Four reasons I won't use your sequence analysis pipeline

(and some related thoughts on reproducibility in computational science)

In a recent news article on the "data deluge" in biology, I was quoted as saying "It's not at all clear what you do with that data. Doing a comprehensive analysis of it is essentially impossible at the moment." So, naturally, a company picked up on that. I received an e-mail saying, in part, "...we can provide solutions to solve all of your NGS analysis problems."

I do wonder a bit that they saw me cited as a "bioinformatics specialist" and then made the leap to assume that I was incompetent at providing my own solutions, but then again I do the same thing to others, so I guess I shouldn't complain. And the problems I'm talking about are, literally, unsolved research problems -- which leaves me a bit skeptical that a company I've never heard of will have a solution. (I offered to send them our 500 GB soil metagenome data set. No response yet.) But my gut reaction was actually even more visceral: it was "hell, no!" There's no way I'd use someone else's pipeline!

So without further ado, here are four reasons why there is no way in hell I will use your sequence analysis pipeline.

  1. Your (claimed) methods aren't open, or open source.

It's Not Science to use methods that aren't well understood or open to examination. Period.

Think CLC Workbench here -- they have some kind of assembly software that they sell. What does it do? No one is quite sure, other than that it's de Bruijn graph based, and rumor has it that it's a greedy algorithm. It's way faster and lighterweight in memory usage than some other solutions. And when we compare its performance on metagenomes to other approaches, we get very different answers. So I don't trust it worth a damn. YMMV. But:

It's not Bad Science to use methods you don't understand in detail, as long as you have done sufficient controls. It's definitely Bad Science to use methods you can't understand in detail.

  1. I don't know what your pipeline actually does, either.

Do you record the analysis steps and parameters for each analysis, from start to end? Do you keep track of the versions of software and scripts? Is everything under version control in the first place? And can I look at it and verify what was run? Can it be included in the published record?

It's Bad Science to not have an audit trail of your computational pipeline. It astonishes me that professors who would fire grad students for not keeping a lab notebook don't seem to pay any attention to all of the stuff that goes on in their computer system.

3. The methods and source data you're applying are not well suited to the basic problem.

For example, you're using a manifestly broken transcriptome to do mRNAseq analysis; or you're using default mapping parameters to do gene expression analysis.

It's definitely Bad Science to use off-the-shelf methods without thinking critically about them. (Did you know that apparently the Bowtie folk don't use their own default parameters? Huh.)

  1. You don't understand the biological intricacies of my model system.

For example, you're proposing to apply a standard resequencing mapping pipeline to metagenomic samples with significant unknowns, or with a lot of strain variation; or you're proposing to assemble a highly polymorphic population with an off-the-shelf diploid genome assembly package.

Fo' sure it's Bad Science to do Bad Science.

---

The above four reasons describe my general aversion to all forms of data analysis done on MY data from MY biology. If you want to know why I have no intention of using IMG/M or MG-RAST, for example -- well, there it is. (I can get more specific, just let me know :).

Unfortunately, those of you who are paying attention may have noticed the corner I just backed myself into. NOBODY does Data Science to my standards -- not even myself! I'm a total hypocrite. Oops.

I don't even know of any software packages that keep effective audit trails, for example; I've been looking for a while. (Cue the next corporate e-mail offering me AuditTrail2000... on Windows... sigh) We're good with the "open source stuff" (point 1), and we're feeling our way towards point 3 and point 4 on a bunch of projects, but it's really hard work to do a good job.

My main question is, how particular is all of this to bioinformatics and evolutionary biology, vs all of data-intensive science? Having just attended a workshop on this stuff, I'm skeptical that anyone is really doing an even passable job. I'm not even sure what solutions are on the horizon, at least in bioinformatics. Yikes.

One final note: while I was writing this up, I realized that these perhaps overly high standards may be sourced in my testing work, from software development. I know from firsthand experience just how context- dependent specific (and often very important) outputs can be from tracking down bugs in software; since computational science is at least as hard as software development, I infer the same is true there. Interesting.

--titus


Legacy Comments

Posted by Andrew Davison on 2011-12-07 at 03:34.

Hi Titus,    Thanks for the post. I can confirm that none of these
issues are particular to bioinformatics. At least, they are a major
problem in neuroscience and neuroinformatics as well, although people
doing neuroimaging seem to have a better handle on this than most.
Although I can't offer you AuditTrail2000, I have been working on some
(open-source) software for automatically capturing the context (code
versions, parameters, platform, inputs and outputs) of scientific
computations. It is perhaps a possible basis layer for an audit trail
system, rather than a full blown solution. Anyway, if you're
interested in taking a look I'd be very interested in your feedback:
<a href="http://neuralensemble.org/sumatra">http://neuralensemble.org/
sumatra</a>    Another tool that seems to provide a good audit trail
for computational pipelines is VisTrails (http://www.vistrails.org),
although it requires that your code is appropriately wrapped to fit
within their workflow system. There are other workflow systems out
there, but I find VisTrails particularly interesting (although I
haven't yet tried to use it for a real project) because (a) it has a
particular focus on provenance and (b) it's written in Python, so
wrapping my own code to fit within it should be straightforward.
Cheers,    Andrew

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