This week began rather hectically for me. Time to chill with this Jazz classic.
Nir London has recently started a poll asking “what is your favorite molecular viewer?” I voted for RasMol. As you can see from the results, I am in a low single-digit minority (4% when I am writing this). PyMOL (35%) VMD (27%) are leading. Why did I not vote for one of those? PyMOL is the de-facto standard for creating presentation movies and publication quality figures. It is also Python-scriptable, which is always a good thing. VMD is geared towards Molecular Dynamics analyses, but also produces great figures and has lots of nifty features. Both have their source-code made available under different licenses. PyMOL is dual licensed, with some features available on a paid basis; I’m cool with that.
If PyMOL and VMD are the Cadillac & Lexus of viewers, RasMol has to be the Vespa. It gets you there, but not in any kind of comfort, and there are lots of things it won’t do, missing two wheels and a roof; it gives you a bad image and bad hair when you ride it. It’s not even obviously cheaper: the vehicle analogy breaks with the price, since all three are free (as in beer and as in code). So why do I ride the Vespa when the Cadillac costs the same?
March 14 is also the anniversary of the release of Linux kernel 1.0, with all of its 176,250 lines of code. The current 2.6.28 has crossed the 10,000,000 threshold.
Tux should have a birthday Pi…. but here is some other Tux confectionery:
Happy Pi (π) Day! Americans write dates in the MM/DD/YYYY format instead of the DD/MM/YYYY format used by the rest of the world. Usually a rather painful and confusing format if you did not grow up with it, causing checks to bounce and leases to expire for those who recently moved to the US, but it has a few benefits: you can take the numeric representation of March 14, and you have the first three digits of Pi. This coincidence is good enough to celebrate a day around the uber-celebrity of numbers. (Heh, I said “around”). Everybody’s welcome.
This is the day all geeky bloggers come out and try to: (1) show how smart they are; (2) connect Pi, usually in some improbable and tenuous fashion, to whatever theme they have in their blogs and (3) try to make an original observation of pi no one else has made before. So that is exactly what I am going to do today.
Well, probably not.
Well, I remembered Pi day, didn’t I? OK, that does not show I’m smart, just shows my brain is a repository of useless trivia. Look at the time of publication of this post: March14, 1:59am which is 3.14159. Hey, five digit time stamp that’s smart! (Not very original though, also I’m actually up at this time finishing a grant proposal).
A post with a less than tenuous connection to Pi
Some virus capsids are icosahedral. Not really spherical but sort-of. Bacteria have flagella motors that are circular. Micelles are usually spherical. Microvesicles are spherical. All these are a good start for pi-topics.
Well, too bad. I actually want to write about circular proteins. Only “circular” in this case does not mean “circle shaped”: hence, we are chucking Pi out the window right now. Stick around though, these proteins are really cool.
You were probably taught that proteins are linear chains of amino acids that fold into a shape that produces their function. The links connecting the chains are peptide bonds. But there is no real reason why the carboxy terminus (right side) and amino terminus (left side) would not bond themselves. It just has never been observed, or looked for. Well, they do. And some proteins are circular, like a snake biting its own tail.
These cyclotides are very robust. For one, they are almost immune to proteases: enzymes that break up proteins. Many proteases attack the edge of the protein (exoproteases, because they start from the “outside”), but there are no edges to attack here. The disulfide bonds, their short length make them immune to endoproteases as well as to heat, pH, etc.
What do cyclotides do?
They protect the organism that produces them. All kingdoms of life produce cyclotides, everything from bacteria to Rhesus monkeys. (Actually, I am not sure about Archae). Cyclotides seem to act in different mechanisms: some form holes in the membrane of the attacking microbe; plant cyclotides stunt the growth of feeding caterpillars. Interestingly, the same plant peptide, Kalata B1 induces uterine contractions in mammals. This is how it was discovered: a physician working in the Democratic Republic of Congo noticed that laboring women were drinking tea made from Oleanda affinis to induce childbirth. Theactive ingredient was the first cyclotide to be discovered. Since then, cyclotides have been shown to be antibiotic, antiviral and insecticidal.
Do humans produce cyclotides?
I could not find anything about that in the literature. So I took the amino acid sequence of a recently discovered monkey cyclotide, rhesus theta defensin 1 (RTD1) sequence and BLASTed it (TBLASTN: protein vs. nucleotide) against the human genome. No results. Of course, this 5 minute trial proves very little. TBLASTNing short sequences (the RTD1 is only 18aa long) is a bit sticky. If you are a beginning bioinformatics student looking for a course or rotation project, finding candidate Cyclotides in humans (or in other genomes) might be a good idea. There are about 100 known sequences, so quite a bit for a training set to start from. You can build a profile or an HMM, and do some more sensitive searches.
But what about Pi?
Sigh.. well, here is an XKCD oldie but goldie nerd litmus test… enjoy…
Trabi, M. (2002). Circular proteins — no end in sight Trends in Biochemical Sciences, 27 (3), 132-138 DOI: 10.1016/S0968-0004(02)02057-1
PELEGRINI, P., QUIRINO, B., & FRANCO, O. (2007). Plant cyclotides: An unusual class of defense compounds Peptides, 28 (7), 1475-1481 DOI: 10.1016/j.peptides.2007.04.025
Wang, C., Hu, S., Martin, J., Sjogren, T., Hajdu, J., Bohlin, L., Claeson, P., Goransson, U., Rosengren, K., Tang, J., Tan, N., & Craik, D. (2009). Combined X-ray and NMR analysis of the stability of the cyclotide cystine knot fold that underpins its insecticidal activity and potential use as drug scaffold Journal of Biological Chemistry DOI: 10.1074/jbc.M900021200
Most of the Earth’s surface is colder than the inside of your refrigerator. Deep sea temperatures are almost universally 2-4C. That’s already 73% of the Earth’s surface. Then add to that the polar regions, mountain ranges and permafrost and you have about 85% of the Earth’s surface constantly at refrigerator or freezer temperatures. While there are many microbes adapted to life at those temperatures, microbiology has historically been dealing with mesophiles (“middle [temperature] loving”) that with psychrophiles (“cold lovers”). This is mostly for historical and practical reasons: medical microbiology has always been dominant and our body temperature is 37C. Another historic branch of the development of microbiology was the food industry, and most processes in that branch take place at temperatures between 10 and 40 C. Indeed we pasteurize milk at 60C, and then store it at 4C to stave off curdling by bacteria.
Anyone who failed to empty their milk carton on time knows that some microbes do eat (and therefore grow) at near-zero temperatures. Nevertheless, we don’t know about cold bacteria, even though as we have seen, most of the real estate on Earth is cold. Also, if we were to find life in the solar system, it would probably be found on the cold moons of Jupiter and Saturn, in the Martian ice caps, or in subsurface Martian ice. The first step to understand how life might exist there, is to understand how it exists in the cold here.
The first time I heard Charlie Musselwhite was on KSDS 88.3, San Diego’s jazz radio station and one for the finest jazz & blues stations I know.
I was driving, it was late night and raining, and I was dead tired; the perfect setting for some blues. They played Musselwhite’s jumpy “Both Sides of the Fence” from his album Rough News. Charlie’s dominant harp, strong voice and rhythm captivated me. I bought the CD the next day.
This is another song from that album, performed here by Charlie and his daughter Layla.
When the Moon is in the Seventh House, and Jupiter aligns with Mars, a bunch of people gather for their “Bioinformaticians anonymous” group therapy. There they metaphorically gather, commiserating about how bioinformatics is dead (or was it bioinformaticians?), just smells funny or suffers from identity theft, probably because it got drunk at the last ISMB, passed out, and left its driver’s license, along with most of its cash on the dresser at some room.
OK, I don’t like the term “next generation sequencing”. It is a relative term, points at a changing target, and therefore inexact. What is the “this-generation sequencing”? Sanger? 454 used to be “next generation”, but now 454 sequencing went from 100bp to 600bp per read, making it qualitatively different.. so “post-next generation sequencing”? If you want to describe a sequencing technology call it what it is: title the technology by something more descriptive than a relative term that has built-in obsolescence, even the company name & machine is better. That’s what everybody use in their lab conversation & emails anyway. Illumina/SOliD is “short read”, 454 is “pyrosequencing”, Pacific Biosciences is Single Molecule Real Time, etc, etc.
Having got that out of my system, here is the latest cool thing, this time from Oxford Nanopore: an exonuclease trims off the bases one by one. Those go into a membrane pore with an adapter molecule that recognizes the nucleotide going through it: it can even recognize methylated Cytosine, commonly referred to as “the fifth DNA base”.
James Clarke, Hai-Chen Wu, Lakmal Jayasinghe, Alpesh Patel, Stuart Reid, Hagan Bayley (2009). Continuous base identification for single-molecule nanopore DNA sequencing Nature Nanotechnology DOI: 10.1038/nnano.2009.12
But if you know what life is worth, You will look for yours on Earth -- Bob Marley
– “Is there life on Earth?”
– “Well, duh.”
– “I mean, is there another kind of life on Earth?”
– “You know… there could be these bugs that, like, they’re all around us and we don’t know they are there because that’s not the life we recognize”.
– “Whoa, dude, hea-vy”
Actually, this conversation may not be as sophomoric or THC-laced as I made it out to be. OK, OK. obviously it is sophomoric and THC-laced, but I put a quote from Marley not for the cannabis allusion, but for the literal interpretation: looking for Life on Earth.
– “Seriously dude, WTF?”
Could life have arisen on Earth more than once? If so, can we find evidence of this happening? Even more so: could this “weird life” still exist here undiscovered?
I have been traveling to Ohio a bit recently… one of my favorite bands (a duo really) comes from Akron, OH. The Black Keys. First song of them I heard was this one, Thickfreaknes; still one of my favorites.
Biopython is entering its 10th year; the unofficial birthday is on September, since that is when the mailing list started: September 1999. I stumbled onto that list mid-September, 1999. I believe the Python version was 1.5, I was still working on SGI Irix, and I was an 0.3 PhD candidate. Today I am coding with Python 2.5 on Ubuntu Linux 8.10, Biopython 1.49, and I am a scientist 1.9 (I hope to roll a new release of myself soon). Biopython started out when Perl dominated the Bioinformatics scripting language scene. Jeff Chang, then a PhD candidate in Russ Altman’s lab in Stanford thought it would be a cool idea to have a Python package for Bioinformatics. If there are three people that deserve credit for Biopython those are Jeff Chang, Andrew Dalke and Brad Chapman. These three contributed most of the code and design that made Biopython such a robust and useful package; of course, there were and are a lot of others involved, including myself. By the time I was finishing up my dissertation in late 2002, I think that 95% of my code was importing biopython modules, some of them coded by yours truly.
Happy Darwin Day! If you are reading this then you probably do not need an introduction to Charles Darwin, the importance of his work, how his theory of evolution by natural selection shaped modern Biology. Or if you do, I bet there are plenty of posts in today’s blogswarm that will address this.
There is one evolutionary force that I would like to talk about on this special day, and that is the force of mass extinction. Over the history of the Earth, fossil records show us that there have been five mass extinctions, or as palaeontologists refer to them “The Big Five”. The most famous and best understood of mass
extinctions is also the most recent one: the Cretaceous-Tertiary or KT extinction 65.5 million years ago (Ma),thought to be caused by an extraterrestrial object impacting in the area of what is now Chixclub in the Yucatan peninsula, Mexico. The impact (or a combination of the impact and previous volcanic activity) caused the mass extinction of some 60% of terrestrial and 70% of marine species; most famously, the dinosaurs. Fossil records tell us of four more mass extinctions, some larger in scope of species death than the KT.