The four most stupid things I have ever done in bioinformatics.

It was a cold November morning, year 2011. Sapienza University has a huge campus next to the city centre of Rome, where the main faculties are stored in huge buildings in the rationalist style. Yet, the faculty of Biochemistry has a detached site in the neighboured flanking the campus, San Lorenzo. I was crossing the streets of this wonderful ex-industrial alternative hood to reach my new lab. The clock was marking 10:30 AM, and I was joining bioinformatics. Professor Stefano Pascarella had accepted to supervise me in my master thesis, and it was my very first day. Four years have passed, I have graduated, worked in five different labs, and even if my experience is not really long, I think I have already a couple of stories to tell.

Stupidity matters. Despite the most of the people use to link science to intelligence and genius, seeing research as a matter of the “smart guys”, we must admit that the lab routine is often studded with the crap we make, and that researchers can become protagonists of actions of remarkable stupidity. And if we scan the first, faltering steps of a researcher’s career, we may find a couple of funny nerdish stories to tell with colleagues in a bar. And since I’d be so sorry to know that someone of you may run out of funny anecdotes about grad students’ stupidity to tell, let me report the four most stupid things I have ever done in bioinformatics.

Trying to fetch information from uniprot on 1750 genes without any programming

Munch_The_Scream_lithography
The first task of my master thesis was simple. My advisor provided me with a list of 250 uniprot IDs of MocR proteins in several bacterial genomes. Helix-turn-helix transcriptional factors, with an amminotransferasic domain allosterically regulating them by pyridoxal-5’-phosphate binding. The lab had identified these sequences with HMMer, and we wanted to know something more about the flanking regions. The professor told me to annotate 3 upstream and 3 downstream coding regions in order to see wether some recurrences could indicate a conserved multigenic region; simple and straightforward.

The next day I was shattered, reclining a lost look on my screen, at 8 pm and after ten hours of work. A hard lesson that I have learned by the time, is that if you did something wrong in designing your bioinformatics workflow, a spreadsheet will show up at a certain point. I was staring at an OpenOffice Calc window with about 40 rows, and had managed to find a way to manually scan the flanking region. I don’t remember exactly my glorious strategy, but it should have sounded like this:

  1. Copy and paste the id on uniprot and search it.
  2. Scroll the way down to the crosslink pointing at a graphical genome browser and open it.
  3. Perfect, you are on the spot! Now move the browser forward and back, you will find the flanking sequences.
  4. Select any flanking gene in the interval and make your way back to uniprot
  5. Save the information you get (the Uniprot ID basically) on a spreadshit and go on

I was then suggested to stop doing this and go further with studying python. That was the day when I learned that there is no bioinformatics without programming.

The protein-DNA docking to fetch promoters.

Doc-BrownAfter the first explorations, the final goal of my M.Sc. thesis work became the identification of a conserved promoter region upstream the neighbouring genes pdxS and pdxT, coding for the two subunits of the pyridoxal-phosphate polymerase holoenzyme in bacteria. This memory tastes a bit sweet, as usual when you end up remembering how naive you were when just a newbee. It was the early 2012, January or maybe Feburary. During a lab meeting, I argued that a good option to find our promoters was to perform a docking analysis on a set of candidate promoter sequences, docked with the MocR transcriptional factor that was found activating their transcription. After having explained my point, I realised that anyone was just looking at me with dismay. Do you know that awful feeling of anyone in the room looking at you like you’re crazy? I was explained that the methods developed for protein-DNA docking were still too ineffective to fetch a reliable result. Protein – DNA docking to infer the binding region of an HTH? Pure science fiction. At least, that day I have been introduced into one of my favourite topics in bioinformatics: the communication between DNA and proteins.

Declaring profanities as variables in your code.

1142382632_swearing_xlargeEven if I am quite used at threading jokes in my code, taking it as a “nerdish rebellion” against my even more nerdish work routine, what I am going to tell here didn’t actually happen to me. I include this story I have heard of in my post because it’s really worth reading.

In team-working sharing code is fundamental, and the best habit you can take is to write variables in a human language, and to write proper comments in order to get the people who will read your code to understand it (to any possible extent). Anyway, the first thing you should care about before sharing your code is to make sure that it won’t worsen the opinion your colleagues have about you.

This story has all the ingredients that a good academic joke needs to succeed: a polite and old-mannered thesis director, a graduate student with a sense of humor that his advisor won’t get, swear words, profanities, and a Perl script to show them up.

Stefano Pascarella is not old at all, but he is still the kind of super-mannered and polite Italian professor. I worked in his lab for two years long, and never heard him yelling at anyone or just expressing disappointment with harsh. Quite remarkable, since he was my thesis advisor. Instead, I never met the student who’s the protagonist in this story, and I can just assume him as the typical 20-something master student. The only thing that I am pretty sure about him is that one day he wasn’t at the lab, and his code was needed for some reason.

Professor Pascarella sat down in front of the terminal and rapidly found the file he needed. The people who told me this story just can’t forget the expression on professor’s face. A calm and bored expression ran immediately into a serious face, that swiftly faded into disconcert. Any given variable of the code he was reading was either a bad word or a profanity.

Later on that day, the student received a mail “kindly asking” him “to take his coding routine more seriously”.

Ignoring the find/replace function in a text editor.

maxresdefaultOk, I am figuring out what you are thinking. “This moron didn’t know that text editors had a find/replace function and corrected a whole code manually to change a single word”. Not so, I did something that is possibly worse. When I started to write code, actually I did not know much about the existence of this amazing function in my text editor, but I was still very sure that the process had to be automatised. My ignorance on text editors mixed dramatically with my inclination to programming to give rise to one of the most stupid things I have ever done.

As I finished and tested the script named changeword.py, I was totally sure that it was one of the best things I could produce with my short programming experience. I don’t really remember the code, but it should have sounded as follows:

#! /usr/bin/python
import sys
filein = sys.argv[1]
word_to_change = sys.argv[2]
replacement = sys.argv[3]
a = open(filein,’rU’)
b = a.read()
a.close()
print b.replace(word_to_change,replacement)

To run it, you just needed to input the file and the word you wanted to change with its replacement, and anything went to the standard output:

$> ./chageword.py my_file.txt first_word second_word > my_corrected_file.txt

Et voilà, the text came out changed. Luckily, at a certain point I realised that my fantastic script didn’t work for any change I could need, and decided to discuss this problem with a postdoc in my lab. He is still laughing about this.

Write the MD5-checksum code on the same file from which I extracted it.

MKSB023_UselessMachine_Animation_largeFatigue plays tricks, and makes a perfect source of inspiration for stupid actions. When you are tired you can experience severe logical failures, and brightly shatter your work in seconds.

This happened a few months ago. Tracking your input, output and script files is very important, and even if we are not used at version control systems, annotating any file with its MD5 code may help, to some extent, in having a better tracking of your work.

The MD5 algorithm assigns a unique code given an input. If you input a file to the MD5, the output code will correspond to that file univocally. Of course, if you modify the file the resulting MD5 code will change.

I was finishing a long scripting course and was adding information on my output tabbed file in an hashed header. As I calculated my MD5 code, I had the brilliant idea to write it on the same file from where I extracted it. Not to mention that after having pasted the MD5 code on the file, the MD5 code of that new file inexorably changed.

It took to me a good quarter of hour to realise it. It was 9 PM, and I thought it was just my brain asking me to go home for some rest.

As I said at the beginning of this article, stupidity matters. And ironising at yourself matters even more. Cognitive work requires the application of all your rationality, and it is thus fundamental to understand its limits, or else the borders of your intellectual skills that are shaped by stupidity. I think that there is no shame in recognising you own limits, and publicly admitting them is someway therapeutic.

Quoting an Italian PhD student I have met at my department who recently graduated, “there is no use for a PhD course except in the light of understanding how stupid you are”. I have recently registered for my second year of PhD here at the CRAG, and still have a long way ahead to explore the deepest corners of my stupidity.

After all, the Diesel advertisement showed as heading image of this post, may be right. You are stupid only if you try to explore your limits. And this is right about what I am up to.

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