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MutaRNA 9510481

Input and runtime details for job 9510481 (precomputed example)

Sequence Parameters

? Wild type single RNA sequence in FASTA[.fa]
? Mutation encodingA101C

Folding options

? Window size (RNAplfold)200
? Maximal base pair span (RNAplfold)150

Job ID 9510481 (server version trunk)

?Job Submitted & Queued@ Tue Apr 14 17:50:58 CEST 2020
?MutaRNA Started@ Tue Apr 14 17:52:16 CEST 2020
?MutaRNA Finished & Post-Processing@ Tue Apr 14 17:57:58 CEST 2020
 DIRECT ACCESS: http://rna.informatik.uni-freiburg.de/RetrieveResults.jsp?jobID=9510481&toolName=MutaRNA ( 30 days expiry )

Description of the job

Revisiting mutation A30C in KRAS gene, which is known to increase gene expression (Sharma et al., 2019). Note, here mutation with sequence context +-100nt, i.e. mutation is at position 101. The loss of the first hairpin close to the RBS might explain the increased translation efficiency.

? Output download complete results [zip]

Folding results for mutation 'A101C'

Base pairing of wildtype vs. mutant A101C

The following visualizations provide a general overview on the base pairing potential of both the wildtype (WT) and SNP-mutated (mut) RNA sequence.
Base pair probabilities
Interactive via EasyPZ.js: - Zoom via mouse wheel or double left/right click - Panning via click-and-hold - Reset via page reload
[png] [svg]
Wildtype base pairs
Interactive via EasyPZ.js: - Zoom via mouse wheel or double left/right click - Panning via click-and-hold - Reset via page reload
[png] [svg]
Mutant base pairs
Interactive via EasyPZ.js: - Zoom via mouse wheel or double left/right click - Panning via click-and-hold - Reset via page reload
[png] [svg]
The dot plot (top-left) visualizes the base pairing potential of both the wildtype and the mutant RNA in a heatmap-like fashion. That is the darker the dot, the higher is the probability that the respective sequence positions form a base pair. Probabilities derived from the Boltzmann distributed energies of all structures that can be formed by an RNA given the folding constraints (e.g. maximal base pair span). The mutated position is highlighted by red dotted lines.
The same base pair probabilities are depicted via circular plots (top-left and -right) and arc plots (bottom-left and -right). Wildtype base pairing (top-middle) refers to the upper right part of the dot plot while mutant base pairing (top-right) covers information of the lower left part. In both, higher base pairing potential is reflected in darker hues of respective gray lines. The SNP position is marked by a red line in the outer ring within the mutant's plot on the right.
Arc plot representations (bottom) of the base pairing probabilities are analogous to the circular plots but use a heatmap-like arc coloring. That is highest probabilities are dark red while low probable base pairs are depicted in yellow.
Base pairing probabilities were extracted from the following dot plots: [WT.ps] [mut.ps] (RNAplfold (Bernhart et al., 2011)).
Wildtype vs. mutant base pair probabilities
Interactive via EasyPZ.js: - Zoom via mouse wheel or double left/right click - Panning via click-and-hold - Reset via page reload
[png] [svg]

Differential comparison for A101C

To better see the often local structural changes induced by a SNP mutation, the differences of the mutant's base pairing potential compared to the wildtype sequence are given below. Furthermore, the effects on the single-strandedness, i.e. accessibility, are visualized in terms of single-position unpaired probabilities within the structural ensembles.
Absolute change of base pair probabilities
Interactive via EasyPZ.js: - Zoom via mouse wheel or double left/right click - Panning via click-and-hold - Reset via page reload
[png] [svg] (full length [png] [svg])
Weakened base pairs
Interactive via EasyPZ.js: - Zoom via mouse wheel or double left/right click - Panning via click-and-hold - Reset via page reload
[png] [svg]
Increased base pairs
Interactive via EasyPZ.js: - Zoom via mouse wheel or double left/right click - Panning via click-and-hold - Reset via page reload
[png] [svg]
The dot plot (top-left) provides the absolute differences of the base pairing probabilities of SNP-mutated vs. wildtype RNA, i.e. in detail Pr(bp in WT) - Pr(bp in mut). The upper right part of (top-left) visualizes positive differences, i.e. a weakening of the base pairing potential, while the lower left reports (absolute values) of negative differences, i.e. base pairs with increased probability within the mutant. Again, darker hues reflect higher absolute changes. The mutated position is highlighted by red dotted lines.
In the (top-middle) and (top-right) respective visualizations are given in a circular plotting mode. Darker gray scales refer to higher absolute changes. The SNP position is annotated by a red bar in the outer ring.
Absolute change of base pair probabilities
Interactive via EasyPZ.js: - Zoom via mouse wheel or double left/right click - Panning via click-and-hold - Reset via page reload
[png] [svg] (full length [png] [svg])
Arc plot representations (top) of the absolute change of base pairing probabilities are analogous to the circular plots but use a heatmap-like arc coloring. That is highest probabilities are dark red while low probable base pairs are depicted in yellow. Weakened base pairs are shown on top while strengthened base pairs are depicted below the sequence. Mutations are highlighted by vertical dashed lines.
In case the effects are local, only the respective subsequence is shown. Full length depictions are available via respective links.
Base pair probability difference
Interactive via EasyPZ.js: - Zoom via mouse wheel or double left/right click - Panning via click-and-hold - Reset via page reload
[png] [svg] (full length [png] [svg])
Accessibility profiles ( interval length = )
Accessibility profiles
[png] [svg]
The dot plot (left) provides the differences of the base pairing probabilities of SNP-mutated vs. wildtype RNA, i.e. in detail Pr(bp in WT) - Pr(bp in mut). That is base pairs weakened by the mutation are in blue while higher base pair probability in the mutant are depicted in red. The mutated position is highlighted by red dotted lines.
The (right) accessibility profiles of both sequences and their differences provide an assessment of the mutation's effect on the RNA's single-strandedness, which is e.g. strongly related to its interaction potential with other RNAs or proteins. Accessibility is measured in terms of local single-position unpaired probabilities (RNAplfold (Bernhart et al., 2011)); extracted from the following files: [WT.txt] [mut.txt] The mutated position is highlighted by a red line.

Scoring of mutation 'A101C'

Assessment using remuRNA

Sort by selecting a column name.
SNP H(wt:mu) MFE(mu) MFE(wt) MFE delta
A101C 5.3870000000000005 -37.0 -37.7 -0.7
remuRNA (Salari et al., ‎2013) computes a localized relative entropy H(WT:mut) between the Boltzmann ensembles of the wildtype and the mutant RNAs around the SNP of interest. That way, effects of sequence length are reduced. The higher remuRNA's entropy value, the stronger is the structure impact of the SNP. If you use the score in your research, please also cite (Salari et al., ‎2013) along with the version information from below.
Since remuRNA supports only SNP encodings, each SNP is scored independently when multi-nucleotide mutations are provided as MutaRNA input.

Assessment using RNAsnp mode 1

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Assessment using RNAsnp mode 2

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RNAsnp (Sabarinathan et al., ‎2013) focuses on the local regions of maximal structural change between mutant and wildtype RNA. The mutation effects are quantified in terms of empirical P values. To this end, the RNAsnp software uses extensive precomputed tables of the distribution of SNP effects as function of length and GC content.
(Mode 1) is designed to predict the effect of SNPs on short RNA sequences (< 1000nts), where the base pair probabilities of the wildtype and mutant RNA sequences are calculated using the global folding method RNAfold. (distance) = the difference between the base pair probabilities of wildtype and mutant computed as Euclidean base pair distance. Finally, the interval with maximum base pairing distance or minimum correlation coefficient and the corresponding p-value is reported.
(Mode 2) is designed to predict the effect of SNPs on large RNA sequence using the local folding method RNAplfold with the default parameters -W 200 and -L 120. As a first step, the structural difference is calculated using the Euclidean distance measure for all sequence intervals of fixed window length. In the second step, the sequence interval with maximum base pair distance is selected to re-compute the difference for all internal local intervals. The interval with maximum base pair distance and the corresponding p-value is reported.
RNAsnp might provide additional warnings or error messages e.g. for very short sequences, which are available below the table if reported. For further details, we refer to the Help page of RNAsnp. If you use the scores in your research, please also cite (Sabarinathan et al., ‎2013) along with the version information from below.

Job resubmission

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Feeds the job parameters to the input page to resubmit the job.

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When using MutaRNA please cite :

Results are computed with MutaRNA version 1.3.0 (using RNAplfold 2.4.14, remuRNA 1.0, RNAsnp 1.2)