Celebrating an unsung hero of genomics: how Albrecht Kossel saved bioinformatics from a world of hurt

The following image is from one of the first publications to ever depict a DNA sequence in a textual manner:

From Wu & Kaiser, Journal of Molecular Biology, 1968. 

From Wu & Kaiser, Journal of Molecular Biology, 1968. 

This is taken from the 1968 paper by Wu and Kaiser: Structure and base sequence in the cohesive ends of bacteriophage lambda DNA. For almost half a century since this publication, it has become the norm to simply represent the sequence of any DNA molecule as a string of characters, one character per base. But have you ever stopped to consider why these bases have the names that they do?

Most of the work to isolate and describe the purines and pyrimidines that comprise nucleic acids came from the work of the German biochemist Albrecht Kossel. Between 1885 and 1901 he characterized the principle nucleobases that comprise the nucleic acids: adenine, cytosine, guanine, and thymine (though guanine had first been isolated in 1844 by Heinrich Gustav Magnus). The fifth nucleobase (uracil) was discovered by Alberto Ascoli, a student of Kossel.

Kossel's work would later be recognized with the 1910 Nobel Prize for Medicine. It should be noted that Kossel didn't just help isolate and describe these bases, he was also chiefly responsible for most of their names.

Albrecht Kossel, Image from wikimedia

Albrecht Kossel, Image from wikimedia

Guanine had already been named based on where it had first been discovered (the excrement of seabirds known as guano). Adenine was so named by Kossel because it was isolated from the pancreas gland ('adenas' in Greek). Thymine was named because it was isolated in nucleic acids from the thymus of a calf. Cytosine — the last of the four DNA bases to be characterized — was also discovered from hydrolysis of the calf thymus. Its name comes from the original name in German ('cytosin') and simply refers to to the Greek prefix for cell ('cyto').

While this last naming choice might seem a little dull, all bioinformaticians owe a huge debt of thanks to Albrecht Kossel. Thankfully, he ensured that all DNA bases have names that start with different letters. This greatly facilitates their representation in silico. Imagine if he had — in a fit of vanity — instead chosen to name these last two bases that he characterized after himself and his daughter Gertrude. If that had been the case then maybe we would today be talking about the bases adenine, albrechtine, guanine, and gertrudine. Not an insurmountable problem to represent with single characters — we already deal with the minor headache of representing purines and pyrimidines differently (using R and Y respectively) — but frankly, it would be a royal pain in the ass.

Thank you Albrecht. The world of bioinformatics is in your debt.

The growth of bioinformatics papers that mention 'big data'

I very much enjoyed Stephen Turner's recent blog post There is no Such Thing as Biomedical "Big Data" and I agree with his central point that a lot of the talk about 'big data' is not really what others would consider 'big'. Out of curiosity, I had a quick dive into Google Scholar to see just how popular this particular cliche is becoming. My search term was "big data" biology|genomics|bioinformatics.

Growth of bioinformatics papers on Google Scholar that mention "big data".

Growth of bioinformatics papers on Google Scholar that mention "big data".

Clearly, this term is on the rise and might become as much of an annoyance as another phrase I loathe: next generation sequencing. A phrase that has been used to describe everything from 25 bp reads from early Solexa technology (circa 2005) to PacBio subreads that can exceed 25,000 bp.

As more people use N50 as a metric, fewer genomes seem to be 'completed'

If you search Google Scholar for the term genome contig|scaffold|sequence +"N50 size|length" and then filter by year, you can see that papers which mention N50 length have increased dramatically in recent years:

Google Scholar results for papers that mention N50 length. 2000–2013.

Google Scholar results for papers that mention N50 length. 2000–2013.

I'm sure that my search term doesn't capture all mentions of N50, and it probably includes a few false positives as well. It doesn't appear to be mentioned before 2001 at all, and I think that the 2001 Nature human genome paper may have been the first publication to use this metric.

Obviously, part of this growth simply reflects the fact that more people are sequencing genomes (or at least writing about sequenced genomes), and therefore feel the need to include some form of genome assembly metric. A Google Scholar search term for "genome sequence|assembly" shows another pattern of growth, but this time with a notable spurt in 2013:

Google Scholar results for papers that mention genome sequences or assemblies. 2000–2013.

Google Scholar results for papers that mention genome sequences or assemblies. 2000–2013.

Okay, so more and more people are sequencing genomes. This is good news, but only if those genomes are actually usable. This led me to my next query. How many people refer to their published genome sequence as complete? I.e. I searched Google Scholar for "complete|completed genome sequence|assembly". Again, this is not a perfect search term, and I'm sure it will miss some descriptions of what people consider to be complete genomes. But at the same time it probably filters out all of the 'draft genomes' that have been published. The results are a little depressing:

Google Scholar results for papers that mention genome sequences or assemblies vs those that make mention of 'completed' genome sequences or assemblies. 2000–2013.

Google Scholar results for papers that mention genome sequences or assemblies vs those that make mention of 'completed' genome sequences or assemblies. 2000–2013.

So although there were nearly 90,000 publications last year that mentioned a genome sequence (or assembly), approximately just 7,500 papers mentioned the C-word. This is a little easier to visualize if you show the number of 'completed' genome publications as a percentage of the number of publications that mention 'genome sequence' (irrespective of completion status):

Numbers of publications that mention 'completed' genomes as percentage of those that mention genomes. 2000–2013.

Numbers of publications that mention 'completed' genomes as percentage of those that mention genomes. 2000–2013.

Maybe  journal reviewers are more stringent about not allowing people to use the 'completed' word if the genome isn't really complete (which depending on your definition of 'complete' may include most genomes)? Or maybe people are just happier these days to sequence something, throw it through an assembler and then publish it, regardless of how incomplete it is?

2013 ended with a bumper crop of new JABBA awards for bogus bioinformatics acronyms

jabba logo.png

I have a huge backlog of JABBA awards to hand out. These are all collated from the annual publication of the (voluminous) 2013 Nucleic Acids Research Database Issue. So without further ado, here are the recipients of the latest batch of JABBA awards:

Honorable mention: