A Beautiful Mind

Ive spent the past week staring at a computer screen, comparing amino acid sequences of the envelope gene of various kinds of HIV-1.

CNNKTFNGTGPCHNVSTVQCTHGIKPVVSTQLLLNGSLAEREIIIRSENLTDNVKTIIVHLNESVEISCTR
PNNNTRKSIRIGPGQAFYATGDIIGDIRQAHCNISENWNKTLEWVRKKLEEHFPNKTIAFKPSSGGDLEI
TTHSFNCRGEFFYCNTSKLFNGTDN

CNNKTFNRTGPCNNVSTVQCTHRIKPVVSTQLLLNGSLAERKIIIRSKNLTDNVKTIIVHLNESVKIECTR
PNNNTRQSTKIRPGQVFYAISNIIGDIRQAHCTINKKEWNTTLQQVTEKLKEHFPNKTIAFQPSSGEDLEI
TTHSFNCKREFFYCNTSKLFNSTDN

CNNKTFNRTGPCNNVSTVQCTHRIKPVVSTQLLLNGSLAERKIIIRSENLTDNVKTIIVHLNESVEINCTR
PNNNTRKSIRIGPGQAFYATGDIIGDIRQAHCNISKENWNKTLQWVKEKLEEHFPNKTIVFKPSSGGDLEI
TTHSFNCRGEFFYCNTSKLFNSTDN

CNNKTFNRTGPC…

Im just looking for changes and patterns (hey that glycosylation site disappeared! oh, all the sequences that dont process gp160–>gp120/gp41 lack that glutamic acid! etc).

Its kinda like a bizarre word search…

Unfortunately, Ive been at this for too long. Im starting to see patterns and connections everywhere, a la John Forbes Nash. Im creeping myself out.

For instance, I figured out why I find Craig Venter irresistible.

Its a well known fact that I like smart people. But most of the time, when it comes to my elders, its just a ‘Oh my god I want to eat your brain‘ sort of attraction.

Venter is different. Sure hes rich and a bad boy and a genius, but I recognize the fact that he is an older, balding male, and I shouldnt find him attractive… but I do.

I figured out why!

OF COURSE! NOW IT MAKES SENSE!

Also, Im starting to think Seth MacFarlane is some sort of time-traveling alien trying to communicate with me via Family Guy. Oh hahahaha it was funny when he perfectly described my dating life (Im Brian), but then I saw THIS on an old episode from earlier this year:

WHAT THE FUCK?

To make matters worse, you know the guy who threw his shoes at Bush? An event so random and hysterical it could have been on Family Guy? Look at this pic:

Who is that in the lower right? Who is it???

PETER GRIFFIN.

… Im going to go drink a beer.

Comments

#1 Blake Stacey
December 15, 2008

Working on my undergraduate thesis involved quite a bit of staring at columns of fluctuating numbers (I was analysing data using a genetic algorithm). My friend Eric caught me looking at such a display and said that I was one step away from becoming the guy from the movie Pi.
#2 ERV
December 15, 2008

Sometimes I pretend Im reading The Matrix.
#3 Tyler DiPietro
December 15, 2008

“oh, all the sequences that dont process gp160–>gp120/gp41 lack that glutamic acid!”

To my CS oriented mind, that looks sort of like eval. Am I even close?
#4 Tyler DiPietro
December 15, 2008

By the way I just accidentally a PCR machine. Is this bad?
#5 Lledowyn
December 15, 2008

How come you’re staring at the letter soup instead of having a computer do the comparisons for you? I can definitely see how you can become loopy if you’re doing it with your eyes instead of having a computer do it. Any particular reason why you can’t just get a quickie string compare program do it for you?
#6 Becca
December 15, 2008

Venter is skeezy.
*inverse snobism*
People who wear rolexes on the covers of Time should not be permitted to call themselves scientists.
*/snobbery*
*actual legitimate disagreement with Venter’s entire philosophy*
Patenting the human genome my ass!
*/win*

Patrick Stewart is totally hot though.
#7 ERV
December 15, 2008

Oh I do have a computer compare them– but I need to compare them to each other one at a time. 1 to 2, 1 to 3, 1 to 4… Little differences in AA can mean big changes in Env structure/function.
#8 Tyler DiPietro
December 15, 2008

Becca, I don’t know whether you’re being serious or not, but as far as I know Venter has never intended to patent to human genome. He only intends to patent applications in synthetic biology.
#9 MattK
December 15, 2008

I’m very far removed from biotech, so I’m serious when I ask, what does this mean: “He only intends to patent applications in synthetic biology.” ?

Is this talking about patenting application X, application X to modify gene Y, or is it patenting doing anything to gene Y? Anyone should be able to do a test (or whatever) to gene Y unless someone else actually owns the patent for the test itself.

I’m sorry to say that my only education in this area comes from Crichton’s Next. If that it is not a gawdawful book full of crap then it is a loan outlier on an otherwise tight distribution of increasing crappiness culminating in State of Fear. So basically I am not informed about American biotech laws re. property rights.
#10 becca
December 15, 2008

Oh it’s total hyperbole. But if they’d had allowed him, he would have patented genes. His positions on intellectual property have sometimes been rather outrageous. Venter:biology ::Gates:computer science.
#11 Tyler DiPietro
December 15, 2008

“Is this talking about patenting application X, application X to modify gene Y, or is it patenting doing anything to gene Y?”

As far as I know, the first two are good approximations to synthetic biology patents. Though I also work from incomplete knowledge.
#12 Tyler DiPietro
December 15, 2008

Becca,

What’s a specific position of his that you would consider “outrageous”? I’m not aware of any attempt on his part to patent genes.
#13 becca
December 15, 2008

Note- that second statement should have read:
“But if they’d had allowed him, he would have patented genes by the truckload” (to answer MattK, I think he was *trying* to patent the gene in general, for no specific purpose but as a catch-all. It’s a tough sell).

Now he’s not trying to patent “applications” but the entirety of his “synthetic genome”.
#14 becca
December 15, 2008

Tyler- see http://news.bbc.co.uk/1/hi/sci/tech/487773.stm
It’s a little hard to find in Google given all the more recent times he’s been in the news.

If this (http://txtwriter.com/Onscience/Articles/genome.html) is to be believed, the HapMap we ended up with might have been pay-to-search. Which would totally suck for the molecular epidemiologists.
#15 Tyler DiPietro
December 15, 2008

“Now he’s not trying to patent “applications” but the entirety of his “synthetic genome”.”

Well, a synthetic genome would by definition be an application, would it not?
#16 Tyler DiPietro
December 15, 2008

I stand corrected on Venter and patenting genes, it appears he has attempted to do so.
#17 MattK
December 16, 2008

The article that becca linked to seems to suggest that these people are trying to patent actual genes. I’m suspicious that I’m missing a certain amount of nuance here (at least I hope so). It just seems preposterous and presumptuous to ‘claim ownership over a fact of nature’ (to paraphrase Crichton). Anyway, since I’m not an American, all I can do is hope that either a) the U.S. and A legal system comes to its senses or b) every other country (including mine) ignores these silly patents. I mean, I get the argument about profits driving innovation but I’m not swayed by it. Is it even correct? One could certainly make the counter argument that it stifles innovation by limiting research to one company and its paying customers. I feel it is beside the point anyway, since, as I said before, I think that it is a morally indefensible position. Additionally, I suffer from a profound distrust of the idea that unchecked capitalism is a force for good. Maybe Adam Smith should keep his ‘invisible hand’ to himself on this one.
#18 Bob O'H
December 16, 2008

MattK – you’re right, it was preposterous. Even earlier, there was a move by Venter to patent ESTs, which are short fragments of DNA from genes, even though they didn’t know what the sequences or the genes did. That almost derailed the Human Genome Project, because everyone else involved felt they had to patent too, to protect their work. Eventually good sense prevailed, although I can’t remember the details.
#19 kingjoebob
December 16, 2008

hmm… you are looking for something that is missing? if you know what you are looking for then a simple regex should tell you everything that has it and anything that doesn’t. Now if you need to look for something in a certain spot then you might have to chop up the string a bit… in grad school I wrote a progie to analyze dna sequences of some bacteria.. e.coli i think. its not that hard hell their might be one out there already for you to use.

send me an email if you want specifics

–
bobbers
#20 Stephen Wells
December 16, 2008

Abby, apparently your mind contains the most horrifying slash fiction concept ever. Please, keep it locked up in there
#21 Paul Lundgren
December 16, 2008

So tell us, Abby, when do you finally get to graduate and join the real world full-time?
#22 Sili
December 16, 2008

What? CP + #1?

If you find that to be “the most horrifying slash fiction concept ever”, you really haven’t looked very closely.

Interesting thought, though, that Venter should be their timetravelling spawn from the future.

Personally, I find the idea of an anthropomorphic dog having a girlfriend far more squicky.
#23 Bayesian Bouffant, FCD
December 16, 2008

Venter is different. Sure he’s rich and a bad boy and a genius,

All that is true and fine, but be aware he no longer likes to be called maverick, now that the term has been sullied.
#24 windy
December 16, 2008

“The article that becca linked to seems to suggest that these people are trying to patent actual genes.”

Trying? According to the recent SEED 18-22% of human genes have already been claimed as US intellectual property. But Venter’s hardly the main culprit.

“Anyone should be able to do a test (or whatever) to gene Y unless someone else actually owns the patent for the test itself.”

Look up the patents on BRCA1 or BRCA2, a company actually owns the right to tell you whether you have the breast cancer causing variants of these genes. Which is fucked up since the ‘test’ is just sequencing the gene.
#25 mo
December 16, 2008

Which alignmentprogram do you use? If you are comparing one sequence at a time, you probably don’t have a good one. I like this one:
http://www.jalview.org/index.html

You paste in everything in FASTA format, and in the new window with your sequences you choose Web Service -> alignment -> Muscle/MAFFT/ClustalW

ClustalW is bad because it compares only two sequences at a time and then it compares a sequencecombination made up from the last two with an other sequence, so it doesn’t always get the same results from same sequences, but the other two are good, they compare everything to each other, and MAFFT is also fast.

(the downside is that those multiple sequence alignment programs are webservices, so maybe you don’t want to use them because you are sending your sequences to the internet. If that worries you, get an offline msa program with your grants or ask the bioinformaticians at your university nicely)

then you get your sequences written over each other in rows, with the similar aminoacids in the same columns. you can check for conservation, the higher the bars in that column, the more conserved the aa. 100% identity gets a * in conservationvalue. You can also customize the colorcode, so that it shows you all the N/S/T in colors, if you are searching for glycosylationsites. You can even make a Neighbor Joining Tree in Jalview, a phylogenetic tree, though not in good quality and lacking statistical values. If you want to make a better tree, use this:
http://www.atgc-montpellier.fr/phyml/
for this program, you have to erase the parts of your sequences which contain gaps, and set a bootstrap value, which gives the branches statistical support. The output from Jalview has to be in phylip format, an easy to read textformat for alignments. Ask you PI or grap a book/bioinformatician to find out how it has to look like.
Sorry for my English. I’m also new to this stuff, but it’s fun to tweak around your sequences.
#26 MattK
December 16, 2008

wendy, you are not doing anything to allay my nagging suspicion that American industry is trying to get all colonial up in the genome. I wonder if Native North Americans, when pondering the arrogance of the Europeans (“how can a person claim to own land?”), felt as bewildered as I do now (“how can a person claim to own genetic information that they did not fucking invent?). Thankfully, my province sent a big fuck you to those presumptuous bastards. Clement is a chiropractor, and I was pretty incensed at his appointment as federal Industry Minister. Nevertheless, props where props are due. Unfortunately, proper disrespect of gene patents does not seem to be a continuing trend in Canuckland.

P.S. – Hey astronomers! I have a great scheme. The first group to find an asteroid or other celestial missile that is on a path that could plausibly lead to the obliteration of Earth should patent it. Then they should charge a hefty premium from anyone that wants to look at it or interact with it or alter its trajectory. Earthicans would pay through the nose for that shit.
#27 windy
December 16, 2008

wendy, you are not doing anything to allay my nagging suspicion that American industry is trying to get all colonial up in the genome.

Hm? I wasn’t trying to allay anything, I am pointing out that they already are all over the genome.

The case in Ontario is the same patent that has been going in and out of the European patent office. One of the narrowed down versions they submitted was that the patent would only cover detection of the mutation in Ashkenazi Jews – iow, only Ashkenazi Jews would have to pay for the test! WTF?
#28 MattK
December 16, 2008

Hm? I wasn’t trying to allay anything

I know, I was being sarcastic.

One of the narrowed down versions they submitted was that the patent would only cover detection of the mutation in Ashkenazi Jews – iow, only Ashkenazi Jews would have to pay for the test! WTF?

ha ha. FTW is right. I take it that they didn’t run that one by their PR droids.
#29 MattK
December 16, 2008

Uh, guess that would be windy, not wendy in number 26