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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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Function annotation of human lincRNAs. (a) flowchart of co-expression association annotation. Expression profile across hES and 16 human adult tissues was filtered for low expressed genes. Then, Gini correlations were calculated and neighbors of each lincRNA were selected to do GO enrichment analysis. We got a list of enriched GO slim terms and their corresponding lincRNAs by mapping GO terms to GO slim terms. Finally, we did Fisher's exact test to test whether interested lincRNA sets were enriched in each GO slim terms. Please see details in GO enrichment analysis section in Data Preparation of Methods and Materials. (b) Significantly enriched biological processes of hES lincRNAs, (c) hES biased lincRNAs.
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Figure 2: Function annotation of human lincRNAs. (a) flowchart of co-expression association annotation. Expression profile across hES and 16 human adult tissues was filtered for low expressed genes. Then, Gini correlations were calculated and neighbors of each lincRNA were selected to do GO enrichment analysis. We got a list of enriched GO slim terms and their corresponding lincRNAs by mapping GO terms to GO slim terms. Finally, we did Fisher's exact test to test whether interested lincRNA sets were enriched in each GO slim terms. Please see details in GO enrichment analysis section in Data Preparation of Methods and Materials. (b) Significantly enriched biological processes of hES lincRNAs, (c) hES biased lincRNAs.

Mentions: Largely due to the elusive nature of lincRNA functional mechanism, it's still hardly practical to infer functions of lincRNAs from their nucleotide sequences solely [24]. Thus, we tried to annotate lincRNAs based on co-expression association strategy [15,25]. In brief, for each lincRNA, we firstly identified protein coding genes with strong expression correlation ("neighbors"), and assigned the corresponding Gene Ontology (GO) terms of these neighbors as the annotations of this lincRNA. To get an overview, fine-grained terms were further projected onto generic Gene Ontology slim (GO slim) terms (see Methods and Materials for more details). Finally, we successfully annotated more than 96% (1,765 out of 1,826) expressed lincRNAs (Figure 2a).


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)

Function annotation of human lincRNAs. (a) flowchart of co-expression association annotation. Expression profile across hES and 16 human adult tissues was filtered for low expressed genes. Then, Gini correlations were calculated and neighbors of each lincRNA were selected to do GO enrichment analysis. We got a list of enriched GO slim terms and their corresponding lincRNAs by mapping GO terms to GO slim terms. Finally, we did Fisher's exact test to test whether interested lincRNA sets were enriched in each GO slim terms. Please see details in GO enrichment analysis section in Data Preparation of Methods and Materials. (b) Significantly enriched biological processes of hES lincRNAs, (c) hES biased lincRNAs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Function annotation of human lincRNAs. (a) flowchart of co-expression association annotation. Expression profile across hES and 16 human adult tissues was filtered for low expressed genes. Then, Gini correlations were calculated and neighbors of each lincRNA were selected to do GO enrichment analysis. We got a list of enriched GO slim terms and their corresponding lincRNAs by mapping GO terms to GO slim terms. Finally, we did Fisher's exact test to test whether interested lincRNA sets were enriched in each GO slim terms. Please see details in GO enrichment analysis section in Data Preparation of Methods and Materials. (b) Significantly enriched biological processes of hES lincRNAs, (c) hES biased lincRNAs.
Mentions: Largely due to the elusive nature of lincRNA functional mechanism, it's still hardly practical to infer functions of lincRNAs from their nucleotide sequences solely [24]. Thus, we tried to annotate lincRNAs based on co-expression association strategy [15,25]. In brief, for each lincRNA, we firstly identified protein coding genes with strong expression correlation ("neighbors"), and assigned the corresponding Gene Ontology (GO) terms of these neighbors as the annotations of this lincRNA. To get an overview, fine-grained terms were further projected onto generic Gene Ontology slim (GO slim) terms (see Methods and Materials for more details). Finally, we successfully annotated more than 96% (1,765 out of 1,826) expressed lincRNAs (Figure 2a).

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