title: Long non-coding RNA identification over mouse brain development by integrative modeling of chromatin and genomic features.
abstract: In silico prediction of genomic long non-coding RNAs (lncRNAs) is prerequisite to the construction and elucidation of non-coding regulatory network. Chromatin modifications marked by chromatin regulators are important epigenetic features, which can be captured by prevailing high-throughput approaches such as ChIP sequencing. We demonstrate that the accuracy of lncRNA predictions can be greatly improved when incorporating high-throughput chromatin modifications over mouse embryonic stem differentiation toward adult Cerebellum by logistic regression with LASSO regularization. The discriminating features include H3K9me3, H3K27ac, H3K4me1, open reading frames and several repeat elements. Importantly, chromatin information is suggested to be complementary to genomic sequence information, highlighting the importance of an integrated model. Applying integrated model, we obtain a list of putative lncRNAs based on uncharacterized fragments from transcriptome assembly. We demonstrate that the putative lncRNAs have regulatory roles in vicinity of known gene loci by expression and Gene Ontology enrichment analysis. We also show that the lncRNA expression specificity can be efficiently modeled by the chromatin data with same developmental stage. The study not only supports the biological hypothesis that chromatin can regulate expression of tissue-specific or developmental stage-specific lncRNAs but also reveals the discriminating features between lncRNA and coding genes, which would guide further lncRNA identifications and characterizations.
authors.affiliation: School of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001, China and College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lv
authors.forename: Hongbo
authors.initials: H
authors.lastname: Liu
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Huang
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Su
authors.forename: Hongjuan
authors.initials: H
authors.lastname: He
authors.forename: Youcheng
authors.initials: Y
authors.lastname: Xiu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D023281:Genomics; D016015:Logistic Models; D051379:Mice; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D002843:Chromatin; D062085:RNA, Long Noncoding
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