Hello all,
We had a teleconference today to discuss the feedback that we got
from Nature. The next call will be in one week,
Thursday 31st
at 4pm CET.
Action items:
- Everyone: by next week's call, please think/discuss within
your group what kind of future companion projects you are working
or are planning to launch based on Geuvadis data/samples.
- all who have added content to the wiki: please go through
the material that you have there: delete outdated content, and if
needed: add material and reorganize. Some missing content is
tolerable, incorrect information is not.
A brief summary of today's discussion:
- Manolis and myself have sent Nature's editor Magdalena Skipper a
rebuttal letter to address the points raised by the reviewers, and
the plan is to discuss with her soon. Let's hope that she will
give us the chance to revise the paper after all - we think that
there's a decent chance.
- On the call there was discussion of some of the most important
questions that the reviewers raised and the potential improvements
based on that (regardless of whether we'll resubmit to Nature or
to another journal). Depending on what happens with Nature, I'll
coordinate the details of the revisions later with the respective
people.
- Figure 1c raised questions but it's a pretty strong analysis
already. Include the splicing manuscript in the next submission
will show that we've worked on these questions in further depth
- data access: from the Geuvadis browser we'll provide
downloads of the full master files as well as regions. The Ensembl
broswer where the bams can be visualized doesn't have a slicing
functionality and it's well beyond our resources to start building
that. Tuuli will provide Natalja with a list of the final master
files of quantifications etc. that we'll want to share once the
paper is out.
- Jean is doing some additional analysis to estimate how
robust the transcript variation statistics are to lowly expressed
gene as well as lowly expressed transcripts of highly expressed
genes.
- In addition to transcript ratio QTLs, we could also do
polyadenylation QTLs - Pedro has quantified these already, and it
might add to the novelty of the paper and address the question of
variation in transcript structure.
- Regarding the robustness of the analysis, Peter had a good
idea of taking the old eQTLs from April (different mapper,
normalization and eQTL method, analysis by population) to show
that the results are highly overlapping (I believe and hope that
they are). We could also e.g. quantify 5 samples with Cufflinks
and show that flux is similar but better, or map to personalized
genomes, but we need to think very carefully how deep we want to
get into these types of analyses and how we'd interpret the
results before we do anything. Regarding allelic mapping bias, it
should be enough if we just describe Tuuli's existing analysis
better in the paper.
- One of the reviewers suggested that dropping some of the
analyses might improve the paper. I'm not keen to do that, but
we'll discuss this with Magdalena and if she wants us to do that,
that's what we'll do.
- Gabrielle created a visitor read-only access to the wiki so
that the reviewers can go and take a look.
So, now it's time to cross your fingers again and hope that our
letter convinces Magdalena to reconsider the rejection. We'll let
you know when have her decision.
best,
Tuuli
Tuuli Lappalainen, PhD
Department of Genetics, Stanford University School of Medicine , and
Department of Genetic Medicine and Development, University of Geneva
Email: tuuli.e.lappalainen@gmail.com / tlappala@stanford.edu
Tel: +1 415 351 9713
Bustamante lab
Department of Genetics
300 Pasteur Dr. Lane L301
Stanford, CA 94305-5120
USA
On /24/113 3:28 AM, Gabrielle Anne Bertier wrote:
Dear
all,
Here
are the details for the call:
TODAY
- Thursday 24th January at 16:00 CET
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SPAIN
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900800678
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GERMANY
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08001013982
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NETHERLANDS
|
08002658044
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FRANCE
|
0800947739
|
|
UNITED
KINGDOM
|
08005285280
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UNITED
STATES
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8005369053
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SWEDEN
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0201400578
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From
Other countries
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+34
917911859
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Thanks
alot,
Kind
regards,
Gabrielle
Gabrielle
Bertier
Scientific
Project Manager
International and Scientific Affairs
CRG, Center for Genomic Regulation
Carrer Dr. Aiguader, 88
08003 Barcelona, España
Tel: +34933160374
Mobile: +34639960656
email: gabrielle.bertier@crg.es
web: www.geuvadis.eu;
www.fliact.eu
Dear all,
The Geuvadis RNAseq paper was rejected this morning. We've
decided with Manolis that we should make an appeal, and we
have already been in touch with Magdalena about this. We'll
need to send her a response letter in a couple of days (see
the attachment with reviewer's comments and a rough response
draft). It ain't over til it's over.
Since we were going to have a call soon anyway, let's have a TC
on Thursday the 24th at 4pm CET. Before that, I'd be
happy to hear your comments to the response letter
(deadline: immediately). There's a couple of bigger
items to discuss, and specific questions to a few of you - see
below. There won't be a lot of new analysis to do if we're
given the chance to revise.
Questions:
- Do we drop non-essential analyses as #2 suggests? This would
mean RNA editing, maybe fusions and subtle splicing. I'm not
keen to, but if people think it would improve the overall
quality of the paper...
- Should we restructure the supplement by topic instead of
methods/figures/tables? Need to ask Magdalena too.
- Andrew & Natalja: Can we add a data slicing and download
function to the browser (or a separate site linked from the
browser)?
- Jean & Mar: How is the qualitative/quantitative analysis
affected by low-abundance transcripts? Will the results change
if the threshold is different?
- Jean, Mar, Pedro, Micha (and myself): #2 raises an important
question (really!): most of transcript variation is explained
by transcript ratio differences, but we find very few QTLs for
this. Why do you think this is? Is all that variation really
just random/environmental/epigenetic?
- Jean: #3 suspects that the 3% of transcriptome variation
explained by population could be just random - how do we
respond to this?
- Manny: What could we do to add novelty value to NMD
analysis?
- Gabrielle: Is it possible to make a read-only password for
the wiki? We could give one to the reviewers just so that they
can see it.
best regards,
Tuuli
--
Tuuli Lappalainen, PhD
Department of Genetics, Stanford University School of Medicine , and
Department of Genetic Medicine and Development, University of Geneva
Email: tuuli.e.lappalainen@gmail.com / tlappala@stanford.edu
Tel: +1 415 351 9713
Bustamante lab
Department of Genetics
300 Pasteur Dr. Lane L301
Stanford, CA 94305-5120
USA
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