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Posts Tagged ‘nucleotides’

A Chinese computer scientist has a suggestion: mimic the way search engines index Chinese characters.

Technology Review's blog helpfully describes why search engines like Google are so fast and why current bioinformatics search systems are not. Most search engines use an inverted index -- rather than compiling a list of every single Web page and all its words, for every single word, they compile a list of the places where it appears.

Bioinformatics searches, by contrast, use a couple algorithms that basically compare the data from one genome to the data from another. This is relatively fast when there are only a few genomes, but as they grow exponentially, the searches take much longer.

A simple solution would be to switch to the Google approach -- for every base pair "word," make a list of the genes where they appear. But words are easy to spot, because they have spaces between them. Base pairs do not.

As it happens, Chinese characters don't, either, but search engines have gotten around this. Wang Liang, a computer scientist at SOSO.com, one of the big three search engines in China, says the trick is to segment the words into "n-grams," words that are n letters long.

Tech Review explains: There are 1-grams for one-letter words, 2-grams for two-letter words and so on. A search for a 3-letter word, like ABC, can be done by searching for AB and BC. Some Chinese search engines work this way, by indexing all the 2-gram combinations.

OK, then, how many n-grams are in a genetic word? The nucleotides A, T, G and C are only 1-grams, which makes them pretty useless as search terms. So some fuzzy math is required. Liang says DNA sequences follow Zipf's law, which basically states that in any long document, half the words appear only once. This theory can be used to find an average length for DNA "words."

Liang studied the genomes of arabidopsis, aspergillus, the fruit fly and the mouse, and found that a good average word length is 12 letters. Therefore, the best way to index genome data is to use 12-grams -- that is, 12-letter combinations of A, T, G and C.

With that vocabulary, a Google-like inverted index becomes possible.

[Technology Review]

It's hard to prove, but it would be a potentially explosive finding, as Technology Review explains.

In quantum entanglement, two objects are connected by an invisible wave, like an umbilical cord, that allows them to essentially share the same existence. When something happens to one object, it immediately happens to the other, no matter how far apart they are.

Elisabeth Rieper and colleagues at the National University of Singapore say this entanglement might prevent the DNA double helix from shaking itself apart.

Technology Review's blog provides a nice description of some complex physics. Here's a breakdown:

Rieper and colleagues used a theoretical model of DNA in which each nucleotide consists of electrons orbiting a positively charged nucleus. The movement of the negative cloud is a harmonic oscillator.

When the nucleotides bond to form a base pair, the clouds must oscillate in opposite directions or the structure won't be stable. Rieper and colleagues asked what would happen to those oscillations when the base pairs are stacked in a double helix.

The helix should vibrate and fall apart, but it doesn't. Rieper and co. say this is because the oscillations occur as a superposition of states -- meaning they oscillate in all possible states at once. That effectively holds it all together.

The question is how to prove all this, as Tech Review notes. Rieper and co. say that in a standard analysis, there's not enough energy to hold DNA together, but their quantum theory makes it work. Still, that's not enough experimental evidence to prove that biology, too, is really just physics.

[Technology Review]

In one paper, researchers describe a "molecular spider" designed to perform a particular task, in this case walking along a certain, pre-programmed path. While traditional robots would rely on internal memory and processing to orient themselves toward their programmed goals, this spider gathers its commands from an environment that has been precisely defined by the researchers beforehand via nucleotides placed exactly where they want the spider to step.

A specially designed two-dimensional DNA origami landscape dictates the spider's movements. The spider is made of an inert molecule body and three catalytic legs adapted from a specific DNA enzyme that binds to certain nucleotides. When they do so, they cleave the nucleotides into two smaller ones with weaker attractions, at which point the leg moves on to the next strong bonding nucleotide. Moving independently of one another, the legs will carry the spider along a preset path laid out by the researchers, one step at a time, making turns and following the proper nucleotide until a set of uncleavable nucleotides makes it stop.

Pretty cool, but can we make it actually do something? A second paper says we absolutely can. Using a similar DNA origami tile, three DNA controlled two-state "DNA machines" and a DNA walker like the molecular spider above (with four feet and three "hands" that carry cargo), researchers aimed to show that by integrating several simple nanobots, we can create more complex nanosystems that can actually build things.

Each DNA machine holds a different gold nanoparticle, which it will either hold onto or let go of depending on whether it receives an "on" or an "off" command from its DNA programming. As the walker traverses the tile, the machines either pass off their cargoes or they do not. Which means at the end of the line, the finished product can be one of eight different products assembled from the gold nanoparticles, depending on which particles were handed to the walker.

Do that over and over, and you've got an assembly line. Not only that, but a machine can be manipulated to produce different end results depending on DNA commands, making it as versatile, in theory, as a computer controlled macro scale assembly line.

This is an oversimplification of course. The science behind all this is complicated and not easy to duplicate, but both papers express exciting new methods to manipulate things at the nanoscale in ways that were once the realm of fantasy (think The Magic School Bus or Fantastic Voyage). While widespread application is still a ways out, the idea of very, very small things programmed to assemble even smaller things tailored to our precise designs is very cool science indeed.