Long non-coding RNA identification over mouse brain development by integrative modeling of chromatin and genomic features.

Long non-coding RNA identification over mouse brain development by integrative modeling of chromatin and genomic features.
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通过染色质和基因组特征的综合建模对小鼠大脑发育进行长非编码RNA鉴定

DOI:
10.1093/nar/gkt818
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发表时间:
2013-12
影响因子:
14.9
通讯作者:
Wu Q
Wu Q
中科院分区:
生物学2区
文献类型:
--
作者:
Lv J;Liu H;Huang Z;Su J;He H;Xiu Y;Zhang Y;Wu Q

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在电子科学中,对基因组长非编码RNA的预测是构建和阐明非编码调控网络的前提。染色质调节剂标记的染色质修饰是重要的表观遗传特征,可以通过流行的高通量方法如芯片测序来捕捉。我们证明,通过Logistic回归和套索正则化,当结合高通量染色质修饰促进小鼠胚胎干细胞向成年小脑分化时,lncRNA预测的准确性可以大大提高。识别特征包括H3K9me3、H3K27ac、H3K4me1、开放阅读框和几个重复元件。重要的是,染色质信息被认为是基因组序列信息的补充,强调了综合模型的重要性。应用整合模型,我们从转录组组装中获得了一份基于未知片段的推测的LncRNAs列表。通过表达和基因本体论浓缩分析,我们证明了推测的lncRNAs在已知基因座附近具有调节作用。我们还表明,相同发育阶段的染色质数据可以有效地模拟lncRNA的表达特异性。该研究不仅支持染色质可以调节组织特异性或发育阶段特异性lncRNA表达的生物学假说,而且揭示了lncRNA和编码基因之间的区别特征,这将指导进一步的lncRNA鉴定和表征。
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.
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