We find ourselves wondering why codon adaptation index (CAI) is used as a measure of protein expression level in this article.

One answer is that CAI does correlate well with protein expression in many proteomics studies; but surely these same studies contain raw data with protein expression level? On reflection, I bet the answer is that it’s too difficult and laborious to access this type of data. There are plenty of papers that describe large-scale analysis of protein expression using proteomics, but the data are locked up in the articles or as inappropriate supplementary files.

Note to self: look into open-source software and standard data formats for proteomic data.

It’s turned out to be a pretty good week. This one has been in press for ever, but finally hit the web:

Frith, M.C., Saunders, N.F.W., Kobe, B. and Bailey, T.L. (2008).
Discovering Sequence Motifs with Arbitrary Insertions and Deletions.
PLoS Computational Biology 4(4):e1000071. [Open Access] | [PubMed]

This paper describes GLAM2, a Gibbs sampler that finds and refines variable-width motifs, allowing insertion and deletion, in related but dissimilar sets of sequences. The work is Martin’s baby; my very minor contribution was to try it out on some test datasets. It’s open-access and open source, so you can all go and enjoy it then grab the software to try.

Two more (unrelated) in press to tell you about soon. See, I do have a day job outside of this blog.

Who isn’t fascinated by the strangest of mammals, the platypus? It has fur and lactates, like a mammal. It has a bill and webbed feet, like a bird. It lays eggs and produces venom, like a reptile. It finds prey using electroreception, like sharks. The platypus is so weird that when first described, many scientists assumed that it was a hoax.

To celebrate the publication of the draft platypus genome, here’s a brief guide to this wondrous creature.

Part 1. The Dreamtime Story
We scientists think that we’re very smart when it comes to explaining the natural history of Australia. However, the original inhabitants of this country have a rather different and quite compelling explanation, which goes by many names, but is most often known as the Dreaming. During the Dreaming, ancestral spirit beings in the form of animals wandered across the land, leaving behind their offspring, descendants and landforms.
To aboriginal people, the platypus was clearly half-water-rat, half-duck. There are several stories that explain the origin of this strange animal, but most of them concern a female duck (often named Daroo) and a wiley, male water rat, named Biggoon, or sometimes Bilargun. It goes like this.

“Daroo the Duck lived with other ducks in a secluded pond and all were in fear of the Mulloka, or Water Devil, which lurked in deeper waters. Thus, they never strayed far from their pond. One day, however, Daroo decided to disobey the elders’ advice and ventured out downstream. She stumbled across the territory of the “Water Devil”, Bilargun the Water Rat. He threatened duck with his spear when she tried to flee, and dragged her underground into his burrow. He forced her to mate with him, and she remained his captive for weeks before escaping.
When it came to hatching season, all the other ducks emerged from the reeds to parade their newborn ducklings. On the other hand, Daroo was ashamed to lead out two extraordinary offspring. They had fur instead of feathers, a bill and webbed feet, and a spike on each hind leg, reminiscent of the Water Rat’s spear. Daroo was ashamed and taunted, so she left the pond with her offspring, the first of the platypuses.”

Part 2. The Island Continent
So here’s the alternative version. Around 170 million years ago a landmass named Gondwana, made up of most of the continents in the present-day southern hemisphere, began to drift apart. A large portion of East Gondwana initially headed south, but about 50 million years later the northern part changed its mind, deciding to become India and Madagascar. Some 40 million years after that, the Indo-Australian plate also had a change of heart, rotated around and set off north once more. Gradually it separated from Antarctica, the ocean around its coastlines widening and deepening and so the island continent of Australia and neighbouring New Guinea was born.

On board the new island was a cargo of small creatures that to our eyes, must have resembled furry reptiles. Isolated from the rest of the world, they would eventually diversify into the mammal species of Australia. It just so happened that the environmental conditions in this new land favoured certain types of mammal more so than in most other parts of the world. One group, the marsupials, developed external pouches in which to nurture their embryonic young and took to hopping around on their hind legs. Another group, the monotremes, went off in an all-together more bizarre direction. This road will lead to two very different monotremes: a spiny, land-dwelling ant-eating creature called an echidna and an aquatic animal, the modern-day platypus.

Part 3. The Colonists
Fast-forward another 80 million years to the present day, or as good as: 1798. It’s 10 years since the First Fleet sailed into Port Jackson to establish the colony of Sydney. The second governor of New South Wales, John Hunter, is a keen amateur naturalist and has watched an aboriginal hunter spear what the settlers call a “water mole”. He sends the skin with an accompanying sketch back to England, where it is received by a curator at the British Museum named George Shaw.

Part 4. The Journal Article
You’ve probably never read the journal The Naturalist’s Miscellany: or Coloured Figures of Natural Objects Drawn and Described Immediately from Nature but in 1799, it was an important natural history journal. It’s also where Shaw described the animal that he named Platypus anatinus, flat-foot duck. Shaw, like many others, could barely contain his scepticism:

“Of all the Mammalia yet known it seems the most extraordinary in its conformation; exhibiting the perfect resemblance of the beak of a Duck engrafted on the head of a quadruped. So accurate is the similitude, that, at first view, it naturally excites the idea of some deceptive preparation by artificial means…”

The creature was later renamed Ornithorhynchus anatinus, but the word platypus was kept for the common name. Once scientists accepted that it was not a hoax, they realised that the platypus occupied an important position in mammalian evolution. The big question was: did it lay eggs? After much debate, a Scottish zoologist named William Hay Caldwell demonstrated that they do and sent a succinct, four-word telegram to the annual meeting of the British Association for the Advancement of Science in Montreal: “Monotremes oviparous, ovum meroblastic.”

Part 5. The Genome
210 years after the platypus was first described, the draft genome of a female specimen called Gennie appears in Nature.
When you look at a platypus, your first thought is: it’s part mammal, part bird, part reptile. What’s really cool about the Nature publication is that when you look at the platypus genome, you see exactly the same thing. Here are some of the highlights:

• Platypus have multiple sex chromosomes; the males have 5 X and 5 Y, which segregate into 5X and 5Y sperm
• How these combine to determine sex and gene dosage is not understood
• The X chromosomes are similar to bird Z but not human X, implying a bird-like ancestor for the platypus X
• The same gene duplications responsible for venom production arose independently in reptiles
• The platypus immune system has several unique features; in particular, a far large number of natural killer receptor genes than any other mammal
• In general, the protein-coding genes exhibit a mosaic of mammalian (e.g. milk production) and reptilian (e.g. egg-laying) features
• The non-coding protein genes include 10 times as many predicted snoRNAs as therian mammals and a variety of miRNA candidates, most of unknown function

It’s clear from the paper that we’ve only just begun to use genomics to understand monotreme biology and compare the prototherian mammals with their therian relatives. Let’s hear it for the platypus; bizarre mammal supreme and Australian icon.

Further reading

• Genome analysis of the platypus reveals unique signatures of evolution. Nature 453: 175-183. Abstract | Full text
• Relevant abstracts from Genome Research Platypus Genome Special
• Hall, B.K. (1999). The Paradoxical Platypus. BioScience 49(3): 211-218. JSTOR link

This is a wonderful historical account and should be made more widely available.

• Platypus biology at the Australian Platypus Conservancy

Nothing exciting - just a couple of notes on the Ubuntu upgrade experience from 7.10 to 8.04.

• Machine #1: LG Express Dual T1-72C1A laptop, Intel GMA950 graphics card

Pretty much a flawless upgrade

• Machine #2: Desktop cobbled together with all sorts of bits over the years; problem feature being ATI Radeon 9600XT graphics card
• Garbled screen on reboot; my own fault due to multiple, conflicting fglrx + compiz modules; went for a clean install
• Seems Ubuntu have packaged a working fglrx + compiz combo; X11 radeon used by default but gives you the option to switch to fglrx on first login; works fine with compiz (except for known GL flicker problem), even has TV-OUT!
• Compiz ccsm (advanced manager), emerald decorator and tray icon (fusion-icon) not installed by default
• System in general pretty snappy; Firefox 3 a revelation

I’m amazed at the improvement in Firefox 3. Slow page loading that I’d attributed to poor internet connections or bad graphics card configuration was, in fact, poor Firefox 2 rendering.
Downside: very few extensions compatible - seems odd, given that FF3 has been in beta quite a while. There are hacks to use your old ones, but I don’t recommend them. Good news: the extension that I can’t live without (del.icio.us) has an FF3 version here. The new mysocial24×7 works too.

Firefox screenshot, from left to right: Vertical tabs, courtesy of Vertigo - because you can never have too many tabs Main window: the feeds roll into GReader On the right, almost all the functionality of FriendFeed (except search) in fantastic new extension MySocial 24×7 On the right? Yes, because sidebars look better on the right IMHO, made possible by MultiSidebar

Tenuous bioinformatics connection: well, you work more effectively if you’re happy with your browser setup

ResolveRef, a RESTful way to resolve PubMed queries by journal, year, volume and page is Andrew’s port of OpenRef to App Engine. Simple, but very effective and a nice illustration of how to get to grips with the App Engine environment.

Keep those “App Engine apps for researchers” rolling in, folks.

It’s been ages since I visited the R website, so I don’t know how long they’ve had a wiki. It’s built using DokuWiki, one of my personal favourites.

This is a great leap forward for R documentation, which is somewhat notorious for being (a) difficult to find and (b) difficult to understand when you find it. If you’re a power R user and have a spare moment, please contribute.

This blog seems to become more about social networks/open science and less about bioinformatics every week. Perhaps that’s no bad thing. Here’s a few highlights from the activity stream this week.

• From Depth-First: User-Created Compound Monographs on Chempedia.net on the Web 2.0 approach to chemical encyclopedias
• Post of the week: in response to One Big Lab, Cameron on the science exchange
• In response: Deepak on micro-funding; thankfully one of us has a business mind
• Science Commons asks are you part of open science?
• And the iPlant Collaborative takes affirmative action on science collaboration (some nice-looking jobs at CSHL posted there)
• Nature Network announce plans for a European Science Blogging Conference
• Also from Nature Network, a record 100 comments for Jennifer’s post; admittedly the last few are silly ones to get her over the line
• UsefulChem points us to an article in Cell on open-source drug discovery
• From Bioinformatics, a follow-up to the “404″ study (thanks Paulo!); take-home message is that academics probably shouldn’t run webservers
• Rosie’s long, blog-less teaching stint is over; she returns with a discussion about making shared code readable
• Finally from the “things that made me laugh” department: Facebook group pop songs as graphs (thanks Graham)

The Twitter + FriendFeed combination is proving to be a very useful information stream; not just from other people but as a reminder of what I thought was worth sharing. Two links from there that I think deserve wider attention:

• One Big Lab proposes that we become, well, one big lab - and has some ideas as to how that might work.
• From the OWW wiki, an excellent article on python in computational biology. This has been presented at Pycon 2008 and is also a companion article to a paper in PLoS Computational Biology. Imagine if everyone described their methods in this detail.

Deepak has some commentary on what we’re now calling the “bio-twitterverse”.

…with a biologically-relevant application for Google App Engine, is Euan with pycite, a port of Connotea. Man, this makes me want to learn Python fast.

More thoughts and commentary at Deepak’s blog.