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Five selfish reasons to work reproducibly | Genome Biology | Full Text

 Source: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-015-0850-7

Five selfish reasons to work reproducibly

Genome Biology201516:274
DOI: 10.1186/s13059-015-0850-7
Published: 8 December 2015

Abstract

And
so, my fellow scientists: ask not what you can do for reproducibility;
ask what reproducibility can do for you! Here, I present five reasons
why working reproducibly pays off in the long run and is in the
self-interest of every ambitious, career-oriented scientist.

Keywords

Reproducibility
Scientific career

A complex equation on the left
half of a black board, an even more complex equation on the right half. A
short sentence links the two equations: “Here a miracle occurs”. Two
mathematicians in deep thought. “I think you should be more explicit in
this step”, says one to the other.
This is exactly how it seems when
you try to figure out how authors got from a large and complex data set
to a dense paper with lots of busy figures. Without access to the data
and the analysis code, a miracle occurred. And there should be no
miracles in science.
Working transparently and
reproducibly has a lot to do with empathy: put yourself into the shoes
of one of your collaboration partners and ask yourself, would that
person be able to access my data and make sense of my analyses. Learning
the tools of the trade (Box 1) will require commitment and a massive
investment of your time and energy. A priori it is not clear why the
benefits of working reproducibly outweigh its costs.
Here are some reasons: because
reproducibility is the right thing to do! Because it is the foundation
of science! Because the world would be a better place if everyone worked
transparently and reproducibly! You know how that reasoning sounds to
me? Just like yaddah, yaddah, yaddah …
It’s not that I think these
reasons are wrong. It’s just that I am not much of an idealist; I don’t
care how science should be. I am a realist; I try to do my best given
how science actually is. And, whether you like it or not, science is all
about more publications, more impact factor, more money and more
career. More, more, more… so how does working reproducibly help me
achieve more as a scientist.

Reproducibility: what’s in it for me?

In
this article, I present five reasons why working reproducibly pays off
in the long run and is in the self-interest of every ambitious,
career-oriented scientist.

Reason number 1: reproducibility helps to avoid disaster

“How bright promise in cancer testing fell apart” titled a The New York Times article published in summer 2011 [1]
highlighting the work of Keith Baggerly and Kevin Coombes, two
biostatisticians at M.D. Anderson Cancer Center. Baggerly and Coombes
had exposed lethal data analysis problems in a series of high-impact
papers by breast cancer researchers from Duke University [2].
The
issues discovered by Baggerly and Coombes could have easily been
spotted by any co-author before submitting the paper. The data sets are
not huge and can easily be spot-checked on a standard laptop. You do not
have to be a statistics wizard to realize that patient numbers differ,
labels got swapped or samples appear multiple times with conflicting
annotations in the same data set. Why did no one notice these issues
before it was too late? Because the data and analysis were not
transparent and required forensic bioinformatics to untangle [2].
For
me, this example provides a powerful motivation to be more transparent
and reproducible in my own work. Even smaller disasters can be
embarrassing. Here is an example from my own research. Our experimental
collaboration partners were validating a pathway model that we had
generated computationally. When writing the paper, however, we hit a
crucial roadblock: no matter how hard we tried, we could not reproduce
our initial pathway model. Maybe the data had changed, maybe the code
was different, or maybe we just couldn’t remember the parameter settings
of our method correctly. Had we published this result, we would not
have been able to demonstrate how the validated hypothesis was generated
from the initial data. We would have published a miracle.
This
experience showed me two things. First of all, a project is more than a
beautiful result. You need to record in detail how you got there. And
second, starting to work reproducibly early on will save you time later.
We wasted years of our and our collaborators’ time by not being able to
reproduce our own results. All of this could have been avoided by
keeping better track of how the data and analyses evolved over time.

Reason number 2: reproducibility makes it easier to write papers

Transparency
in your analysis makes writing papers much easier. For example, in a
dynamic document (Box 1) all results automatically update when the data
are changed. You can be confident your numbers, figures and tables are
up-to-date. Additionally, transparent analyses are more engaging, more
eyes can look over them and it is much easier to spot mistakes.
Here is another example from my own work. In a different project [3],
a collaborating clinician and I were discussing why some survival
results in a multi-centre study did not come out as expected. Because
all the data and analysis code were available to us in an easy-to-read
file, we could explore the question ourselves. By simply generating a
table of the variable describing tumor stage, we were able to spot the
problem: what we expected to see were the stage numbers 1–4, what we saw
were entries like ‘XXX’, ‘Fred’ and ‘999’. The people who had given us
the data had apparently done a poor job in curating it. Looking into the
data ourselves was much quicker and more engaging than going to the
postdoc working on the project and saying, ‘Figure this out for us’. My
collaborator and I are much too busy to spend too much time on low-level
data cleaning, and without the well documented analysis we would not
have been able to contribute; but because we had very transparent data
and code, it cost us just five minutes to spot a mistake.

Reason number 3: reproducibility helps reviewers see it your way

Most
of us like to moan about peer review. One of the complaints I hear most
often is: the reviewers didn’t even read the paper and had no idea what
we were really doing.
This starkly contrasts with my experience during the review process of a recent paper [4],
for which we had made the data and well-documented code easily
accessible to the reviewers. One of the reviewers proposed a slight
change to some analyses, and because he had access to the complete
analysis, he could directly try out his ideas on our data and see how
the results changed. The reviewer was completely on board, the only
thing left to discuss was the best way to analyze the data. Exactly how a
constructive review should be. And it would have been impossible
without a transparent and reproducible presentation of our analyses.

Reason number 4: reproducibility enables continuity of your work

I
would be surprised if you hadn’t heard the following remarks before,
maybe you have even said them yourself: “I am so busy, I can’t remember
all the details of all my projects” or “I did this analysis 6 months
ago. Of course I can’t remember all the details after such a long time”
or “My principle investigator (PI) said I should continue the project of
a previous postdoc, but that postdoc is long gone and hasn’t saved any
scripts or data”.
Think
about it, all of these issues can be solved by documenting data and
code well and by making them easily accessible. This point is
particularly important for PIs who work on challenging long-term
projects. How can you ensure the continuity of work in your lab if
progress is not documented reproducibly? In my own group, I don’t even
discuss results with students if they are not documented well. No proof
of reproducibility, no result!

Reason number 5: reproducibility helps to build your reputation

For several papers, we have made our data, code and analyses available as an Experiment Package on Bioconductor [5].
When I came up for tenure, I cited all of these packages as research
output of my lab. Generally, making your analyses available in this way
will help you to build a reputation for being an honest and careful
researcher. Should there ever be a problem with one of your papers, you
will be in a very good position to defend yourself and to show that you
reported everything in good faith.
The recent paper published in Science “Scientific standards. Promoting an open research culture” [6]
summarizes eight standards and three levels of reproducibility
guidelines. Using tools such as R and knitR (Box 1) will make it likely
that you comply easily with the highest-level guideline — and again,
that is good for your reputation.

What’s holding you back?

Have
I convinced you? Maybe not. Here is a collection of responses I
sometimes get to my insistence on reproducible research (as well as my
answers to them):
It’s only the result that matters!” You are wrong.
I’d rather do real science than tidy up my data”. If you don’t work reproducibly, you are not doing science at all [7].
Mind your own business! I document my data the way I want!” Yes, please do! There are many ways to work reproducibly [8] and you can pick whatever suits you best.
Excel works just fine. I don’t need any fancy R or Python or whatever.
The tool you mention might work well if lots of manual curation is
needed, but as soon as you do data analysis, less clicking and more
scripting are the way to go. Imagine you have to do a simple analysis
such as a regression plot 5 times (10 times, 20 times) and compare doing
it by hand 5 times (10 times, 20 times) to writing a simple loop to do
it for you. Now imagine having to do it again 3 weeks later because the
data have slightly changed. R and Python are clearly the way to go.
Reproducibility
sounds alright, but my code and data are spread over so many hard
drives and directories that it would just be too much work to collect
them all in one place
. Just think about what you just said. Your lack of organization puts you and your project in grave danger.
We can always sort out the code and data after submission.
My pathway example above shows the danger of this strategy. Also,
preparing a manuscript for submission can take a long time and you might
not even remember all the details of your analysis by the time you
submit your results.
My field is very competitive and I can’t risk wasting time. And that is exactly why you should start working reproducibly early on, so you don’t waste time in the long run.

When do you need to worry about reproducibility?

Let’s
assume that I have convinced you that reproducibility and transparency
are in your own best interest. Then what is the best time to worry about
it?
Long
answer: before you start the project, because you might have to learn
tools like R or git. While you do the analysis, because if you wait too
long you might lose a lot of time trying to remember what you did two
months ago. When you write the paper, because you want your numbers,
tables and figures to be up to date. When you co-author a paper, because
you want to make sure that the analyses presented in a paper with your
name on are sound. When you review a paper, because you can’t judge the
results if you don’t know how the authors got there.
Short answer: Always!

Achieving a culture of reproducibility

Who
are reproducibility and transparency important for? Obviously, students
and postdocs play a major part in reproducible work, because more often
than not they are the people who actually do the work. My advice is:
learn the tools of reproducibility (Box 1) as quickly as possible and
use them in every project. You will get many benefits out of these
efforts: you will make fewer mistakes and more easily correct those that
you do make; you will be more efficient and in the long run progress
much faster; and if you think your supervisor is too hands-off, making
your analyses more accessible is a good strategy to help them be more
engaged.
PIs,
group leaders, professors, team leaders — it is up to you to build a
‘culture of reproducibility’ on top of the technical foundations your
students and postdocs have laid. In my own lab, I have made
reproducibility a key point in a document that I hand out to new
starters [9].
A simple strategy to show your support is to ask for documentation of
analysis every time a team member shows you their result. You don’t have
to go into the details; a quick look will tell you how well it is done.
What has really improved reproducibility in my own lab is to require
that, before paper submission, a team member not involved in the project
tries to independently run the analyses and reproduce our results.
If
you fail to create a culture of reproducibility in your lab, you will
miss out on the large scientific pay-offs that reproducibility offers in
the long run.
Science
is becoming more transparent and reproducible every single day. You can
be a leader in this process! A cutting-edge trend-setter! Come on, I
know you want it too.

Twitter and blog

Follow Florian on Twitter @markowetzlab and on his blog http://​scientificbsides​.​wordpress.​com

Box 1

At
the lowest level, working reproducibly just means avoiding beginners’
mistakes. Keep your project organized, name your files and directories
in some informative way, store your data and code at a single backed-up
location. Don’t spread your data over different servers, laptops and
hard drives.
To achieve the next levels of reproducibility, you need to learn some tools of computational reproducibility [8].
In general, reproducibility is improved when there is less clicking and
pasting and more scripting and coding. For example, do your analysis in
R (https://​www.​r-project.​org/​) or Python (https://​www.​python.​org/​) and document your analysis using knitR (http://​yihui.​name/​knitr/​) or IPython notebooks (http://​ipython.​org/​).
These tools help you to merge descriptive text with analysis code into
dynamic documents that can be automatically updated every time the data
or code change.
As a next step, learn how to use a version-control system like git (https://​git-scm.​com/​) on a collaborative platform such as GitHub (https://​github.​com/​). Finally, if you want to become a pro, learn to use docker (http://​www.​docker.​com/​), which will make your analysis self-contained and easily transportable to different systems.

Declarations

Acknowledgements

I
developed the selfish approach to reproducibility for a Postdoc
Masterclass on Reproducibility that I taught at the Gurdon Institute in
Cambridge together with Gordon Brown (CRUK Cambridge Institute) and
Stephen J. Eglen (DAMTP Cambridge). I thank them for their input. All
materials for this class are available from GitHub at https://​github.​com/​bioinformatics-core-shared-training/​rep-research-masterclass and my talk is documented on my blog at https://​scientificbsides​.​wordpress.​com/​2015/​07/​15/​five-selfish-reasons-for-working-reproducibly/​.

Funding

I would like to acknowledge
the support of The University of Cambridge, Cancer Research UK (CRUK)
and Hutchison Whampoa Limited. Parts of this work were funded by CRUK
core grant C14303/A17197.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​),
which permits unrestricted use, distribution, and reproduction in any
medium, provided you give appropriate credit to the original author(s)
and the source, provide a link to the Creative Commons license, and
indicate if changes were made. The Creative Commons Public Domain
Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.

References

  1. Kolata G. How bright promise in cancer testing fell apart. The New York Times. 2011. http://​www.​nytimes.​com/​2011/​07/​08/​health/​research/​08genes.​html?​_​r=​0.
  2. Baggerly
    KA, Coombes KR. Deriving chemosensitivity from cell lines: forensic
    bioinformatics and reproducible research in high-throughput biology. Ann
    Appl Stat. 2009;3:1309–34.View Article
  3. Martins
    FC, Santiago I, Trinh A, Xian J, Guo A, Sayal K, et al. Combined image
    and genomic analysis of high-grade serous ovarian cancer reveals PTEN
    loss as a common driver event and prognostic classifier. Genome Biol.
    2014;15:526.PubMed CentralView ArticlePubMed
  4. Schwarz
    RF, Ng CKY, Cooke SL, Newman S, Temple J, Piskorz AM, et al. Spatial
    and temporal heterogeneity in high-grade serous ovarian cancer: a
    phylogenetic analysis. PLoS Med. 2015;12:1001789.View Article
  5. Castro
    MAA, Fletcher M, Markowetz F, Meyer K. Gene expression data from breast
    cancer cells under FGFR2 signalling perturbation. BioConductor
    Experimental Package. http://​bioconductor.​org/​packages/​release/​data/​experiment/​html/​Fletcher2013a.​html. Accessed 27 Nov 2015.
  6. Nosek
    BA, Alter G, Banks GC, Borsboom D, Bowman SD, Breckler SJ, et al.
    Scientific standards. Promoting an open research culture. Science.
    2015;348:1422–5.PubMed CentralView ArticlePubMed
  7. Watson M. When will’open science’ become simply’science’? Genome Biol. 2015;16:101.PubMed CentralView ArticlePubMed
  8. Piccolo SR, Lee AB, Frampton MB. Tools and techniques for computational reproducibility. 2015. http://​biorxiv.​org/​content/​early/​2015/​07/​17/​022707. Accessed 27 Nov 2015.
  9. Markowetz F. You are not working for me; I am working with you. PLoS Comput Biol. 2015;11:1004387.View Article

Copyright

© Markowetz. 2015


Five selfish reasons to work reproducibly | Genome Biology | Full Text

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