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Pathway analysis from lists of microRNAs: common pitfalls and alternative strategy.

Godard P, van Eyll J - Nucleic Acids Res. (2015)

Bottom Line: MicroRNAs (miRNAs) are involved in the regulation of gene expression at a post-transcriptional level.In large scale studies, once miRNAs of interest have been identified, the target genes they regulate are often inferred using algorithms or databases.A pathway analysis is then often performed in order to generate hypotheses about the relevant biological functions controlled by the miRNA signature.

View Article: PubMed Central - PubMed

Affiliation: IP & Science, Thomson Reuters, 5901 Priestly Drive, #200, Carlsbad, CA 92008, USA.

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Related in: MedlinePlus

Pathways associated to miRNA signatures when applying strategy 1. (a) AD-up S1 pathways, AD-down S1 pathways and pathways enriched in genes targeted by at least one miRNA according to mirTarBase. (b) Pathways enriched in genes targeted by at least one miRNA according to MetaBase, TargetScan or mirTarBase. Numbers in red correspond to KEGG pathways and those in blue to MetaBase pathways.
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Figure 2: Pathways associated to miRNA signatures when applying strategy 1. (a) AD-up S1 pathways, AD-down S1 pathways and pathways enriched in genes targeted by at least one miRNA according to mirTarBase. (b) Pathways enriched in genes targeted by at least one miRNA according to MetaBase, TargetScan or mirTarBase. Numbers in red correspond to KEGG pathways and those in blue to MetaBase pathways.

Mentions: The results with random selections of mirRNAs indicate that the whole list of miRNA targets is biased for a subset of biological functions. In order to test this hypothesis, an enrichment analysis was performed starting from the whole list of 1324 genes targeted by at least one miRNA in mirTarBase. 73 KEGG pathways are significantly enriched (FDR < 0.05) with these 1324 miRNA target genes and they mainly relate to cancer and cell cycle (Supplementary Table S2). Table 1 shows the 20 most significant ones. When compared to previous AD use case, it turned out that 37 out of 38 AD-up and 70 out of 73 AD-down S1 pathways are common to pathways non-specifically enriched in whole list of miRNA target genes (Figure 2a). This result shows that the targets available in mirTarBase are strongly biased for some KEGG pathways.


Pathway analysis from lists of microRNAs: common pitfalls and alternative strategy.

Godard P, van Eyll J - Nucleic Acids Res. (2015)

Pathways associated to miRNA signatures when applying strategy 1. (a) AD-up S1 pathways, AD-down S1 pathways and pathways enriched in genes targeted by at least one miRNA according to mirTarBase. (b) Pathways enriched in genes targeted by at least one miRNA according to MetaBase, TargetScan or mirTarBase. Numbers in red correspond to KEGG pathways and those in blue to MetaBase pathways.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4402548&req=5

Figure 2: Pathways associated to miRNA signatures when applying strategy 1. (a) AD-up S1 pathways, AD-down S1 pathways and pathways enriched in genes targeted by at least one miRNA according to mirTarBase. (b) Pathways enriched in genes targeted by at least one miRNA according to MetaBase, TargetScan or mirTarBase. Numbers in red correspond to KEGG pathways and those in blue to MetaBase pathways.
Mentions: The results with random selections of mirRNAs indicate that the whole list of miRNA targets is biased for a subset of biological functions. In order to test this hypothesis, an enrichment analysis was performed starting from the whole list of 1324 genes targeted by at least one miRNA in mirTarBase. 73 KEGG pathways are significantly enriched (FDR < 0.05) with these 1324 miRNA target genes and they mainly relate to cancer and cell cycle (Supplementary Table S2). Table 1 shows the 20 most significant ones. When compared to previous AD use case, it turned out that 37 out of 38 AD-up and 70 out of 73 AD-down S1 pathways are common to pathways non-specifically enriched in whole list of miRNA target genes (Figure 2a). This result shows that the targets available in mirTarBase are strongly biased for some KEGG pathways.

Bottom Line: MicroRNAs (miRNAs) are involved in the regulation of gene expression at a post-transcriptional level.In large scale studies, once miRNAs of interest have been identified, the target genes they regulate are often inferred using algorithms or databases.A pathway analysis is then often performed in order to generate hypotheses about the relevant biological functions controlled by the miRNA signature.

View Article: PubMed Central - PubMed

Affiliation: IP & Science, Thomson Reuters, 5901 Priestly Drive, #200, Carlsbad, CA 92008, USA.

Show MeSH
Related in: MedlinePlus