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Systematically profiling and annotating long intergenic non-coding RNAs in human embryonic stem cell.

Tang X, Hou M, Ding Y, Li Z, Ren L, Gao G - BMC Genomics (2013)

Bottom Line: To facilitate further investigation of these hES lincRNAs, we constructed an online portal for biologists to access all their sequences and annotations interactively.In addition to navigation through a genome browse interface, users can also locate lincRNAs through an advanced query interface based on both keywords and expression profiles, and analyze results through multiple tools.By integrating multiple RNA-Seq datasets, we systematically characterized and annotated 300 hES lincRNAs.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: While more and more long intergenic non-coding RNAs (lincRNAs) were identified to take important roles in both maintaining pluripotency and regulating differentiation, how these lincRNAs may define and drive cell fate decisions on a global scale are still mostly elusive. Systematical profiling and comprehensive annotation of embryonic stem cells lincRNAs may not only bring a clearer big picture of these novel regulators but also shed light on their functionalities.

Results: Based on multiple RNA-Seq datasets, we systematically identified 300 human embryonic stem cell lincRNAs (hES lincRNAs). Of which, one forth (78 out of 300) hES lincRNAs were further identified to be biasedly expressed in human ES cells. Functional analysis showed that they were preferentially involved in several early-development related biological processes. Comparative genomics analysis further suggested that around half of the identified hES lincRNAs were conserved in mouse. To facilitate further investigation of these hES lincRNAs, we constructed an online portal for biologists to access all their sequences and annotations interactively. In addition to navigation through a genome browse interface, users can also locate lincRNAs through an advanced query interface based on both keywords and expression profiles, and analyze results through multiple tools.

Conclusions: By integrating multiple RNA-Seq datasets, we systematically characterized and annotated 300 hES lincRNAs. A full functional web portal is available freely at http://scbrowse.cbi.pku.edu.cn. As the first global profiling and annotating of human embryonic stem cell lincRNAs, this work aims to provide a valuable resource for both experimental biologists and bioinformaticians.

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300 hES lincRNAs. (a) The analysis pipeline. We mapped reads onto hg19 human genome using TopHat (v1.4.1) [39] with a reference helped strategy in case of failure to map some junction reads. We merged gene models from different resources using cuffcompare, and calculated gene expression level using Cufflinks (v2.0.2) [17] based on gene models we compiled. (b) Abundance of 300 hES lincRNAs across hES and human adult tissues. Color intensity represents the fractional density across the row of FPKM as estimated by Cufflinks [17]. Classifying by tissue specificity index [46], one fourth (78 out of 300) hES lincRNAs were biasedly expressed in hES (tau > 0.9).
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Figure 1: 300 hES lincRNAs. (a) The analysis pipeline. We mapped reads onto hg19 human genome using TopHat (v1.4.1) [39] with a reference helped strategy in case of failure to map some junction reads. We merged gene models from different resources using cuffcompare, and calculated gene expression level using Cufflinks (v2.0.2) [17] based on gene models we compiled. (b) Abundance of 300 hES lincRNAs across hES and human adult tissues. Color intensity represents the fractional density across the row of FPKM as estimated by Cufflinks [17]. Classifying by tissue specificity index [46], one fourth (78 out of 300) hES lincRNAs were biasedly expressed in hES (tau > 0.9).

Mentions: We then estimated their expression levels across 19 wild-type hES samples and 16 normal adult tissue samples with the standard FPKM (Fragments Per Kilobase of transcript per Million mapped reads) index [17] (Figure 1a). In case of over-representation of hES samples, we took the median values as a representative expression index. Noticeably, only one third (1,826 out of 5,576) lincRNAs were found to be expressed in at least one tissue (i.e. FPKM >= 1), much lower than protein-coding genes (Single-tailed Fisher's exact test, odds ratio = 0.058, p-value < 2.2e-16), suggesting a higher temporal-space expression specificity of lincRNAs than of protein-coding ones [18,19].


Systematically profiling and annotating long intergenic non-coding RNAs in human embryonic stem cell.

Tang X, Hou M, Ding Y, Li Z, Ren L, Gao G - BMC Genomics (2013)

300 hES lincRNAs. (a) The analysis pipeline. We mapped reads onto hg19 human genome using TopHat (v1.4.1) [39] with a reference helped strategy in case of failure to map some junction reads. We merged gene models from different resources using cuffcompare, and calculated gene expression level using Cufflinks (v2.0.2) [17] based on gene models we compiled. (b) Abundance of 300 hES lincRNAs across hES and human adult tissues. Color intensity represents the fractional density across the row of FPKM as estimated by Cufflinks [17]. Classifying by tissue specificity index [46], one fourth (78 out of 300) hES lincRNAs were biasedly expressed in hES (tau > 0.9).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852230&req=5

Figure 1: 300 hES lincRNAs. (a) The analysis pipeline. We mapped reads onto hg19 human genome using TopHat (v1.4.1) [39] with a reference helped strategy in case of failure to map some junction reads. We merged gene models from different resources using cuffcompare, and calculated gene expression level using Cufflinks (v2.0.2) [17] based on gene models we compiled. (b) Abundance of 300 hES lincRNAs across hES and human adult tissues. Color intensity represents the fractional density across the row of FPKM as estimated by Cufflinks [17]. Classifying by tissue specificity index [46], one fourth (78 out of 300) hES lincRNAs were biasedly expressed in hES (tau > 0.9).
Mentions: We then estimated their expression levels across 19 wild-type hES samples and 16 normal adult tissue samples with the standard FPKM (Fragments Per Kilobase of transcript per Million mapped reads) index [17] (Figure 1a). In case of over-representation of hES samples, we took the median values as a representative expression index. Noticeably, only one third (1,826 out of 5,576) lincRNAs were found to be expressed in at least one tissue (i.e. FPKM >= 1), much lower than protein-coding genes (Single-tailed Fisher's exact test, odds ratio = 0.058, p-value < 2.2e-16), suggesting a higher temporal-space expression specificity of lincRNAs than of protein-coding ones [18,19].

Bottom Line: To facilitate further investigation of these hES lincRNAs, we constructed an online portal for biologists to access all their sequences and annotations interactively.In addition to navigation through a genome browse interface, users can also locate lincRNAs through an advanced query interface based on both keywords and expression profiles, and analyze results through multiple tools.By integrating multiple RNA-Seq datasets, we systematically characterized and annotated 300 hES lincRNAs.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: While more and more long intergenic non-coding RNAs (lincRNAs) were identified to take important roles in both maintaining pluripotency and regulating differentiation, how these lincRNAs may define and drive cell fate decisions on a global scale are still mostly elusive. Systematical profiling and comprehensive annotation of embryonic stem cells lincRNAs may not only bring a clearer big picture of these novel regulators but also shed light on their functionalities.

Results: Based on multiple RNA-Seq datasets, we systematically identified 300 human embryonic stem cell lincRNAs (hES lincRNAs). Of which, one forth (78 out of 300) hES lincRNAs were further identified to be biasedly expressed in human ES cells. Functional analysis showed that they were preferentially involved in several early-development related biological processes. Comparative genomics analysis further suggested that around half of the identified hES lincRNAs were conserved in mouse. To facilitate further investigation of these hES lincRNAs, we constructed an online portal for biologists to access all their sequences and annotations interactively. In addition to navigation through a genome browse interface, users can also locate lincRNAs through an advanced query interface based on both keywords and expression profiles, and analyze results through multiple tools.

Conclusions: By integrating multiple RNA-Seq datasets, we systematically characterized and annotated 300 hES lincRNAs. A full functional web portal is available freely at http://scbrowse.cbi.pku.edu.cn. As the first global profiling and annotating of human embryonic stem cell lincRNAs, this work aims to provide a valuable resource for both experimental biologists and bioinformaticians.

Show MeSH