2521","source":"Crossref","is-referenced-by-count":21,"title":["Causal network perturbations for instance-specific analysis of single cell and disease samples"],"prefix":"10.1093","volume":"36","author":[{"given":"Kristina L","family":"Buschur","sequence":"first","affiliation":[{"name":"Department of Computational and Systems Biology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15260, USA"},{"name":"Joint CMU-Pitt PhD Program in Computational Biology , Pittsburgh, PA 15260, USA"}]},{"given":"Maria","family":"Chikina","sequence":"additional","affiliation":[{"name":"Department of Computational and Systems Biology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15260, USA"}]},{"given":"Panayiotis V","family":"Benos","sequence":"additional","affiliation":[{"name":"Department of Computational and Systems Biology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15260, USA"}]}],"member":"286","published-online":{"date-parts":[[2019,12,24]]},"reference":[{"key":"2023013110263081700_btz949-B1","doi-asserted-by":"crossref","first-page":"e8002","DOI":"10.1371\/journal.pone.0008002","article-title":"Silencing of claudin-11 is associated with increased invasiveness of gastric cancer cells","volume":"4","author":"Agarwal","year":"2009","journal-title":"PLoS One"},{"key":"2023013110263081700_btz949-B2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature08460","article-title":"Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1","volume":"462","author":"Barbie","year":"2009","journal-title":"Nature"},{"key":"2023013110263081700_btz949-B3","doi-asserted-by":"crossref","first-page":"13648","DOI":"10.1038\/ncomms13648","article-title":"SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer","volume":"7","author":"Bon","year":"2016","journal-title":"Nat. Commun"},{"key":"2023013110263081700_btz949-B4","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol"},{"key":"2023013110263081700_btz949-B5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive molecular portraits of human breast tumours","volume":"490","year":"2012","journal-title":"Nature"},{"key":"2023013110263081700_btz949-B6","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nature11404","article-title":"Comprehensive genomic characterization of squamous cell lung cancers","volume":"489","year":"2012","journal-title":"Nature"},{"key":"2023013110263081700_btz949-B7","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1038\/s41422-018-0074-y","article-title":"Single-cell RNA-seq uncovers dynamic processes and critical regulators in mouse spermatogenesis","volume":"28","author":"Chen","year":"2018","journal-title":"Cell Res"},{"key":"2023013110263081700_btz949-B8","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1002\/ijc.29565","article-title":"Transcriptional regulation of tenascin-W by TGF-beta signaling in the bone metastatic niche of breast cancer cells","volume":"137","author":"Chiovaro","year":"2015","journal-title":"Int. J. Cancer"},{"key":"2023013110263081700_btz949-B9","doi-asserted-by":"crossref","first-page":"3197","DOI":"10.1172\/JCI60517","article-title":"FAM83B mediates EGFR-and RAS-driven oncogenic transformation","volume":"122","author":"Cipriano","year":"2012","journal-title":"J. Clin. Invest"},{"key":"2023013110263081700_btz949-B10","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1158\/1541-7786.MCR-13-0289","article-title":"Conserved oncogenic behavior of the FAM83 family regulates MAPK signaling in human cancer","volume":"12","author":"Cipriano","year":"2014","journal-title":"Mol. Cancer Res"},{"key":"2023013110263081700_btz949-B11","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aal5209","article-title":"Improving genetic diagnosis in Mendelian disease with transcriptome sequencing","volume":"9","author":"Cummings","year":"2017","journal-title":"Sci. Transl. Med"},{"key":"2023013110263081700_btz949-B12","doi-asserted-by":"crossref","first-page":"6388","DOI":"10.1073\/pnas.1219651110","article-title":"Pathway-based personalized analysis of cancer","volume":"110","author":"Drier","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023013110263081700_btz949-B13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization paths for generalized linear models via coordinate descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J. Stat. Softw"},{"key":"2023013110263081700_btz949-B14","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1126\/science.1094068","article-title":"Inferring cellular networks using probabilistic graphical models","volume":"303","author":"Friedman","year":"2004","journal-title":"Science"},{"key":"2023013110263081700_btz949-B15","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1136\/amiajnl-2013-002519","article-title":"N-of-1-pathways\u2019 unveils personal deregulated mechanisms from a single pair of RNA-Seq samples: towards precision medicine","volume":"21","author":"Gardeux","year":"2014","journal-title":"J. Am. Med. Inf. Assoc"},{"key":"2023013110263081700_btz949-B16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"Hanzelmann","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2023013110263081700_btz949-B17","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1093\/emboj\/19.5.1034","article-title":"Loss of FBP function arrests cellular proliferation and extinguishes c-myc expression","volume":"19","author":"He","year":"2000","journal-title":"EMBO J"},{"key":"2023013110263081700_btz949-B18","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1101\/gad.194101","article-title":"Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development","volume":"15","author":"Hendrich","year":"2001","journal-title":"Genes Dev"},{"key":"2023013110263081700_btz949-B19","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.2353\/ajpath.2006.050596","article-title":"Aquaporin 1 is overexpressed in lung cancer and stimulates NIH-3T3 cell proliferation and anchorage-independent growth","volume":"168","author":"Hoque","year":"2006","journal-title":"Am. J. Pathol"},{"key":"2023013110263081700_btz949-B20","first-page":"431","article-title":"T-ReCS: stable selection of dynamically formed groups of features with application to prediction of clinical outcomes","author":"Huang","year":"2015","journal-title":"Pac. Symp. Biocomput"},{"key":"2023013110263081700_btz949-B21","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.biocel.2012.12.002","article-title":"PRR11 is a novel gene implicated in cell cycle progression and lung cancer","volume":"45","author":"Ji","year":"2013","journal-title":"Int. J. Biochem. Cell Biol"},{"key":"2023013110263081700_btz949-B22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"2023013110263081700_btz949-B23","doi-asserted-by":"crossref","first-page":"27396","DOI":"10.1074\/jbc.M112.359109","article-title":"Contribution of microRNA-1275 to Claudin11 protein suppression via a polycomb-mediated silencing mechanism in human glioma stem-like cells","volume":"287","author":"Katsushima","year":"2012","journal-title":"J. Biol. Chem"},{"key":"2023013110263081700_btz949-B24","doi-asserted-by":"crossref","first-page":"15824","DOI":"10.1038\/ncomms15824","article-title":"Genetic diagnosis of Mendelian disorders via RNA sequencing","volume":"8","author":"Kremer","year":"2017","journal-title":"Nat. Commun"},{"key":"2023013110263081700_btz949-B25","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1517\/14728222.2011.553611","article-title":"Calpains as potential anti-cancer targets","volume":"15","author":"Leloup","year":"2011","journal-title":"Expert Opin. Therap. Targets"},{"key":"2023013110263081700_btz949-B26","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s13046-018-0754-y","article-title":"Inactivation of the tight junction gene CLDN11 by aberrant hypermethylation modulates tubulins polymerization and promotes cell migration in nasopharyngeal carcinoma","volume":"37","author":"Li","year":"2018","journal-title":"J. Exp. Clin. Cancer Res"},{"key":"2023013110263081700_btz949-B27","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12920-017-0263-4","article-title":"N-of-1-pathways MixEnrich: advancing precision medicine via single-subject analysis in discovering dynamic changes of transcriptomes","volume":"10","author":"Li","year":"2017","journal-title":"BMC Med. Genomics"},{"key":"2023013110263081700_btz949-B28","doi-asserted-by":"crossref","first-page":"6067","DOI":"10.18632\/oncotarget.13496","article-title":"MBD3 inhibits formation of liver cancer stem cells","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"2023013110263081700_btz949-B29","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.2147\/OTT.S113855","article-title":"Biomarker discovery to improve prediction of breast cancer survival: using gene expression profiling, meta-analysis, and tissue validation","volume":"9","author":"Meng","year":"2016","journal-title":"Onco Targets Ther"},{"key":"2023013110263081700_btz949-B30","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1038\/s41467-018-03933-2","article-title":"A geometric approach to characterize the functional identity of single cells","volume":"9","author":"Mohammadi","year":"2018","journal-title":"Nat. Commun"},{"key":"2023013110263081700_btz949-B31","doi-asserted-by":"crossref","first-page":"e0117258","DOI":"10.1371\/journal.pone.0117258","article-title":"Calpain-3 impairs cell proliferation and stimulates oxidative stress-mediated cell death in melanoma cells","volume":"10","author":"Moretti","year":"2015","journal-title":"PLoS One"},{"key":"2023013110263081700_btz949-B32","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.biochi.2015.09.010","article-title":"An eccentric calpain, CAPN3\/p94\/calpain-3","volume":"122","author":"Ono","year":"2016","journal-title":"Biochimie"},{"key":"2023013110263081700_btz949-B33","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.bbrc.2017.11.065","article-title":"Biomarker identification for statin sensitivity of cancer cell lines","volume":"495","author":"Raghu","year":"2018","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2023013110263081700_btz949-B34","first-page":"48","author":"Raghu","year":"2018"},{"key":"2023013110263081700_btz949-B35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s41060-018-0104-3","article-title":"Comparison of strategies for scalable causal discovery of latent variable models from mixed data","volume":"6","author":"Raghu","year":"2018","journal-title":"Int. J. Data Sci. Anal"},{"key":"2023013110263081700_btz949-B36","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s41060-016-0032-z","article-title":"A million variables and more: the Fast Greedy Equivalence Search algorithm for learning high-dimensional graphical causal models, with an application to functional magnetic resonance images","volume":"3","author":"Ramsey","year":"2017","journal-title":"Int. J. Data Sci. Anal"},{"key":"2023013110263081700_btz949-B37","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2023013110263081700_btz949-B38","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"2023013110263081700_btz949-B39","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1126\/science.1105809","article-title":"Causal protein-signaling networks derived from multiparameter single-cell data","volume":"308","author":"Sachs","year":"2005","journal-title":"Science"},{"key":"2023013110263081700_btz949-B40","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s12859-016-1039-0","article-title":"Learning mixed graphical models with separate sparsity parameters and stability-based model selection","volume":"17","author":"Sedgewick","year":"2016","journal-title":"BMC Bioinformatics"},{"key":"2023013110263081700_btz949-B41","article-title":"Mixed graphical models for integrative causal analysis with application to chronic lung disease diagnosis and prognosis","volume":"35, 1204\u20131212","author":"Sedgewick","year":"2019","journal-title":"Bioinformatics"},{"key":"2023013110263081700_btz949-B42","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/1878-0261.12016","article-title":"FAM 83 family oncogenes are broadly involved in human cancers: an integrative multi-omics approach","volume":"11","author":"Snijders","year":"2017","journal-title":"Mol. Oncol"},{"key":"2023013110263081700_btz949-B43","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1186\/s12864-017-4342-x","article-title":"Single-cell RNA-Seq analysis reveals dynamic trajectories during mouse liver development","volume":"18","author":"Su","year":"2017","journal-title":"BMC Genomics"},{"key":"2023013110263081700_btz949-B44","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023013110263081700_btz949-B45","doi-asserted-by":"crossref","first-page":"9920","DOI":"10.1073\/pnas.1305172110","article-title":"HMGA2\/TET1\/HOXA9 signaling pathway regulates breast cancer growth and metastasis","volume":"110","author":"Sun","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023013110263081700_btz949-B46","author":"Tenenbaum","year":"2016"},{"key":"2023013110263081700_btz949-B47","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/1471-2105-6-225","article-title":"Pathway level analysis of gene expression using singular value decomposition","volume":"6","author":"Tomfohr","year":"2005","journal-title":"BMC Bioinformatics"},{"key":"2023013110263081700_btz949-B48","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3390\/ijms18020299","article-title":"Role of aquaporin 1 signalling in cancer development and progression","volume":"18","author":"Tomita","year":"2017","journal-title":"Int. J. Mol. Sci"},{"key":"2023013110263081700_btz949-B49","first-page":"2579","article-title":"Visualizing high-dimensional data using t-SNE","volume":"9","author":"van der Maaten","year":"2008","journal-title":"J. Mach. Learn. Res"},{"key":"2023013110263081700_btz949-B50","doi-asserted-by":"crossref","first-page":"eaah4573","DOI":"10.1126\/science.aah4573","article-title":"Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors","volume":"356","author":"Villani","year":"2017","journal-title":"Science"},{"key":"2023013110263081700_btz949-B51","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1140\/epjb\/e2013-40829-0","article-title":"A smart local moving algorithm for large-scale modularity-based community detection","volume":"86","author":"Waltman","year":"2013","journal-title":"Eur. Phys. J. B"},{"key":"2023013110263081700_btz949-B52","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.3892\/or.2015.4107","article-title":"Aquaporin 1 promotes the proliferation and migration of lung cancer cell in vitro","volume":"34","author":"Wei","year":"2015","journal-title":"Oncol. Rep"},{"key":"2023013110263081700_btz949-B53","first-page":"75","article-title":"Aquaporin 1 and aquaporin 4 are involved in invasion of lung cancer cells","volume":"58","author":"Xie","year":"2012","journal-title":"Clin. Lab"},{"key":"2023013110263081700_btz949-B54","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/bjc.2016.397","article-title":"Methyl-CpG-binding domain 3 inhibits epithelial-mesenchymal transition in pancreatic cancer cells via TGF-beta\/Smad signalling","volume":"116","author":"Xu","year":"2017","journal-title":"Br. J. Cancer"},{"key":"2023013110263081700_btz949-B55","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/hep.29353","article-title":"A single-cell transcriptomic analysis reveals precise pathways and regulatory mechanisms underlying hepatoblast differentiation","volume":"66","author":"Yang","year":"2017","journal-title":"Hepatology"},{"key":"2023013110263081700_btz949-B56","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.gendis.2017.12.003","article-title":"Silencing of PRR11 suppresses cell proliferation and induces autophagy in NSCLC cells","volume":"5","author":"Zhang","year":"2018","journal-title":"Genes Dis"},{"key":"2023013110263081700_btz949-B57","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.bbrc.2013.09.121","article-title":"Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha","volume":"440","author":"Zhang","year":"2013","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2023013110263081700_btz949-B58","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.stem.2018.05.025","article-title":"Single-cell RNA-seq reveals dynamic early embryonic-like programs during chemical reprogramming","volume":"23","author":"Zhao","year":"2018","journal-title":"Cell Stem Cell"},{"key":"2023013110263081700_btz949-B59","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12964-019-0422-7","article-title":"Integral membrane protein 2A inhibits cell growth in human breast cancer via enhancing autophagy induction","volume":"17","author":"Zhou","year":"2019","journal-title":"Cell Commun. Signal"},{"key":"2023013110263081700_btz949-B60","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.ajpath.2015.10.028","article-title":"Far upstream element binding protein plays a crucial role in embryonic development, hematopoiesis, and stabilizing Myc expression levels","volume":"186","author":"Zhou","year":"2016","journal-title":"Am. J. Pathol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btz949\/31798878\/btz949.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/36\/8\/2515\/48985845\/bioinformatics_36_8_2515.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/36\/8\/2515\/48985845\/bioinformatics_36_8_2515.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T15:29:49Z","timestamp":1675178989000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/36\/8\/2515\/5686385"}},"subtitle":[],"editor":[{"given":"Inanc","family":"Birol","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2019,12,24]]},"references-count":60,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,4,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btz949","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/637710","asserted-by":"object"}]},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,4,15]]},"published":{"date-parts":[[2019,12,24]]}}}