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. 2018 May 9;19(Suppl 2):112.
doi: 10.1186/s12864-018-4458-7.

Comprehensive Analysis of coding-lncRNA Gene Co-Expression Network Uncovers Conserved Functional lncRNAs in Zebrafish

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Free PMC article

Comprehensive Analysis of coding-lncRNA Gene Co-Expression Network Uncovers Conserved Functional lncRNAs in Zebrafish

Wen Chen et al. BMC Genomics. .
Free PMC article

Abstract

Background: Zebrafish is a full-developed model system for studying development processes and human disease. Recent studies of deep sequencing had discovered a large number of long non-coding RNAs (lncRNAs) in zebrafish. However, only few of them had been functionally characterized. Therefore, how to take advantage of the mature zebrafish system to deeply investigate the lncRNAs' function and conservation is really intriguing.

Results: We systematically collected and analyzed a series of zebrafish RNA-seq data, then combined them with resources from known database and literatures. As a result, we obtained by far the most complete dataset of zebrafish lncRNAs, containing 13,604 lncRNA genes (21,128 transcripts) in total. Based on that, a co-expression network upon zebrafish coding and lncRNA genes was constructed and analyzed, and used to predict the Gene Ontology (GO) and the KEGG annotation of lncRNA. Meanwhile, we made a conservation analysis on zebrafish lncRNA, identifying 1828 conserved zebrafish lncRNA genes (1890 transcripts) that have their putative mammalian orthologs. We also found that zebrafish lncRNAs play important roles in regulation of the development and function of nervous system; these conserved lncRNAs present a significant sequential and functional conservation, with their mammalian counterparts.

Conclusions: By integrative data analysis and construction of coding-lncRNA gene co-expression network, we gained the most comprehensive dataset of zebrafish lncRNAs up to present, as well as their systematic annotations and comprehensive analyses on function and conservation. Our study provides a reliable zebrafish-based platform to deeply explore lncRNA function and mechanism, as well as the lncRNA commonality between zebrafish and human.

Keywords: Co-expression network; Conservation; Gene ontology; KEGG; LncRNA; Zebrafish.

Conflict of interest statement

Ethics approval and consent to participate

No animals or other organisms were used in this study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Integration of all sources of zebrafish lncRNA. a Data sources and analysis pipeline. b The number of lncRNA transcripts from each source. c Venn diagram between different sources
Fig. 2
Fig. 2
Features of Zebrafish lncRNA. a Distribution of lncRNA subtypes. b Zebrafish lncRNA distribution in chromosomes. c Distribution of zebrafish lncRNA isoform number. d Distribution of zebrafish lncRNA exon number
Fig. 3
Fig. 3
Features of zebrafish coding-lncRNA gene co-expression network. a Cumulative distribution of gene expression Spearman’s correlation coefficient. b Network statistics by different correlation coefficient cutoffs. c Evaluation of function prediction performance of the network with different cutoffs. d Network degree distribution (correlation coefficient cutoff = 0.5)
Fig. 4
Fig. 4
Functional annotation of zebrafish lncRNAs. a LncRNA GO BP enrichment slim (top 10). b LncRNA KEGG pathway enrichment (top10). c Conserved lncRNA GO BP enrichment slim (top 10). d Conserved lncRNA KEGG pathway enrichment (top10)
Fig. 5
Fig. 5
Conservation analysis of zebrafish lncRNAs. a Cumulative distribution of conservation levels computed using PhastCons applied to the 8-way whole-genome. b Cumulative distribution of TSI (tissue specificity index). c Cumulative distribution of Spearman’s correlation coefficient of gene expression. d Cumulative distribution of TF families’ intersection over union score
Fig. 6
Fig. 6
ZFLNCG05544 is a candidate lncRNA gene related to human neuron diseases. a The two transcripts of ZFLNCG05544(ZFLNCT08573, ZFLNCT08573) and durga in UCSC genome browser. b ZFLNCG05544 co-expression subnetwork. c GO annotation of ZFLNCG05544 (top10). d KEGG annotation of ZFLNCG05544 (top10)
Fig. 7
Fig. 7
ZFLNCG08251 is a human MALAT1 homolog in zebrafish. a ZFLNCG08251 co-expression subnetwork. b. GO annotation of ZFLNCG08251 (top10). c KEGG annotation of ZFLNCG08251 (top10)

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