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miFRame: analysis and visualization of miRNA sequencing data in neurological disorders

Backes, Christina, Haas, Jan, Leidinger, Petra, Frese, Karen, Großmann, Thomas, Ruprecht, Klemens, Meder, Benjamin, Meese, Eckart, Keller, Andreas·2015·Journal of Translational Medicine
DOI 10.1186/s12967-015-0594-xPMC PMC4501052
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Figures

Figure 1 miFRame workflow. The figure sketches the three-layered workflow of miFRame. First, NGS data have to be uploaded along with a parameter set, next statistical analyses are carried out and finally, results are presented to the user.
Figure 1 miFRame workflow. The figure sketches the three-layered workflow of miFRame. First, NGS data have to be uploaded along with a parameter set, next statistical analyses are carried out and finally, results are presented to the user.CC BY · PubMed Central
Figure 2 Manhattan plots. The results of the expression analysis for MS and AD are presented. Each microRNA included in the set is located on the genome (x-axis) and for this miRNA the negative decade logarithm is presented on the y-axis. The higher the respective data points, the more significant the results are. The graphic reveals that the AD study showed increased significance as compared to the MS study (scale on the y-axis).
Figure 2 Manhattan plots. The results of the expression analysis for MS and AD are presented. Each microRNA included in the set is located on the genome (x-axis) and for this miRNA the negative decade logarithm is presented on the y-axis. The higher the respective data points, the more significant the results are. The graphic reveals that the AD study showed increased significance as compared to the MS study (scale on the y-axis).CC BY · PubMed Central
Figure 3 Pileup plot for miR-3150a-3p. The figure presents an extract of pileup plots for hsa-miR-3150a-3p in the two studies (a AD; b MS). Samples on top represent cases and on bottom controls. Each sample where at least a single read mapped to the precursor get an own line. The sequence in the middle corresponds to the precursor sequence, the mature miRNA (in this case the 3p mature form) is colored in red. The blue shaded area marks the mature part of this miRNA. In both cases, AD and MS, reads are partially mapping outside the mature form of this miRNA.
Figure 3 Pileup plot for miR-3150a-3p. The figure presents an extract of pileup plots for hsa-miR-3150a-3p in the two studies (a AD; b MS). Samples on top represent cases and on bottom controls. Each sample where at least a single read mapped to the precursor get an own line. The sequence in the middle corresponds to the precursor sequence, the mature miRNA (in this case the 3p mature form) is colored in red. The blue shaded area marks the mature part of this miRNA. In both cases, AD and MS, reads are partially mapping outside the mature form of this miRNA.CC BY · PubMed Central
Figure 4 Expression ratio of 3p and 5p mature forms. In this figure, opposite fold changes of the 3p and the 5p mature form of miRNAs is shown for two miRNAs, miR-3180 in panel a and miR-202 in panel b. The right part shows the pileup plots, the sequence in the middle represents the precursor, the two mature forms are highlighted in red (5p) and blue (3p) and with the blue shaded area. The right hand side shows the negative decade logarithm of the p-value for each single position. Up-regulated positions on the precursor in controls are colored in green and red bars correspond tow don-regulated positions on the precursor. The two red and green blocks correspond to the two mature forms, respectively. Clearly, the 3p form is up-regulated while the 5p form is down regulated for miR-3180 (panel a) while miR-202 shows the opposite behavior (panel b).
Figure 4 Expression ratio of 3p and 5p mature forms. In this figure, opposite fold changes of the 3p and the 5p mature form of miRNAs is shown for two miRNAs, miR-3180 in panel a and miR-202 in panel b. The right part shows the pileup plots, the sequence in the middle represents the precursor, the two mature forms are highlighted in red (5p) and blue (3p) and with the blue shaded area. The right hand side shows the negative decade logarithm of the p-value for each single position. Up-regulated positions on the precursor in controls are colored in green and red bars correspond tow don-regulated positions on the precursor. The two red and green blocks correspond to the two mature forms, respectively. Clearly, the 3p form is up-regulated while the 5p form is down regulated for miR-3180 (panel a) while miR-202 shows the opposite behavior (panel b).CC BY · PubMed Central
Figure 5 a Potential novel mature miRNA. The upper part of the figure presents the pileup plot (similar to Figures 3, 4). Just one mature form is annotated in miRBase V20, namely the 5p form (colored in red and shaded in blue). Nevertheless, many reads map to the position where a 3p version could be located. The lower right part shows the significant down-regulation of this miRNA in controls as compared to Alzheimer Disease patients. The lower left image presents beyond the significance the absolute rad count per sample. Green samples correspond to cases and red samples to controls. b For miR-4472, just one mature form (5p) is annotated in the miRBase. While we do not observe mappings to this position, we observe mappings to the position where the 3p mature form could be expected.
Figure 5 a Potential novel mature miRNA. The upper part of the figure presents the pileup plot (similar to Figures 3, 4). Just one mature form is annotated in miRBase V20, namely the 5p form (colored in red and shaded in blue). Nevertheless, many reads map to the position where a 3p version could be located. The lower right part shows the significant down-regulation of this miRNA in controls as compared to Alzheimer Disease patients. The lower left image presents beyond the significance the absolute rad count per sample. Green samples correspond to cases and red samples to controls. b For miR-4472, just one mature form (5p) is annotated in the miRBase. While we do not observe mappings to this position, we observe mappings to the position where the 3p mature form could be expected.CC BY · PubMed Central
Figure 6 potential isoforms of miR-30d-5p. The bar-plot on the right hand side shows increased significance at the edges of miR-30d-5p. In this case, Alzheimer Disease patients have higher expression on few base positions outside the annotated miRNA. This can be also seen on the read distribution plot on the right hand side. At position 26–29, Alzheimer Disease patients (green) have significantly higher coverage than controls.
Figure 6 potential isoforms of miR-30d-5p. The bar-plot on the right hand side shows increased significance at the edges of miR-30d-5p. In this case, Alzheimer Disease patients have higher expression on few base positions outside the annotated miRNA. This can be also seen on the read distribution plot on the right hand side. At position 26–29, Alzheimer Disease patients (green) have significantly higher coverage than controls.CC BY · PubMed Central
Figure 7 a Pileup plot for miR-1307. In case of miR-1307-5p, control patients show increased frequency of 1–2 base shifts at the 3p end. The pie diagram at the lower part of the figure shows that around one-third of all analyses revealed respective iso-forms. b Pileup plot for miR-3172. For miR-3127-3p, AD samples are frequently shifted by 1–2 bases to the 3p end of this miRNA. The pie chart as result of the aggregation analysis indicates that respective results are usually not observed. c Pileup plot for miR-378b. Extended mappings at the 3p end of this miRNA are almost exclusively observed for AD patients.
Figure 7 a Pileup plot for miR-1307. In case of miR-1307-5p, control patients show increased frequency of 1–2 base shifts at the 3p end. The pie diagram at the lower part of the figure shows that around one-third of all analyses revealed respective iso-forms. b Pileup plot for miR-3172. For miR-3127-3p, AD samples are frequently shifted by 1–2 bases to the 3p end of this miRNA. The pie chart as result of the aggregation analysis indicates that respective results are usually not observed. c Pileup plot for miR-378b. Extended mappings at the 3p end of this miRNA are almost exclusively observed for AD patients.CC BY · PubMed Central

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Citations

Cites

Research works printed but not linked: 17

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Metadata

Authors
Backes, C., Haas, J., Leidinger, P., Frese, K., Großmann, T., Ruprecht, K., Meder, B., Meese, E., & Keller, A.
Venue
Journal of Translational Medicine
Publisher
Springer Science and Business Media LLC
Published
2015-07-14
Volume
13
Issue
1
ISSN
1479-5876
DOI
10.1186/s12967-015-0594-x
PMC
PMC4501052
Cited by
11
References
1
Language
en

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