I was recently an external examiner for a PhD viva in Cambridge. As we were wrapping up, I asked “if you were to do it all again, what would you do differently?”. It’s one of my stock questions and normally the candidate says “oh I’d do it so much quicker!” or something similar. However, this time I got a surprise. “I would write my thesis in LaTeX!”, was the reply.
As a recent convert to LaTeX I could see where she was coming from. The last couple of manuscripts I have written were done in Overleaf and have been a breeze. This post is my summary of the site.
I have written ~40 manuscripts and countless other documents using Microsoft Word for Mac, with EndNote as a reference manager (although I have had some failed attempts to break free of that). I’d tried and failed to start using TeX last year, motivated by seeing nicely formatted preprints appearing online. A few months ago I had a new manuscript to write with a significant mathematical modelling component and I realised that now was the chance to make the switch. Not least because my collaborator said “if we are going to write this paper in Word, I wouldn’t know where to start”.
I signed up for an Overleaf account. For those that don’t know, Overleaf is an online TeX writing tool on one half of the screen and a rendered version of your manuscript on the other. The learning curve is quite shallow if you are used to any kind of programming or markup. There are many examples on the site and finding out how to do stuff is quick thanks to LaTeX wikibooks and stackexchange.
Beyond the TeX, the experience of writing a manuscript in Overleaf is very similar to editing a blog post in WordPress.
The best thing about Overleaf is the ability to collaborate easily. You can send a link to a collaborator and then work on it together. Using Word in this way can be done with DropBox, but versioning and track changes often cause more problems than it’s worth and most people still email Word versions to each other, which is a nightmare. Overleaf changes this by having a simple interface that can be accessed by multiple people. I have never used Google docs for writing papers, but this does offer the same functionality.
All projects are private by default, but you can put your document up on the site if you want to. You might want to do this if you have developed an example document in a certain style.
Depending on the type of account you have, you can roll back changes. It is possible to ‘save’ versions, so if you get to a first draft and want to send it round for comment, you can save a version and then use this to go back to, if required. This is a handy insurance in case somebody comes in to edit the document and breaks something.
You can download a PDF at any point, or for that matter take all the files away as a zip. No more finalfinalpaper3final.docx…
If you’re keeping score, that’s Overleaf 2, Word nil.
Placing figures in the text is easy and all major formats are supported. What is particularly nice is that I can generate figures in an Igor layout and output directly to PDF and put that into Overleaf. In Word, the placement of figures can be fiddly. Everyone knows the sensation of moving a picture slightly and it disappears inexplicably onto another page. LaTeX will put the figure in where you want it or the next best place. It just works.
This is what LaTeX excels at. Microsoft Word has an equation editor which has varied over the years from terrible to just-about-usable. The current version actually uses elements of TeX (I think). The support for mathematical text in LaTeX is amazing, not surprising since this is the way that most papers in maths are written. Any biologist will find their needs met here.
Templates and formatting
There are lots of templates available on Overleaf and many more on the web. For example, there are nice PNAS and PLoS formats as well as others for theses and for CVs and other documents. The typesetting is beautiful. Setting out sections/subsections and table of contents is easy. To be fair to Word, if you know how to use it properly, this is easy too, but the problem is that most people don’t, and also styles can get messed up too easily.
This works by adding a bibtex file to your project. You can do this with any reference manager. Because I have a huge EndNote database, I used this initially. Another manuscript I’ve been working on, my student started out with a Mendeley library and we’ve used that. It’s very flexible. Slightly more fiddly than with Word and EndNote. However, I’ve had so many problems (and crashes) with that combination over the years that any alternative is a relief.
You can set the view on the right to compile automatically or you can force updates manually. Either way the document must compile. If you have made a mistake, it will complain and try to guess what you have done wrong and tell you. Errors that prevent the document from being compiled are red. Less serious errors are yellow and allow compilation to go ahead. This can be slow going at first, but I found that I was soon up to speed with editing.
This is the name of the stuff at the header of a TeX document. You can add in all kinds of packages to cover proper usage of units (siunitx) or chemical notation (mhchem). They all have great documentation. All the basics, e.g. referencing, are included in Overleaf by default.
The entire concept of Overleaf is to work online. Otherwise you could just use TeXshop or some other program. But how about times when you don’t have internet access? I was concerned about this at the start, but I found that in practice, these days, times when you don’t have a connection are very few and far between. However, I was recently travelling and wanted to work on an Overleaf manuscript on the aeroplane. Of course, with Word, this is straightforward.
With Overleaf it is possible. You can do two things. The first is to download your files ahead of your period of internet outage. You can edit your main.tex document in an editor of your choice. The second option is more sophisticated. You can clone your project with git and then work on that local clone. The instructions of how to do that are here (the instructions, from 2015, say it’s in beta, but it’s fully working). You can work on your document locally and then push changes back to Overleaf when you have access once more.
OK. Nothing is perfect and I noticed that typos and grammatical errors are more difficult for me to detect in Overleaf. I think this is because I am conditioned with years of Word use. The dictionary is smaller than in Word and it doesn’t try to correct your grammar like word does (although this is probably a good thing!). Maybe I should try the rich text view and see if that helps. I guess the other downside is that the other authors need to know TeX rather than Word. As described above if you are writing with a mathematician, this is not a problem. For biologists though this could be a challenge.
Back to the PhD exam
I actually think that writing a thesis is probably a once-in-a-lifetime chance to understand how Microsoft Word (and EndNote) really works. The candidate explained that she didn’t trust Word enough to do everything right, so her thesis was made of several different documents that were fudged to look like one long thesis. I don’t think this is that unusual. She explained that she had used Word because her supervisor could only use Word and she had wanted to take advantage of the Review tools. Her heart had sunk when her supervisor simply printed out drafts and commented using a red pen, meaning that she could have done it all in LaTeX and it would have been fine.
I have been totally won over by Overleaf. It beats Microsoft Word in so many ways… I’ll stick to Word for grant applications and other non-manuscript documents, but I’m going to keep using it for manuscripts, with the exception of papers written with people who will only use Word.
The future of cell biology, even for small labs, is quantitative and computational. What does this mean and what should it look like?
My group is not there yet, but in this post I’ll describe where we are heading. The graphic below shows my current view of the ideal workflow for my lab.
The graphic is pretty self-explanatory, but to walk you through:
- A lab member sets up a microscopy experiment. We have standardised procedures/protocols in a lab manual and systems are in place so that reagents are catalogued to minimise error.
- Data goes straight from the microscope to the server (and backed-up). Images and metadata are held in a database and object identifiers are used for referencing in electronic lab notebooks (and for auditing).
- Analysis of the data happens with varying degrees of human intervention. The outputs of all analyses are processed automatically. Code for doing these steps in under version control using git (github).
- Post-analysis the processed outputs contain markers for QC and error checking. We can also trace back to the original data and check the analysis. Development of code happens here too, speeding up slow procedures via “software engineering”.
- Figures are generated using scripts which are linked to the original data with an auditable record of any modification to the image.
- Project management, particularly of paper writing is via trello. Writing papers is done using collaborative tools. Everything is synchronised to enable working from any location.
- This is just an overview and some details are missing, e.g. backup of analyses is done locally and via the server.
Just to reiterate, that my team are not at this point yet, but we are reasonably close. We have not yet implemented three of these things properly in my group, but in our latest project (via collaboration) the workflow has worked as described above.
The output is a manuscript! In the future I can see that publication of a paper as a condensed report will give way to making the data, scripts and analysis available, together with a written summary. This workflow is designed to allow this to happen easily, but this is the topic for another post.
Part of a series on the future of cell biology in quantitative terms.
We were asked to write a Preview piece for Developmental Cell. Two interesting papers which deal with the insertion of amphipathic helices in membranes to influence membrane curvature during endocytosis were scheduled for publication and the journal wanted some “front matter” to promote them.
Our Preview is paywalled – sorry about that – but I can briefly tell you why these two papers are worth a read.
The first paper – a collaboration between EMBL scientists led by Marko Kaksonen – deals with the yeast proteins Ent1 and Sla2. Ent1 has an ENTH domain and Sla2 has an ANTH domain. ENTH stands for Epsin N-terminal homology whereas ANTH means AP180 N-terminal homology. These two domains are known to bind membrane and in the case of ENTH to tubulate and vesiculate giant unilamellar vesicles (GUVs). Ent1 does this via an amphipathic helix “Helix 0” that inserts into the outer leaflet to bend the membrane. The new paper shows that Ent1 and Sla2 can bind together (regulated by PIP2) and that ANTH regulates ENTH so that it doesn’t make lots of vesicles, instead the two team up to make regular membrane tubules. The tubules are decorated with a regular “coat” of these adaptor proteins. This coat could prepattern the clathrin lattice. Also, because Sla2 links to actin, then actin can presumably pull on this lattice to help drive the formation of a new vesicle. The regular spacing might distribute the forces evenly over large expanses of membrane.
The second paper – from David Owen’s lab at CIMR in Cambridge – shows that CALM (a protein with an ANTH domain) actually has a secret Helix 0! They show that this forms on contact with lipid. CALM influences the size of clathrin-coated pits and vesicles, by influencing curvature. They propose a model where cargo size needs to be matched to vesicle size, simply due to the energetics of pit formation. The idea is that cells do this by regulating the ratio of AP2 to CALM.
The post title and the title of our Preview is taken from “Zero Tolerance” by Death from their Symbolic LP. I didn’t want to be outdone by these Swedish scientists who have been using Bob Dylan song titles and lyrics in their papers for years.
We have a new paper out! You can access it here.
The work was mainly done by Cristina Gutiérrez Caballero, a post-doc in the lab. We had some help from Selena Burgess and Richard Bayliss at the University of Leicester, with whom we have an ongoing collaboration.
The paper in a nutshell
We found that TACC3 binds the plus-ends of microtubules via an interaction with ch-TOG. So TACC3 is a +TIP.
What is a +TIP?
This is a term used to describe proteins that bind to the plus-ends of microtubules. Microtubules are a major component of the cell’s cytoskeleton. They are polymers of alpha/beta-tubulin that grow and shrink, a feature known as dynamic instability. A microtubule has polarity, the fast growing end is known as the plus-end, and the slower growing end is referred to as the minus-end. There are many proteins that bind to the plus-end and these are termed +TIPs.
OK, so what are TACC3 and ch-TOG?
They are two proteins found on the mitotic spindle. TACC3 is an acronym for transforming acidic coiled-coil protein 3, and ch-TOG stands for colonic hepatic tumour overexpressed gene. As you can tell from the names they were discovered due to their altered expression in certain human cancers. TACC3 is a well-known substrate for Aurora A kinase, which is an enzyme that is often amplified in cancer. The ch-TOG protein is thought to be a microtubule polymerase, i.e. an enzyme that helps microtubules grow. In the paper, we describe how TACC3 and ch-TOG stick together at the microtubule end. TACC3 and ch-TOG are at the very end of the microtubule, they move ahead of other +TIPs like “end-binding proteins”, e.g. EB3.
What is the function of TACC3 as a +TIP?
We think that TACC3 is piggybacking on ch-TOG while it is acting as a polymerase, but any biological function or consequence of this piggybacking was difficult to detect. We couldn’t see any clear effect on microtubule dynamics when we removed or overexpressed TACC3. We did find that loss of TACC3 affects how cells migrate, but this is not likely to be due to a change in microtubule dynamics.
I thought TACC3 and ch-TOG were centrosomal proteins…
In the paper we look again at this and find that there are different pools of TACC3, ch-TOG and clathrin (alone and in combination) and describe how they reside in different places in the cell. Although ch-TOG is clearly at centrosomes, we don’t find TACC3 at centrosomes, although it is on microtubules that cluster near the centrosomes at the spindle pole. TACC3 is often described as a centrosomal protein in lots of other papers, but this is quite misleading.
We were on the cover – whatever that means in the digital age! We imaged a cell expressing tagged EB3 proteins, EB3 is another +TIP. We coloured consecutive frames different colours and the result looked pretty striking. Biology Open picked it as their cover, which we were really pleased about. Our paper is AOP at the moment and so hopefully they won’t change their mind by the time it appears in the next issue.
This is the second paper that we have deposited as a preprint at bioRxiv (not counting a third paper that we preprinted after it was accepted). I was keen to preprint this particular paper because we became aware that two other groups had similar results following a meeting last summer. Strangely, a week or so after preprinting and submitting to a journal, a paper from a completely different group appeared with a very similar finding! We’d been “scooped”. They had found that the Xenopus homologue of TACC3 was a +TIP in retinal neuronal cultures. The other group had clearly beaten us to it, having submitted their paper some time before our preprint. The reviewers of our paper complained that our data was no longer novel and our paper was rejected. This was annoying because there were lots of novel findings in our paper that weren’t in theirs (and vice versa). The reviewers did make some other constructive suggestions that we incorporated into the manuscript. We updated our preprint and then submitted to Biology Open. One advantage of the preprinting process is that the changes we made can be seen by all. Biology Open were great and took a decision based on our comments from the other journal and the changes we had made in response to them. Their decision to provisionally accept the paper was made in four days. Like our last experience publishing in Biology Open, it was very positive.
Gutiérrez-Caballero, C., Burgess, S.G., Bayliss, R. & Royle, S.J. (2015) TACC3-ch-TOG track the growing tips of microtubules independently of clathrin and Aurora-A phosphorylation. Biol. Open doi:10.1242/bio.201410843.
Nwagbara, B. U., Faris, A. E., Bearce, E. A., Erdogan, B., Ebbert, P. T., Evans, M. F., Rutherford, E. L., Enzenbacher, T. B. and Lowery, L. A. (2014) TACC3 is a microtubule plus end-tracking protein that promotes axon elongation and also regulates microtubule plus end dynamics in multiple embryonic cell types. Mol. Biol. Cell 25, 3350-3362.
The post title is taken from the last track on The Orb’s U.F.Orb album.
This post is about a paper that was recently published. It was the result of a nice collaboration between me and Francisco López-Murcia and Artur Llobet in Barcelona.
The paper in a nutshell
The availability of clathrin sets a limit for presynaptic function
Clathrin is a three legged protein that forms a cage around membranes during endoctosis. One site of intense clathrin-mediated endocytosis (CME) is the presynaptic terminal. Here, synaptic vesicles need to be recaptured after fusion and CME is the main route of retrieval. Clathrin is highly abundant in all cells and it is generally thought of as limitless for the formation of multiple clathrin-coated structures. Is this really true? In a neuron where there is a lot of endocytic activity, maybe the limits are tested?
It is known that strong stimulation of neurons causes synaptic depression – a form of reversible synaptic plasticity where the neuron can only evoke a weak postsynaptic response afterwards. Is depression a vesicle supply problem?
What did we find?
We showed that clathrin availability drops during stimulation that evokes depression. The drop in availability is due to clathrin forming vesicles and moving away from the synapse. We mimicked this by RNAi, dropping the clathrin levels and looking at synaptic responses. We found that when the clathrin levels drop, synaptic responses become very small. We noticed that fewer vesicles are able to be formed and those that do form are smaller. Interestingly, the amount of neurotransmitter (acetylcholine) in the vesicles was much less than the volume of the vesicles as measured by electron microscopy. This suggests there is an additional sorting problem in cells with lower clathrin levels.
A third reviewer was called in (due to a split decision between Reviewers 1 and 2). He/she asked a killer question: all of our data could be due to an off-target effect of RNAi, could we do a rescue experiment? We spent many weeks to get the rescue experiment to work, but a second viral infection was too much for the cells and engineering a virus to express clathrin was very difficult. The referee also said: if clathrin levels set a limit for synaptic function, why don’t you just express more clathrin? Well, we would if we could! But this gave us an idea… why don’t we just put clathrin in the pipette and let it diffuse out to the synapses and rescue the RNAi phenotype over time? We did it – and to our surprise – it worked! The neurons went from an inhibited state to wild-type function in about 20 min. We then realised we could use the same method on normal neurons to boost clathrin levels at the synapse and protect against synaptic depression. This also worked! These killer experiments were a great addition to the paper and are a good example of peer review improving the paper.
Fran and Artur did almost all the experimental work. I did a bit of molecular biology and clathrin purification. Artur and I wrote the paper and put the figures together – lots of skype and dropbox activity.
Artur is a physiologist and his lab like to tackle problems that are experimentally very challenging – work that my lab wouldn’t dare to do – he’s the perfect collaborator. I have known Artur for years. We were postdocs in the same lab at the LMB in the early 2000s. We tried a collaborative project to inhibit dynamin function in adrenal chromaffin cells at that time, but it didn’t work out. We have stayed in touch and this is our first paper together. The situation in Spain for scientific research is currently very bad and it deteriorated while the project was ongoing. This has been very sad to hear about, but fortunately we were able to finish this project and we hope to work together more in the future.
We were on the cover!
Now the scientific literature is online, this doesn’t mean so much anymore, but they picked our picture for the cover. It is a single cell microculture expressing GFP that was stained for synaptic markers and clathrin. I changed the channels around for artistic effect.
J Neurosci is slightly different to other journals that I’ve published in recently (my only other J Neurosci paper was published in 2002). For the following reasons:
- No supplementary information. The journal did away with this years ago to re-introduce some sanity in the peer review process. This didn’t affect our paper very much. We had a movie of clathrin movement that would have gone into the SI at another journal, but we simply removed it here.
- ORCIDs for authors are published with the paper. This gives the reader access to all your professional information and distinguishes authors with similar names. I think this is a good idea.
- Submission fee. All manuscripts are subject to a submission fee. I believe this is to defray the costs of editorial work. I think this makes sense, although I’m not sure how I would feel if our paper had been rejected.
López-Murcia, F.J., Royle, S.J. & Llobet, A. (2014) Presynaptic clathrin levels are a limiting factor for synaptic transmission J. Neurosci., 34: 8618-8629. doi: 10.1523/JNEUROSCI.5081-13.2014
The post title is taken from “Outer Limits” a 7″ Single by Sleep ∞ Over released in 2010.
We have a new paper out! You can read it here.
I thought I would write a post on how this paper came to be and also about our first proper experience with preprinting.
Title of the paper: Non-specificity of Pitstop 2 in clathrin-mediated endocytosis.
In a nutshell: we show that Pitstop 2, a supposedly selective clathrin inhibitor acts in a non-specific way to inhibit endocytosis.
Background: The description of “pitstops” – small molecules that inhibit clathrin-mediated endocytosis – back in 2011 in Cell was heralded as a major step-forward in cell biology. And it really would be a breakthrough if we had ways to selectively switch off clathrin-mediated endocytosis. Lots of nasty things gain entry into cells by hijacking this pathway, including viruses such as HIV and so if we could stop viral entry this could prevent cellular infection. Plus, these reagents would be really handy in the lab for cell biologists.
The rationale for designing the pitstop inhibitors was that they should block the interaction between clathrin and adaptor proteins. Adaptors are the proteins that recognise the membrane and cargo to be internalised – clathrin itself cannot do this. So if we can stop clathrin from binding adaptors there should be no internalisation – job done! Now, in 2000 or so, we thought that clathrin binds to adaptors via a single site on its N-terminal domain. This information was used in the drug screen that identified pitstops. The problem is that, since 2000, we have found that there are four sites on the N-terminal domain of clathrin that can each mediate endocytosis. So blocking one of these sites with a drug, would do nothing. Despite this, pitstop compounds, which were shown to have a selectivity for one site on the N-terminal domain of clathrin, blocked endocytosis. People in the field scratched their hands at how this is possible.
A damning paper was published in 2012 from Julie Donaldson’s lab showing that pitstops inhibit clathrin-independent endocytosis as well as clathrin-mediated endocytosis. Apparently, the compounds affect the plasma membrane and so all internalisation is inhibited. Many people thought this was the last that we would hear about these compounds. After all, these drugs need to be highly selective to be any use in the lab let alone in the clinic.
Our work: we had our own negative results using these compounds, sitting on our server, unpublished. Back in February 2011, while the Pitstop paper was under revision, the authors of that study sent some of these compounds to us in the hope that we could use these compounds to study clathrin on the mitotic spindle. The drugs did not affect clathrin binding to the spindle (although they probably should have done) and this prompted us to check whether the compounds were working – they had been shipped all the way from Australia so maybe something had gone wrong. We tested for inhibition of clathrin-mediated endocytosis and they worked really well.
At the time we were testing the function of each of the four interaction sites on clathrin in endocytosis, so we added Pitstop 2 to our experiments to test for specificity. We found that Pitstop 2 inhibits clathrin-mediated endocytosis even when the site where Pitstops are supposed to bind, has been mutated! The picture shows that the compound (pink) binds where sequences from adaptors can bind. Mutation of this site doesn’t affect endocytosis, because clathrin can use any three of the other four sites. Yet Pitstop blocks endocytosis mediated by this mutant, so it must act elsewhere, non-specifically.
So the compounds were not as specific as claimed, but what could we do with this information? There didn’t seem enough to publish and I didn’t want people in the lab working on this as it would take time and energy away from other projects. Especially when debunking other people’s work is such a thankless task (why this is the case, is for another post). The Dutta & Donaldson paper then came out, which was far more extensive than our results and so we moved on.
A few things prompted me to write this work up. Not least, Yasmina had since shown that our mutations were sufficient to prevent AP-2 binding to clathrin. This result filled a hole in our work. These things were:
- People continuing to use pitstops in published work, without acknowledging that they may act non-specifically. The turning point was this paper, which was critical of the Dutta & Donaldson work.
- People outside of the field using these compounds without realising their drawbacks.
- AbCam selling this compound and the thought of other scientists buying it and using it on the basis of the original paper made me feel very guilty that we had not published our findings.
- It kept getting easier and easier to publish “negative results”. Journals such as Biology Open from Company of Biologists or PLoS ONE and preprint servers (see below) make this very easy.
Finally, it was a twitter conversation with Jim Woodgett convinced me that, when I had the time, I would write it up.
We have our own results on the non-specificity of pitstops – if only there was a good/easy way to publish it and get the data out there.
— Steve Royle (@clathrin) October 17, 2013
To which, he replied:
— Jim Woodgett (@jwoodgett) October 17, 2013
I added an acknowledgement to him in our paper! So that, together with the launch of bioRxiv, convinced me to get the paper online.
The Preprinting Experience
This paper was our first proper preprint. We had put an accepted version of our eLife paper on bioRxiv before it came out in print at eLife, but that doesn’t really count. For full disclosure, I am an affiliate of bioRxiv.
The preprint went up on 13th February and we submitted it straight to Biology Open the next day. I had to check with the Journal that it was OK to submit a deposited paper. At the time they didn’t have a preprint policy (although I knew that David Stephens had submitted his preprinted paper there and he told me their policy was about to change). Biology Open now accept preprinted papers – you can check which journals do and which ones don’t here.
My idea was that I just wanted to get the information into the public domain as fast as possible. The upshot was, I wasn’t so bothered about getting feedback on the manuscript. For those that don’t know: the idea is that you deposit your paper, get feedback, improve your paper then submit it for publication. In the end I did get some feedback via email (not on the bioRxiv comments section), and I was able to incorporate those changes into the revised version. I think next time, I’ll deposit the paper and wait one week while soliciting comments and then submit to a journal.
It was viewed quite a few times in the time while the paper was being considered by Biology Open. I spoke to a PI who told me that they had found the paper and stopped using pitstop as a result. I think this means getting the work out there was worth it after all.
Now it is out “properly” in Biology Open and anyone can read it.
Verdict: I was really impressed by Biology Open. The reviewing and editorial work were handled very fast. I guess it helps that the paper was very short, but it was very uncomplicated. I wanted to publish with Biology Open rather than PLoS ONE as the Company of Biologists support cell biology in the UK. Disclaimer: I am on the committee of the British Society of Cell Biology which receives funding from CoB.
Depositing the preprint at bioRxiv was easy and for this type of paper, it is a no-brainer. I’m still not sure to what extent we will preprint our work in the future. This is unchartered territory that is evolving all the time, we’ll see. I can say that the experience for this paper was 100% positive.
Dutta, D., Williamson, C. D., Cole, N. B. and Donaldson, J. G. (2012) Pitstop 2 is a potent inhibitor of clathrin-independent endocytosis. PLoS One 7, e45799.
Lemmon, S. K. and Traub, L. M. (2012) Getting in Touch with the Clathrin Terminal Domain. Traffic, 13, 511-9.
Stahlschmidt, W., Robertson, M. J., Robinson, P. J., McCluskey, A. and Haucke, V. (2014) Clathrin terminal domain-ligand interactions regulate sorting of mannose 6-phosphate receptors mediated by AP-1 and GGA adaptors. J Biol Chem. 289, 4906-18.
von Kleist, L., Stahlschmidt, W., Bulut, H., Gromova, K., Puchkov, D., Robertson, M. J., MacGregor, K. A., Tomilin, N., Pechstein, A., Chau, N. et al. (2011) Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell 146, 471-84.
Willox, A.K., Sahraoui, Y.M.E. & Royle, S.J. (2014) Non-specificity of Pitstop 2 in clathrin-mediated endocytosis Biol Open, doi: 10.1242/bio.20147955.
Willox, A.K., Sahraoui, Y.M.E. & Royle, S.J. (2014) Non-specificity of Pitstop 2 in clathrin-mediated endocytosis bioRxiv, doi: 10.1101/002675.
The post title is taken from ‘Into The Great Wide Open’ by Tom Petty and The Heartbreakers from the LP of the same name.
How long does it take to publish a paper?
The answer is – in our experience, at least – about 9 months.
That’s right, it takes about the same amount of time to have a baby as it does to publish a scientific paper. Discussing how we can make the publication process quicker is for another day. Right now, let’s get into the numbers.
The graphic shows the time taken from submission-to-publication for papers on which I am an author. I’m missing data for two papers (one from 1999 and one from 2002) and the Biol Open paper is published online but not yet “in print”, but mostly the information is complete. If you want to calculate this for your own papers; my advice would be to keep a spreadsheet of submission and decision dates as you go along… and archive your emails.
In the last analysis, a few people pointed out ways that the graphic could be improved, and I’ve now implemented these changes.
The graphic shows that the journey to publication is in four eras:
- Pre-time (before 0 on the x-axis): this is the time from first submission to the first journal. A dark time which involves rejection.
- Submission at the final journal (starting at time 0). Again, the orange periods are when the manuscript is with the journal and the green, when it is with us. Needless to say this green time is mainly spent doing experimental work (compare green periods for reviews and for papers)
- Acceptance! This is where the orange bar stops. The manuscript is then readied for publication (blank area).
- Published online. A purple period that ends with final publication in print.
Note that: i) the delays are more-or-less negated by preprinting provided deposition is before the first submission (grey line, for Biol Open paper), ii) these delay diagrams do not take into account the original drafting/rewriting cycle before the fist submission – nor the time taken to do the work!
So… how long does it take to publish a paper?
In the top right graph: the time from first submission to being published online is 250 days on average (median). This is shown by the blue bar. If we throw in the average time it takes to go from online to print (15 days) this gives 265 days. The average time for human gestation is 266 days. So it takes about the same amount of time to have a baby as it does to publish a paper! By contrast, reviews take only 121 days, equivalent to four lunar cycles (118 days).
My 2005 paper at Nature holds the record for the most protracted publication 399 days from submission to publication. The fastest publication is the most recent, our Biol Open paper was online 49 days after submission (it was also online 1 day before submission as a preprint).
In the bottom right graph: I added together the total time each paper was either with the journal, or with us, and plotted the average. The time from acceptance-to-publication online is shown stacked onto the “time with journal” column. You can see from this graphic that the lion’s share of the delay comes from revisions that we must do in order for a paper to be published. Multiple revisions and submissions also push these numbers up compared to the totals for reviews.
How representative are these numbers?
This is a small dataset at many different journals and so it is difficult to conclude much. With this analysis, I was hoping to identify ‘slow journals’ that we should avoid and also to think about our publication strategy (as much as a crap shoot can have a strategy). The whole process is stochastic and I don’t see any reason to change the way that we navigate the system. Having said this, I can’t see us doing any more methods/book chapters, as they are just so slow.
Just over half of our papers have some “pre-time”, i.e. they got rejected from at least one other journal before finding a home. A colleague of mine likes to say:
“if your paper is accepted at the first journal you send it to, you sent it to the wrong place”
One thing for sure is that publication takes a long time. And I don’t think our experience is uncommon. The pace of scientific publishing has been described as glacial by Leslie Vosshall and I don’t disagree with this. I think the 9 months figure is probably representative for most areas of biology. I know that other scientists in my field, who have more tenacity for rejections and for slugging it out at high impact journals, have much longer times from 1st submission to acceptance. In my opinion, wasting even more time chasing publication is crazy, counter-productive and demotivating for the people in the lab.
The irony in all this is that, even though we are working at the absolute bleeding edge of science with all of this technology at our disposal, our methods for reporting science are badly out of date. And with that I’ll push the “publish” button and this will be online…
The title of this post comes from ‘Some Things Last A Long Time’ by Daniel Johnston from his LP ‘1990’.
How long does it take to publish a paper?
I posted the picture below on Twitter to show how long it takes for us to publish a paper.
The answer is 235 days. This is the median time from submission at the first journal to publication online or in print. The data are from our last ten papers.
The infographic proved popular with 40 retweets and 22 favourites. It was pointed out to me that the a few things would improve this visualisation:
1. Showing the names of the journals
2. Showing when the 1st submission was relative to the 1st submission at the journal that finally accepted the paper
3. What about reviews and other types of publication.
I am working on updating the graph to show all of these things… watch this space.
My point was really to show (perhaps to non-scientists) how long the process of publishing a paper can be. There is other information that can be gleaned from this, e.g. what proportion of time is at the journal’s side and how much is at our end?
The people who are eager to see which journals perform badly (slowly) will be disappointed: this is a very small subset of papers from one lab. I’d be interested in scraping the information on journal tardiness on a larger scale and synthesising this so that it can inform journal choice. Recently though major publishers have taken steps to make this information less accessible so don’t hold your breath.
The title of this post is from So Long by Cian Ciarán from the LP ‘Outside In’