Dividing Line: not so simple division in ctenophores

This wonderful movie has repeatedly popped up into my twitter feed.

It was taken by Tessa Montague and is available here (tweet is here).

The movie is striking because of the way that cytokinesis starts at one side and moves to the other. Most model systems for cell division have symmetrical division.

Rob de Bruin commented that “it makes total sense to segregate this way”. Implying that if a cell just gets cut in half it deals with equal sharing of components. This got me thinking…

It does make sense to share n identical objects this way. For example, vesiculation of the Golgi generates many equally sized vesicles. Cutting the cell in half ensures that each cell gets approximately half of the Golgi (although there is another pathway that actively segregates vesicular material, reviewed here). However, for segregation of genetic material – where it is essential that each cell receives one (and exactly one) copy of the genome – a cutting-in-half mechanism simply doesn’t cut it (pardon the pun).

The error rate of such a mechanism would be approximately 50% which is far too high for something so important. Especially at this (first) division as shown in the movie.

I knew nothing about ctenophores (comb jellies) before seeing this movie and with a bit of searching I found this paper. In here they show that there is indeed a karyokinetic (mitotic) mechanism that segregates the genetic material and that this happens independently of the cytokinetic process which is actin-dependent. So not so different after all. The asymmetric division and the fact that these divisions are very rapid and synchronised is very interesting. It’s very different to the sorts of cells that we study in the lab. Thanks to Tessa Montague for the amazing video that got me thinking about this.

Footnote: the 50% error rate can be calculated as follows. Although segregation is in 3D, this is a 1D problem. If we assume that the cell divides down the centre of the long axis and that object 1 and object 2 can be randomly situated along the long axis. There is an equal probability of each object ending each cell. So object 1 can end in either cell 1 or cell 2, as can object 2. The probability that objects 1 and 2 end in the same cell is 50%. This is because there is a 25% chance of each outcome (object 1 in cell 1, object 2 in cell 2; object 1 in cell 2, object 2 in cell 1; object 1 and object 2 in cell 1; object 1 and object 2 in cell 2). It doesn’t matter how many objects we are talking about or the size of the cell. This is a highly simplified calculation but serves the purpose of showing that another solution is needed to segregate objects with identity during cell division.

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The post title comes from “Dividing Line” from the Icons of Filth LP Onward Christian Soldiers.

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Frankly, Mr. Shankly

I read about Antonio Sánchez Chinchón’s clever approach to use the Travelling Salesperson algorithm to generate some math-art in R. The follow up was even nicer in my opinion, Pencil Scribbles. The subject was Boris Karloff as the monster in Frankenstein. I was interested in running the code (available here and here), so I thought I’d run it on a famous scientist.

By happy chance one of the most famous scientists of the 20th Century, Rosalind Franklin, shares a nominative prefix with the original subject. There is also a famous portrait of her that I thought would work well.

I first needed needed to clear up the background because it was too dark.

Now to run the TSP code.

The pencil scribbles version is nicer I think.

The R scripts basically ran out-of-the-box. I was using a new computer that didn’t have X11quartz on it nor the packages required, but once that they were installed I just needed to edit the line to use a local file in my working directory. The code just ran. The outputs FrankyTSP and Franky_scribbles didn’t even need to be renamed, given my subject’s name.

Thanks to Antonio for making the code available and so easy to use.

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The post title comes from “Frankly, Mr. Shankly” by The Smiths which appears on The Queen is Dead. If the choice of post title needs an explanation, it wasn’t a good choice…

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Paintball’s Coming Home: generating Damien Hirst spot paintings

A few days ago, I read an article about Damien Hirst’s new spot paintings. I’d forgotten how regular the spots were in the original spot paintings from the 1990s (examples are on his page here). It made me think that these paintings could be randomly generated and so I wrote a quick piece of code to do this (HirstGenerator).

I used Hirst’s painting ‘Abalone Acetone Powder’ (1991), which is shown on this page as photographed by Alex Hartley. A wrote some code to sample the colours of this image and then a script to replicate it. The original is shown below  © Damien Hirst and Science Ltd. Click them for full size.

and then this is the replica:

Now that I had a palette of the colours used in the original. It was simple to write a generator to make spot paintings where the spots are randomly assigned.

The generator can make canvasses at whatever size is required.

The code can be repurposed to make spot paintings with different palettes from his other spot paintings or from something else. So there you have it. Generative Hirst Spot Paintings.

For nerds only

My original idea was to generate a palette of unique colours from the original painting. Because of the way I sampled them, each spot is represented once in the palette. This means the same colour as used by the artist is represented as several very similar but nonidentical colours in the palette. My original plan was to find the euclidean distances between all spots in RGB colour space and to establish a distance cutoff to decide what is a unique colour.

That part was easy to write but what value to give for the cutoff was tricky. After some reading, it seems that other colour spaces are better suited for this task, e.g. converting RGB to a CIE colour space. For two reasons, I didn’t pursue this. First, quantixed coding is time-limited. Second. assuming that there is something to the composition of these spot paintings (and they are not a con trick) the frequency of spots must have artistic merit and so they should be left in the palette for sampling in the generated pictures. The representation of the palette in RGB colour space had an interesting pattern (shown in the GIF above).

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The post title comes from “Paintball’s Coming Home” by Half Man Half Biscuit from Voyage To The Bottom Of The Road. Spot paintings are kind of paintballs, but mostly because I love the title of this song.

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Scoop: some practical advice

So quantixed occasionally gets correspondence from other researchers asking for advice. A recent email came from someone who had been “scooped”. What should they do?

Before we get into this topic we have to define what we mean by being scooped.

In the most straightforward sense being scooped means that an article appeared online before you managed to get your article online.

You were working on something that someone else was also working on – maybe you knew about this or not and vice versa – but they got their work out before you did. They are the scooper and you are the scoopee.

There is another use of the term, primarily used in highly competitive fields, which define the act of scooping as the scooper have gained some unfair advantage to make the scoop. In the worst case, this can be done by receiving your article to review confidentially and then delaying your work while using your information to accelerate their own work (Ginsparg, 2016).

However it happens, the scoop can classified as an overscoop or an underscoop. An overscoop is where the scooper has much more data and a far more complete story. Maybe the scooper’s paper appears in high profile journal while the scoopee was planning on submitting to a less-selective journal.  Perhaps the scooper has the cell data, an animal model, the biochemical data and a crystal structure; while the scoopee had some nice data in cells and a bit of biochemistry. An underscoop is where a key observation that the scoopee was building into a full paper is partially revealed. The scoopee could have more data or better quality results and maybe the full mechanism, but the scooper’s paper gives away a key detail (Mole, 2004).

All of these definitions are different from the journalistic definition which simply means “the scoop” is the big story. What the science and journalistic term share is the belief that being second with a story is worthless. In science, being second and getting the details right is valuable and more weight should be given that it currently is. I think follow-up work is valued by the community, but it is fair to say that it is unlikely to receive the same billing and attention as the scooper’s paper.

How often does scooping actually happen?

To qualify as being scooped, you need to have a paper that you are preparing for publication when the other paper appears. If you are not at that point, someone else was just working on something similar and they’ve published a paper. They haven’t scooped you. This is easiest to take when you have just had an idea or have maybe done a few experiments and then you see a paper on the same thing. It must’ve been a good idea! The other paper has saved you some time! Great. Move on. The problem comes when you have invested a lot of time doing a whole bunch of work and then the other paper appears. This is very annoying, but to reiterate, you haven’t really been scooped if you weren’t actually at the point of preparing your work for publication.

As you might have gathered, I am not even sure scooping is a real thing. For sure the fear of being scooped is real. And there are instances of scooping happening. But most of the time the scoopee has not actually been scooped. And even then, the scoopee does not just abandon their work.

So what is the advice to someone who has discovered that they have been scooped?

Firstly, don’t panic! The scoopers paper is not going to go away and you have to deal with the fact you now have the follow up paper. It can be hard to change your mindset, but you must rewrite your paper to take their work into account. Going into denial mode and trying to publish your work as though the other paper doesn’t exist is a huge mistake.

Second, read their work carefully. I doubt that the scooper has left you with no room for manoeuvre. Even in the case of the overscoop, you probably still have something that the other paper doesn’t have that you can still salvage. There’s bound to be some details on which your work does not agree and this can feature in your paper. If it’s an underscoop, you have even less to worry about. There will be a way forward – you just need to identify it and move on.

The main message is that “being scooped” is not the end. You just need to figure out your way forward.

How do I stop it from happening to me?

Be original! It’s a truism that if you are working on something interesting, it’s likely that someone else is too. And if you work in a highly competitive area, there might be many groups working on the same thing and it is more likely that you will be scooped. Some questions are obvious next steps and it might be worth thinking twice about pursuing them. This is especially true if you come up with an idea based on a paper you’ve read. Work takes so long to appear that the lab who published that paper is likely far ahead of you.

Having your own niche gives the best protection. If you have carved out your own question you probably have the lead and will be associated with work in this area anyway. Other labs will back off. If you have a highly specialised method, again you can contribute in ways that others can’t and so your chances of being scooped decrease.

Have a backup plan. Do you have a side project which you can switch to if too much novelty is taken away from your main project? You can insulate yourself from scoop damage by not working on projects that are all-or-nothing. Horror stories about scooping in structural biology (which is all about “the big reveal”) are commonplace. Investing energy in alternative approaches or new assays as well as getting a structure might help here.

If you find out about competition, maybe from a poster or a talk at a meeting, you need to evaluate whether it is worth carrying on. If you can, talk to the other lab. Most labs do not want to compete and would prefer to collaborate or at least co-ordinate submission of manuscripts.

Use preprints! If you deposit your work on a preprint server, you get a DOI and a date stamp. You can prove that your work existed on that date and in what form. This is ultimate protection against being scooped. If someone else’s work appears online before you do this, then as I said above, you haven’t really been scooped. If work appears and you already have a DOI, well, then you haven’t been scooped either. Some journals see things this way. For example, EMBO J have a scoop protection policy that states that the preprint deposition timestamp is the date at which priority is assessed.

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The post title is taken from “Scoop” by The Auctioneers. I have this track on an extended C86 3-Disc set.

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Measured Steps: Garmin step adjustment algorithm

I recently got a new GPS running watch, a Garmin Fēnix 5. As well as tracking runs, cycling and swimming, it does “activity tracking” – number of steps taken in a day, sleep, and so on. The step goals are set to move automatically and I wondered how it worked. With a quick number crunch, the algorithm revealed itself. Read on if you are interested how it works.

Step screen on the Garmin Fēnix 5

The watch started out with a step target of 7500 steps in one day. I missed this by 2801 and the target got reduced by 560 to 6940 for the next day. That day I managed 12480, i.e. 5540 over the target. So the target went up by 560 to 7500. With me so far? Good. So next I went over the target and it went up again (but this time by 590 steps). I missed that target by a lot and the target was reduced by 530 steps. This told me that I’d need to collect a bit more data to figure out how the goal is set. Here are the first few days to help you see the problem.

Actual steps Goal Deficit/Surplus Adjustment for Tomorrow
4699 7500 -2801 -560
12480 6940 5540 560
10417 7500 2917 590
2726 8090 -5364 -530
6451 7560 -1109 -220
8843 7340 1503 150
8984 7490 1494 300
9216 7790 1426 290

The data is available for download as a csv via the Garmin Connect website. After waiting to accumulate some more data, I plotted out the adjustment vs step deficit/surplus. The pattern was pretty clear.

There are two slopes here that pass through the origin. It doesn’t matter what the target was, the adjustment applied is scaled according to how close to the target I was, i.e. the step deficit or surplus. There was either a small (0.1) or large (0.2) scaling used to adjust the step target for the next day, but how did the watch decide which scale to use?

The answer was to look back at the previous day’s activity as well as the current day.

So if today you exceeded the target and you also exceeded the target yesterday then you get a small scale increase. Likewise if you fell short today and yesterday, you get a small scale decrease. However, if you’ve exceeded today but fell short yesterday, your target goes up by the big scaling. Falling short after exceeding yesterday is rewarded with a big scale decrease. The actual size of the decrease depends on the deficit or surplus on that day. The above plot is coloured according to the four possibilities described here.

I guess there is a logic to this. The goal could quickly get unreachable if it increased by 20% on a run of two days exceeding the target, and conversely, too easy if the decreases went down rapidly with consecutive inactivity. It’s only when there’s been a swing in activity that the goal should get moved by the large scaling. Otherwise, 10% in the direction of attainment is fine.

I have no idea if this is the algorithm used across all of Garmin’s watches or if other watch manufacturer’s use different target-setting algorithms.

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The post title comes from “Measured Steps” by Edsel from their Techniques of Speed Hypnosis album.

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Esoteric Circle

Many projects in the lab involve quantifying circular objects. Microtubules, vesicles and so on are approximately circular in cross section. This quick post is about how to find the diameter of these objects using a computer.

So how do you measure the diameter of an object that is approximately circular? Well, if it was circular you would measure the distance from one edge to the other, crossing the centre of the object. It doesn’t matter along which axis you do this. However, since these objects are only approximately circular, it matters along which axis you measure. There are a couple of approaches that can be used to solve this problem.

Principal component analysis

The object is a collection of points* and we can find the eigenvectors and eigenvalues of these points using principal component analysis. This was discussed previously here. The 1st eigenvector points along the direction of greatest variance and the 2nd eigenvector is normal to the first. The order of eigenvectors is determined by their eigenvalues. We use these to rotate the coordinate set and offset to the origin.

Now the major axis of the object is aligned to the x-axis at y=0 and the minor axis is aligned with the y-axis at x=0 (compare the plot on the right with the one on the left, where the profiles are in their original orientation – offset to zero). We can then find the absolute values of the axis crossing points and when added together these represent the major axis and minor axis of the object. In Igor, this is done using a oneliner to retrieve a rotated set of coords as the wave M_R.

PCA/ALL/SEVC/SRMT/SCMT xCoord,yCoord

To find the crossing points, I use Igor’s interpolation-based level crossing functions. For example, storing the aggregated diameter in a variable called len.

FindLevel/Q/EDGE=1/P m1c0, 0
len = abs(m1c1(V_LevelX))
FindLevel/Q/EDGE=2/P m1c0, 0
len += abs(m1c1(V_LevelX))

This is just to find one axis (where m1c0 and m1c1 are the 1st and 2nd columns of a 2-column wave m1) and so you can see it is a bit cumbersome.

Anyway, I was quite happy with this solution. It is unbiased and also tells us how approximately circular the object is (because the major and minor axes tell us the aspect ratio or ellipticity of the object). I used it in Figure 2 of this paper to show the sizes of the coated vesicles. However, in another project we wanted to state what the diameter of a vesicle was. Not two numbers, just one. How do we do that? We could take the average of the major and minor axes, but maybe there’s an easier way.

Polar coordinates

The distance from the centre to every point on the edge of the object can be found easily by converting the xy coordinates to polar coordinates. To do this, we first find the centre of the object. This is the centroid \((\bar{x},\bar{y})\) represented by

\(\bar{x} = \frac{1}{n}\sum_{i=1}^{n} x_{i} \) and \(\bar{y} = \frac{1}{n}\sum_{i=1}^{n} y_{i} \)

for n points and subtract this centroid from all points to arrange the object around the origin. Now, since the xy coords are represented in polar system by

\(x_{i} = r_{i}\cos(\phi) \) and \(y_{i} = r_{i}\sin(\phi) \)

we can find r, the radial distance, using

\(r_{i} = \sqrt{x_{i}^{2} + y_{i}^{2}}\)

With those values we can then find the average radial distance and report that.

There’s something slightly circular (pardon the pun) about this method because all we are doing is minimising the distance to a central point initially and then measuring the average distance to this minimised point in the latter step. It is much faster than the PCA approach and would be insensitive to changes in point density around the object. The two methods would probably diverge for noisy images. Again in Igor this is simple:

Make/O/N=(dimsize(m1,0)-1)/FREE rW

rW[] = sqrt(m1[p][0]^2 + m1[p][1]^2)

len = 2 * mean(rW)
Here again, m1 is the 2-column wave of coords and the diameter of the object is stored in len.

How does this compare with the method above? The answer is kind of obvious, but it is equidistant between the major and minor axes. Major axis is shown in red and minor axis shown in blue compared with the mean radial distance method (plotted on the y-axis). In places there is nearly a 10 nm difference which is considerable for objects which are between 20 and 35 nm in diameter. How close is it to the average of the major and minor axis? Those points are in black and they are very close but not exactly on y=x.

So for simple, approximately circular objects with low noise, the ridiculously simple polar method gives us a single estimate of the diameter of the object and this is much faster than the more complex methods above. For more complicated shapes and noisy images, my feeling is that the PCA approach would be more robust. The two methods actually tell us two subtly different things about the shapes.

Why don’t you just measure them by hand?

In case there is anyone out there wondering why a computer is used for this rather than a human wielding the line tool in ImageJ… there are two good reasons.

  1. There are just too many! Each image has tens of profiles and we have hundreds of images from several experiments.
  2. How would you measure the profile manually? This approach shows two unbiased methods that don’t rely on a human to draw any line across the object.

* = I am assuming that the point set is already created.

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The post title is taken from “Esoteric Circle” by Jan Garbarek from the LP of the same name released in 1969. The title fits well since this post is definitely esoteric. But maybe someone out there is interested!

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Inspiration Information: some book recommendations for kids

As with children’s toys and clothes, books aimed at children tend to be targeted in a gender-stereotyped way. This is a bit depressing. While books about princesses can be inspirational to young girls – if the protagonist decides to give it all up and have a career as a medic instead (the plot to Zog by Julia Donaldson) – mostly they are not. How about injecting some real inspiration into reading matter for kids?

Here are a few recommendations. This is not a survey of the entire market, just a few books that I’ve come across that have been road-tested and received a mini-thumbs up from little people I know.

Little People Big Dreams: Marie Curie by Isabel Sanchez Vegara & Frau Isa

This is a wonderfully illustrated book that tells the story of Marie Curie. From a young girl growing up in Poland, overcoming gender restrictions to go and study in France and subsequently winning two Nobel Prizes and being a war hero! The front part of the book is written in simple language that kids can read while the last few pages are (I guess) for an adult to read aloud to the child, or for older children to read for themselves.

This book is part of a series which features inspirational women: Ada Lovelace, Rosa Parks, Emmeline Pankhurst, Amelia Earhart. What is nice is that the series also has books on women from creative fields Coco Chanel, Audrey Hepburn, Frida Kahlo, Ella Fitzgerald. Often non-fiction books for kids are centred on science/tech/human rights which is great but, let’s face it, not all kids will engage with these topics. The bigger message here is to show young people that little people with big dreams can change the world.

Ada Twist, Scientist by Andrea Beaty & David Roberts

A story about a young scientist who keeps on asking questions. The moral of the story is that there is nothing wrong with asking “why?”. The artwork is gorgeous and there are plenty of things to spot and look at on each page. The mystery of the book is not exactly solved either so there’s fun to be had discussing this as well as reading the book straight. Ada Marie Twist is named after Ada Lovelace and Marie Curie, two female giants of science.

This book is highly recommended. It’s fun and crammed full with positivity.

Rosie Revere, Engineer by Andrea Beaty & David Roberts

By the same author and illustrator, ‘Rosie Revere…’ tells the story of a young inventor. She overcomes ridicule when she is taken under the wing of her great aunt who is an inspirational engineer. Her great aunt Rose is I think supposed to be Rosie the Riveter, be-headscarfed feminist icon from WWII. A wonderful touch.

Rosie is a classmate of Ada Twist (see above) and there is another book featuring a young (male) architect which we have not yet road-tested. Rather than recruitment propaganda for Engineering degrees, the broader message of ‘Rosie Revere…’ is that persevering with your ideas and interests is a good thing, i.e. never give up.

Good Night Stories for Rebel Girls by Elena Favilli & Francesca Cavallo
A wonderful book that gives brief biographies of inspiring women. Each two page spread has some text and an illustration of the rebel girl to inspire young readers. The book has a This book belongs to… page at the beginning, but in a move of pure genius, the book has two final pages for the owner of the book to write their own story. Just like the women featured in the book, the owner to the book can have their own one page story and draw their own self-portrait.
This book is highly recommended.
EDIT: this book was added to the list on 2018-02-26

Who was Charles Darwin? by Deborah Hopkinson & Nancy Harrison

This is a non-fiction book covering Darwin’s life from school days through the Beagle adventures and on to old age. It’s a book for children although compared to the books above, this is quite a dry biography with a few black-and-white illustrations. This says more about how well the books above are illustrated rather than anything particularly bad about “Who Was Charles Darwin?”. Making historical or biographical texts appealing to kids is a tough gig.

The text is somewhat inspirational – Darwin’s great achievements were made despite personal problems – but there is a disconnect between the life of a historical figure like Darwin and the children of today.

For older people

Quantum Mechanics by Jim Al-Khalili

Aimed at older children and adults, this book explains the basics behind the big concept of “Quantum Mechanics”. These Ladybird Expert books have a retro appeal, being similar to the original Ladybird books published over forty years ago. Jim Al-Khalili is a great science communicator and any young people (or adults) who have engaged with his TV work will enjoy this short format book.

Evolution by Steve Jones

This is another book in the Ladybird Expert series (there is one further book, on “Climate Change”). The brief here is the same: a short format explainer of a big concept, this time “Evolution”. The target audience is the same. It is too dry for young children but perfect for teens and for adults. Steve Jones is an engaging writer and this book doesn’t disappoint, although the format is limited to one-page large text vignettes on evolution with an illustration on the facing page.

It’s a gateway to further reading on the topic and there’s a nice list of resources at the end.

 

 

Computing for Kids

After posting this, I realised that we have lots of other children’s science and tech books that I could have included. The best of the rest is this “lift-the-flap” book on Computers and Coding published by Usborne. It’s a great book that introduces computing concepts in a fun gender-free way. It can inspire kids to get into programming perhaps making a step up from Scratch Jr or some other platform that they use at school.

I haven’t included any links to buy these books. Of course, they’re only a google search away. If you like the sound of any, why not drop in to your local independent bookshop and support them by buying a copy there.

Any other recommendations for inspirational reading for kids? Leave a comment below.

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The post title comes from the title track of the “Inspiration Information” LP by Shuggie Otis. The version I have is the re-release with  ‘Strawberry Letter 23’ on it from ‘Freedom Flight’ – probably his best known track – as well as a host of other great tunes. Highly underrated, check it out. There’s another recommendation for you.

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In a Word: LaTeX to Word and vice versa

Here’s a quick tech tip. We’ve been writing papers in TeX recently, using Overleaf as a way to write collaboratively. This works great but sometimes, a Word file is required by the publisher. So how do you convert from one to the other quickly and with the least hassle?

If you Google this question (as I did), you will find a number of suggestions which vary in the amount of effort required. Methods include latex2rtf or pandoc. Here’s what worked for me:

  • Exporting the TeX file as PDF from Overleaf
  • Opening it in Microsoft Word
  • That was it!

OK, that wasn’t quite it. It did not work at all on a Mac. I had to use a Windows machine running Word. The formatting was maintained and the pictures imported OK. Note that this was a short article with three figures and hardly any special notation (it’s possible this doesn’t work as well on more complex documents). A couple of corrections were needed: hyphenation at the end of the line was deleted during the import which borked actual hyphenated words which happened to span two lines; and the units generated by siunitx were missing a space between the number and unit. Otherwise it was pretty straightforward. So straightforward that I thought I’d write a quick post in case it helps other people.

What about going the other way?

Again, on Windows I used Apache OpenOffice to open my Word document and save it as an otd file. I then used the writer2latex filter to make a .tex file with all the embedded images saved in a folder. These could then be uploaded to Overleaf. With a bit of formatting work, I was up-and-running.

I had heard that many publishers, even those that say that they accept manuscripts as TeX files actually require a Word document for typesetting. This is because, I guess, they have workflows set up to make the publisher version which must start with a Word document and nothing else. What’s more worrying is that in these cases, if you don’t supply one, they will convert it for you before putting into the workflow. It’s probably better to do this yourself and check the conversion to reduce errors at the proof stage.

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The post title is taken from “In A Word” the compilation album by Nottingham noise-rockers Fudge Tunnel.

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Some Things Last A Long Time II

Back in 2014, I posted an analysis of the time my lab takes to publish our work. This post is very popular. Probably because it looks at the total time it takes us to publish our work. It was time for an update. Here is the latest version.

The colours have changed a bit but again the graphic shows that the journey to publication in four “eras”:

  1. 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.
  2. Submission at the final journal (starting at time 0). Again, the lime-coloured periods are when the manuscript is with the journal and the green ones, when it is with us (being revised).
  3. Acceptance! This is where the lime bar stops. The manuscript is then readied for publication (blank area).
  4. Published online. A red period that ends with final publication in print.

Since 2013 we have been preprinting our work, which means that the manuscript is available while it is under review. This procedure means that the journey to publication only delays the work appearing in the journal and not its use by other scientists. If you want to find out more about preprints in biology check out ASAPbio.org or my posts here and here.

The mean time from first submission to the paper appearing online in the journal is 226 days (median 210). Which is shorter than the last time I did this analysis (250 days). Sadly though we managed to set a new record for longest time to publication with 450 days! This is sad for the first author concerned who worked hard (259 days in total) revising the paper when she could have been doing other stuff. It is not all bad though. That paper was put up on bioRxiv the day we first submitted it so the pain is offset somewhat.

What is not shown in the graphic is the other papers that are still making their way through the process. These manuscripts will change the stats again likely pushing up the times. As I said in the last post, I think the delays we experience are pretty typical for our field and if anything, my group are quite quick to publish.

If you’d like to read more about publication lag times see here.

Thanks to Jessica Polka for nudging me to update this post.

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The post title comes again from Daniel Johnston’s track “Some Things Last A Long Time” from his “1990” LP.

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Methods papers for MD997

I am now running a new module for masters students, MD997. The aim is to introduce the class to a range of advanced research methods and to get them to think about how to formulate their own research question(s).

The module is built around a paper which is allocated in the first session. I had to come up with a list of methods-type papers, which I am posting below. There are 16 students and I picked 23 papers. I aimed to cover their interests, which are biological but with some chemistry, physics and programming thrown in. The papers are a bit imaging-biased but I tried to get some ‘omics and neuro in there. There were some preprints on the list to make sure I covered the latest stuff.

The students picked their top 3 papers and we managed to assign them without too much trouble. Every paper got at least one vote. Some papers were in high demand. Fitzpatrick et al. on cryoEM of Alzheimer’s samples and the organoid paper from Lancaster et al. had by far the most votes.

The students present this paper to the class and also use it to formulate their own research proposal. Which one would you pick?

  1. Booth, D.G. et al. (2016) 3D-CLEM Reveals that a Major Portion of Mitotic Chromosomes Is Not Chromatin Mol Cell 64, 790-802. http://dx.doi.org/10.1016/j.molcel.2016.10.009
  2. Chai, H. et al. (2017) Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence Neuron 95, 531-549 e9. http://dx.doi.org/10.1016/j.neuron.2017.06.029
  3. Chang, J.B. et al. (2017) Iterative expansion microscopy Nat Methods 14, 593-599. http://dx.doi.org/10.1038/nmeth.4261
  4. Chen, B.C. et al. (2014) Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution Science 346, 1257998. http://dx.doi.org/10.1126/science.1257998
  5. Chung, K. & Deisseroth, K. (2013) CLARITY for mapping the nervous system Nat Methods 10, 508-13. http://dx.doi.org/10.1038/nmeth.2481
  6. Eichler, K. et al. (2017) The Complete Connectome Of A Learning And Memory Center In An Insect Brain bioRxiv. http://dx.doi.org/10.1101/141762
  7. Fitzpatrick, A.W.P. et al. (2017) Cryo-EM structures of tau filaments from Alzheimer’s disease Nature 547, 185-190. http://dx.doi.org/10.1038/nature23002
  8. Habib, N. et al. (2017) Massively parallel single-nucleus RNA-seq with DroNc-seq Nat Methods 14, 955-958. http://dx.doi.org/10.1038/nmeth.4407
  9. Hardman, G. et al. (2017) Extensive non-canonical phosphorylation in human cells revealed using strong-anion exchange-mediated phosphoproteomics bioRxiv. http://dx.doi.org/10.1101/202820
  10. Herzik, M.A., Jr. et al. (2017) Achieving better-than-3-A resolution by single-particle cryo-EM at 200 keV Nat Methods. http://dx.doi.org/10.1038/nmeth.4461
  11. Jacquemet, G. et al. (2017) FiloQuant reveals increased filopodia density during breast cancer progression J Cell Biol 216, 3387-3403. http://dx.doi.org/10.1083/jcb.201704045
  12. Jungmann, R. et al. (2014) Multiplexed 3D cellular super-resolution imaging with DNA-PAINT and Exchange-PAINT Nat Methods 11, 313-8. http://dx.doi.org/10.1038/nmeth.2835
  13. Kim, D.I. et al. (2016) An improved smaller biotin ligase for BioID proximity labeling Mol Biol Cell 27, 1188-96. http://dx.doi.org/10.1091/mbc.E15-12-0844
  14. Lancaster, M.A. et al. (2013) Cerebral organoids model human brain development and microcephaly Nature 501, 373-9. http://dx.doi.org/10.1038/nature12517
  15. Madisen, L. et al. (2012) A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing Nat Neurosci 15, 793-802. http://dx.doi.org/10.1038/nn.3078
  16. Penn, A.C. et al. (2017) Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors Nature 549, 384-388. http://dx.doi.org/10.1038/nature23658
  17. Qin, P. et al. (2017) Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9 Nat Commun 8, 14725. http://dx.doi.org/10.1038/ncomms14725
  18. Quick, J. et al. (2016) Real-time, portable genome sequencing for Ebola surveillance Nature 530, 228-232. http://dx.doi.org/10.1038/nature16996
  19. Ries, J. et al. (2012) A simple, versatile method for GFP-based super-resolution microscopy via nanobodies Nat Methods 9, 582-4. http://dx.doi.org/10.1038/nmeth.1991
  20. Rogerson, D.T. et al. (2015) Efficient genetic encoding of phosphoserine and its nonhydrolyzable analog Nat Chem Biol 11, 496-503. http://dx.doi.org/10.1038/nchembio.1823
  21. Russell, M.R. et al. (2017) 3D correlative light and electron microscopy of cultured cells using serial blockface scanning electron microscopy J Cell Sci 130, 278-291. http://dx.doi.org/10.1242/jcs.188433
  22. Strickland, D. et al. (2012) TULIPs: tunable, light-controlled interacting protein tags for cell biology Nat Methods 9, 379-84. http://dx.doi.org/10.1038/nmeth.1904
  23. Yang, J. et al. (2015) The I-TASSER Suite: protein structure and function prediction Nat Methods 12, 7-8. http://dx.doi.org/10.1038/nmeth.3213

If you are going to do a similar exercise, Twitter is invaluable for suggestions for papers. None of the students complained that they couldn’t find three papers which matched their interests. I set up a slide carousel in Powerpoint with the front page of each paper together with some key words to tell the class quickly what the paper was about. I gave them some discussion time and then collated their choices on the board. Assigning the papers was quite straightforward, trying to honour the first choices as far as possible. Having an excess of papers prevented too much horse trading for the papers that multiple people had picked.

Hopefully you find this list useful. I was inspired by Raphaël posting his own list here.

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