- Martin Mann, Mostafa M Mohamed, Syed M Ali, and Rolf Backofen
Interactive implementations of thermodynamics-based RNA structure and RNA-RNA interaction prediction approaches for example-driven teaching
PLOS Computational Biology, 14 (8), e1006341, 2018. - Martin Raden, Syed M Ali, Omer S Alkhnbashi, Anke Busch, Fabrizio Costa, Jason A Davis, Florian Eggenhofer, Rick Gelhausen, Jens Georg, Steffen Heyne, Michael Hiller, Kousik Kundu, Robert Kleinkauf, Steffen C Lott, Mostafa M Mohamed, Alexander Mattheis, Milad Miladi, Andreas S Richter, Sebastian Will, Joachim Wolff, Patrick R Wright, and Rolf Backofen
Freiburg RNA tools: a central online resource for RNA-focused research and teaching
Nucleic Acids Research, 46(W1), W25-W29, 2018.
Teaching - accessibility : of interacting sites source at github@BackofenLab/RNA-Playground
State-of-the-art RNA-RNA interaction prediction algorithms take
the accessibility of the interacting regions into account. That is,
a penalty corrects the interaction scoring for how
much the interaction sites are involved in intramolecular base pairs.
This can be expressed by reverting unpaired probabilities $P^{u}_{i,j}$ into
pseudo energy scores via $-RT\log(P^{u}_{i,j})$ that represent the amount
of energy (within the structure ensemble) to unfold a region $i..j$
in order to make it accessible for intermolecular RNA-RNA interactions
(Ulrike Mückstein et al., 2006).
Here, we extend the hybrid-only approach towards the integration of an accessibility-based scoring. To this end, the simplified McCaskill approach is used to compute unpaired probabilities $P^{u}$. The penalties are used in a post-processing step to correct the hybridization energies in order to identify the interaction that optimizes the combination of hybridization and accessibility scoring.
Here, we extend the hybrid-only approach towards the integration of an accessibility-based scoring. To this end, the simplified McCaskill approach is used to compute unpaired probabilities $P^{u}$. The penalties are used in a post-processing step to correct the hybridization energies in order to identify the interaction that optimizes the combination of hybridization and accessibility scoring.
RNA sequence $S^1$:
RNA sequence $S^2$:
(Computation uses reversed sequence $\overleftarrow{S^2}$)
(Computation uses reversed sequence $\overleftarrow{S^2}$)
Minimal loop length $l$:
Energy weight of base pair $E_{bp}$:
'Normalized' temperature $RT$:
The following recursions are used to compute the interactions that
show an optimal combination of hybridization and accessibility.
To this end, first the maximal number of base pairs $D^{i,k}_{j,l}$ for all
interaction sites are computed using the
hybrid-only approach.
Furthermore, the unpaired probabilities $P^{u1}$ and $P^{u2}$ are
tabularized for both sequences $S^1$ and $\overleftarrow{S^2}$, resp., using the
simplified McCaskill approach.
Given these values, the accessibility-incorporating interaction scorings are computed and stored in table $I$. A non-zero entry $I^{i,k}_{j,l}$ represents the combined scoring for an interaction of $S^1_{i..k}$ with $\overleftarrow{S^2_{j..l}}$ with left/right most base pairs $(S^1_i,\overleftarrow{S^2_j})$/$(S^1_k,\overleftarrow{S^2_l})$, respectively.
Given these values, the accessibility-incorporating interaction scorings are computed and stored in table $I$. A non-zero entry $I^{i,k}_{j,l}$ represents the combined scoring for an interaction of $S^1_{i..k}$ with $\overleftarrow{S^2_{j..l}}$ with left/right most base pairs $(S^1_i,\overleftarrow{S^2_j})$/$(S^1_k,\overleftarrow{S^2_l})$, respectively.
Visualization of interacting base pairs (selected structure)
Due to the four-dimensionality of $I$, we only list the optimal
hybrid structures (up to 15). On selection, the intermolecular base pairs are
visualized. If all entries $I^{i,k}_{j,l}$ show negative scores,
no favorable interaction is possible since intramolecular base pairs
dominate the individual structures (too hight penalties for
possible interaction sites). Therefore, the structure list might be
empty.
| Possible Structures |
|---|
Energy of selection:
The box provides an ASCII representation of the interacting
base pairs of the selected structure with $S^{1}$ on top and $S^{2}$
on the bottom.
Note, sequence $S^{2}$ is reversed (running from right ($5'$) to left
($3'$)) within this representation.
Note further, if no interacting
base pairs are present, no visualization is done.
Accessibility
The simplified McCaskill approach
is used in order to compute the unpaired probabilities $P^{u}$ for each of
the two sequences. Please refer to the according page for details.
These are used to compute according energy penalties $ED$ to make an
interacting site $i..j$ accessible, i.e. $ED_{i,j} = -RT\cdot\log(P^{u}_{i,j})$.
In the following, the penalties for $S^1$ and $\overleftarrow{S^2}$ are
visualized in dotplot format, i.e. the larger the dot the higher is
the penalty for the respective subsequence to form an interaction.
Penalties $ED^{1}$ to make site in $S^{1}$ accessible:
Penalties $ED^{2}$ to make site in $\overleftarrow{S^2}$ accessible:
When using our resources please cite :
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