{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:44:47Z","timestamp":1740185087042,"version":"3.37.3"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2018,9,9]],"date-time":"2018-09-09T00:00:00Z","timestamp":1536451200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21LM012619"],"award-info":[{"award-number":["R21LM012619"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007234","name":"University of Chicago","doi-asserted-by":"publisher","award":["1S10OD018495-01"],"award-info":[{"award-number":["1S10OD018495-01"]}],"id":[{"id":"10.13039\/100007234","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Therapeutically Applicable Research to Generate Effective Treatments"},{"name":"TARGET"},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["UlO CA98543"],"award-info":[{"award-number":["UlO CA98543"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Long intergenic noncoding RNAs (lincRNAs) have risen to prominence in cancer biology as new biomarkers of disease. Those lincRNAs transcribed from active cis-regulatory elements (enhancers) have provided mechanistic insight into cis-acting regulation; however, in the absence of an enhancer hallmark, computational prediction of cis-acting transcription of lincRNAs remains challenging. Here, we introduce a novel transcriptomic method: a cis-regulatory lincRNA\u2013gene associating metric, termed \u2018CisPi\u2019. CisPi quantifies the mutual information between lincRNAs and local gene expression regarding their response to perturbation, such as disease risk-dependence. To predict risk-dependent lincRNAs in neuroblastoma, an aggressive pediatric cancer, we advance this scoring scheme to measure lincRNAs that represent the minority of reads in RNA-Seq libraries by a novel side-by-side analytical pipeline.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Altered expression of lincRNAs that stratifies tumor risk is an informative readout of oncogenic enhancer activity. Our CisPi metric therefore provides a powerful computational model to identify enhancer-templated RNAs (eRNAs), eRNA-like lincRNAs, or active enhancers that regulate the expression of local genes. First, risk-dependent lincRNAs revealed active enhancers, over-represented neuroblastoma susceptibility loci, and uncovered novel clinical biomarkers. Second, the prioritized lincRNAs were significantly prognostic. Third, the predicted target genes further inherited the prognostic significance of these lincRNAs. In sum, RNA-Seq alone is sufficient to identify disease-associated lincRNAs using our methodologies, allowing broader applications to contexts in which enhancer hallmarks are not available or show limited sensitivity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The source code is available on request. The prioritized lincRNAs and their target genes are in the Supplementary Material.<\/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\/bty574","type":"journal-article","created":{"date-parts":[[2018,7,7]],"date-time":"2018-07-07T06:00:37Z","timestamp":1530943237000},"page":"i664-i670","source":"Crossref","is-referenced-by-count":1,"title":["CisPi: a transcriptomic score for disclosing cis-acting disease-associated lincRNAs"],"prefix":"10.1093","volume":"34","author":[{"given":"Zhezhen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Chicago, Chicago, IL, USA"}]},{"given":"John M","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chicago, Chicago, IL, USA"}]},{"given":"Xinan H","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chicago, Chicago, IL, USA"}]}],"member":"286","published-online":{"date-parts":[[2018,9,8]]},"reference":[{"key":"2023061313522521000_bty574-B1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1101\/gr.225755.117","article-title":"Enhancer RNA profiling predicts transcription factor activity","volume":"28","author":"Azofeifa","year":"2018","journal-title":"Genome Res"},{"key":"2023061313522521000_bty574-B2","doi-asserted-by":"crossref","first-page":"36572","DOI":"10.1038\/srep36572","article-title":"A comprehensive characterization of the function of LincRNAs in transcriptional regulation through long-range chromatin interactions","volume":"6","author":"Cai","year":"2016","journal-title":"Sci. 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