How should I cite predictions from this website?
Please cite the following (issue and page numbers will be
available shortly):
Schnall-Levin M, Zhao Y, Perrimon N, Berger
B. Conserved microRNA Targeting in Drosophila is as
Widespread in Coding Regions as in 3' UTRs.
PNAS Published online before print August 20, 2010,
doi: 10.1073/pnas.1006172107.
How are conserved sites determined? What do you mean by
'Probability of Conserved Targeting'?
Our model for judging conservation is described in our
paper above. Using a multi-species alignment, microRNA seed
sites are evaluated by the number of species they are
conserved to. This conservation is then scored according to
a context-specific background model and given a p-value.
The p-value gives the probability that the site would be
conserved as widely as it is, under the background model
where there is no additional selective pressure on the seed
site besides selection on the protein sequence and on codon
choice. Seed sites are classified as 'conserved' if the
p-value is below a cutoff value, chosen so that the false
positive rate on the set of conserved targets is below
50%.
In order to rank the confidence of target predictions, we
have modified the methodology of Friedman et al (Genome
Research (2009) 19:92-105), to produce a 'Probability of
Conserved Targeting' for each target transcript. The
'Probability of Conserved Targeting' takes into account the
number of sites in each transcript, the p-value for each
site (lower p-value means a higher 'Probability of Conserved
Targeting'), and the targeting microRNA (some microRNAs show
much greater evidence for conserved targeting than others).
The 'Probability of Conserved Targeting' gives our estimate
for the probability that at least one of the conserved seed
sites within a transcript (for a specific microRNA) has been
conserved due to selective pressure, and not merely by
chance.
How does microRNA targeting in the ORF compare to targeting
in the 3'UTR?
ORF targeting appears to generally be of weaker effect
than targeting in the 3'UTR, however a number of cases of
ORF targeting have already been demonstrated. We have seen
some evidence (both computationally and experimentally) that
the disparity between ORF targeting and 3'UTR targeting may
not be as strong in Drosophila as it is in mammals. Our
paper above contains additional discussion of microRNA
targeting in ORFs and references to previous work in this
area.
For the predictions in human, why are there only conserved 8-mers
and no conserved 7-mers?
The level of preferential conservation in humans is
smaller than in Drosophila and so the confidence of target
predictions is lower. While as a whole, 7-mer matches show
evidence for preferential conservation, the majority of
the sites cannot be predicted at high confidence. In
order to only retain target sites with high confidence, we
focused on those transcripts containing conserved 8-mers
and treated all 7-mers as non-conserved.
Who created the Minotar website?
The code for the site was written by Ian Flockhart.
You haven't answered my question. Who should I contact?
Please contact Michael Schnall-Levin (mschnall@mit.edu)
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