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Free Program Predicts How Troublesome a Genetic Mutation Is

samzenpus posted more than 2 years ago | from the giant-misprinted-book-that's-hidden-inside-you dept.

Science 34

smoothjazz writes "Researchers describe a new, freely available Web-based program called Spliceman for predicting whether genetic mutations are likely to disrupt the splicing of messenger RNA, potentially leading to disease. From the article: 'Spliceman makes its predictions about mutations by calculating that distance. It has successfully predicted the known effect of many mutations. The software has genomic information about 11 species: humans, chimpanzees, rhesus monkeys, mice, rats, dogs, cats, chickens, guinea pigs, frogs, and zebra fish.'"

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34 comments

ha! (0)

Anonymous Coward | more than 2 years ago | (#39250551)

So can this explain why my parents are so stupid?

Re:ha! (1, Funny)

Anonymous Coward | more than 2 years ago | (#39251061)

So can this explain why my parents are so stupid?

I see that at least these genes were passed faithfully.

Gamemaker! (-1)

Anonymous Coward | more than 2 years ago | (#39250565)

Switch to Gamemaker to fix these problems!

Amateur scientists, amateur scientists! I can't even stand it anymore! These scientists don't want to use Gamemaker because then everything would change!

Scientists are unreliable; they're always changing their minds!

Re:Gamemaker! (1)

ackthpt (218170) | more than 2 years ago | (#39250705)

Switch to Crowdsourcing to fix these problems!

Amateur scientists, amateur scientists! I can't even stand it anymore! These scientists don't want to use Crowdsourcing because then everything would change!

Scientists are unreliable; they're always changing their minds!

Shhh. Don't tell them it's a g-a-m-e. More fun this way. Also, if patents are involved and someone's profiting from the crowd's work, then it's helping Wall Street ;-)

Inbreeding (5, Funny)

j. andrew rogers (774820) | more than 2 years ago | (#39250647)

This app is part of the sex education class in Arkansas!

static code analysis tool (4, Interesting)

vlm (69642) | more than 2 years ago | (#39250669)

Rephrased, its a static code analysis tool for mRNA

http://en.wikipedia.org/wiki/List_of_tools_for_static_code_analysis [wikipedia.org]

Now taking bets on 10:1 odds that after posting this, some joker adds spliceman to the wiki page. Frankly it probably does belong there.

Yes, I am one of "those guys" who trys to make my perl scripts Perl::Critic compliant, in addition to running them thru perltidy. The closest thing I know of for Ruby is "laser" and I don't know a good reformatting tool for Ruby.

Re:static code analysis tool (3, Interesting)

Samantha Wright (1324923) | more than 2 years ago | (#39251241)

That's the idea. Of course, mRNA splicing sites are way harder to find than blocks of code (the sequence is described probabilistically, in essence), and it's subtly different between species. Fortunately it's not even remotely Turing-complete; it's closer to a context-free grammar, on the level of parenthesis matching. Which is evaluated in a probabilistic order. With Turing-complete compiler macros. (It's true: all living organisms are secretly written in PL/I.)

So let's make this a Game! (1)

ackthpt (218170) | more than 2 years ago | (#39250671)

Call it Mutant Madness, try to find the most troublesome mutant genes, which are indifferent or compatible with other mutations and award skills, points, ...

Mmmm. Sounds too much like my massive collection of Crazy Bones. Nemminds.

Re:So let's make this a Game! (2)

Samantha Wright (1324923) | more than 2 years ago | (#39251505)

Humans aren't very good at the problem of RNA splice site finding, unfortunately. Like Reversi/Othello, it involves detecting a large number of subtle changes in closely-related states that have dramatic downstream effects. The game would consist primarily of looking at a bunch of roughly hill-shaped graphs and trying to determine which ones cross certain thresholds or most closely resemble certain other curves. Computationally those are pretty manageable tasks.

Superpowers (0, Interesting)

Anonymous Coward | more than 2 years ago | (#39250681)

How long does the simulation have to run before it predicts super powers?

Re:Superpowers (2)

Samantha Wright (1324923) | more than 2 years ago | (#39251547)

It's not really a simulation; it just tells you if a given sequence appears to resemble a splice site, and the probability that the single-nucleotide mutation specified by the user will alter that site's tendency to splice. Not a new accomplishment in biology by any means; the headline is sadly and totally overblown.

Paging Professor Xavier (2, Funny)

sehlat (180760) | more than 2 years ago | (#39250739)

This sounds like a great tool for predicting the abilities of new recruits.

Nothing new here. (0)

Anonymous Coward | more than 2 years ago | (#39250863)

So, this is just like MutationTaster, SIFT, Polyphen 2 et. al. in that it's a free algorithm for predicting how deleterious a mutation is?

Oh, it only uses RefSeq sequences, rather than letting you specify a transcript set.

Don't get me wrong, I'm sure it's perfectly adequate. But it's just one of many pieces of software that do a similar thing.

Re:Nothing new here. (1)

Samantha Wright (1324923) | more than 2 years ago | (#39251657)

Of course it only uses RefSeq! Don't you remember what your third-year professors taught you about the uncurated GenBank pool? Wikipedia users and terrorists post in there!

...actually, I'm pretty sure the only usage of RefSeq data is to establish the correct profile of what a splice site should look like. You can still feed it any FASTA sequence.

It's begun (-1)

Anonymous Coward | more than 2 years ago | (#39250881)

The bio revolution is starting. Theoretical understanding of life. All you space loons with your decades-old nostalgia for test pilots in tin cans, watch out. You're as irrelevant as a vacuum tube computer, you will be flattened by the bio age. Eccentric billionaires still spending money on vanity space projects? Losers.

Re:It's begun (2)

0123456 (636235) | more than 2 years ago | (#39250957)

Back in the real world, the 'bio age' will be another incentive to get the hell off this planet before someone wipes us out with an engineered disease. I'm sure the 'humans are a cancer' Greenists are just salivating at the thought.

Re:It's begun (1)

Samantha Wright (1324923) | more than 2 years ago | (#39251685)

Nope. Not this story. Come back in five years, maybe. This is just an incrementally better method of doing a test we've had computers doing since the early nineties... and that we've been doing by hand for (close to) twice that period of time.

Ruined by stupid PR (5, Informative)

pesho (843750) | more than 2 years ago | (#39251139)

Free Program Predicts How Troublesome a Genetic Mutation Is

No it doesn't.

This is yet another case of how stupid PR does damage to otherwise good science. The original paper [pnas.org] (not the PR release) describes a statistical model. The model tells you how likely it is for a mutation to affect splicing. According to ROC curve on figure 4 it isn't nearly as selective or sensitive as you need it to be for any clinical application. It is however a great research tool. The PR article makes another false assumption, by stating that mutations affecting the splicing of an exon invariably cause 'trouble'. In fact it is well established that there is a significant variability in exon usage in perfectly healthy humans (citations below).

1. Kwan, Tony, David Benovoy, Christel Dias, Scott Gurd, David Serre, Harry Zuzan, Tyson A. Clark, et al. “Heritability of Alternative Splicing in the Human Genome.” Genome Res. 17, no. 8 (August 1, 2007): 1210–1218.
2. Zhang, Wei, Shiwei Duan, Emily O. Kistner, Wasim K. Bleibel, R. Stephanie Huang, Tyson A. Clark, Tina X. Chen, et al. “Evaluation of Genetic Variation Contributing to Differences in Gene Expression Between Populations.” The American Journal of Human Genetics 82, no. 3 (March 3, 2008): 631–640.

Re:Ruined by stupid PR (3)

zebslash (1107957) | more than 2 years ago | (#39251259)

As a geneticist, I completely agree. Furthermore, there are mutations that are particularly "troublesome" or completely lethal without affecting splicing! For instance, some muscular distrophies are caused by a single amino-acid replacement in a protein.

Re:Ruined by stupid PR (0)

Anonymous Coward | more than 2 years ago | (#39255331)

Science, smience. This software makes mutants. Hook it up to a 3D printer and I will have my mutant army.

Re:Ruined by stupid PR (0)

Anonymous Coward | more than 2 years ago | (#39259853)

Free Program Predicts How Troublesome a Genetic Mutation Is

No it doesn't.

And... no it isn't either. It's free as in proprietary... wonderful slashdot journalism indeed.

Interesting, But Not The First (2, Informative)

Anonymous Coward | more than 2 years ago | (#39251169)

This is an interesting program, but it's hardly the first (coming from a grad student in Bioinformatics studying variation in the cancer genome). There are a large number of programs attempting to determine the impact of variation in the genome. We use these in our work with the exome (enrichment and sequencing of just the known coding elements in the human genome). A much larger challenge is finding true positive base and indel variation from next-generation sequencing, where alignment and sequencing artifacts lead to many false positive signals.

Here are two of the most popular:
SiFT: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC168916/
PolyPhen: http://www.ncbi.nlm.nih.gov/pubmed/12202775?dopt=Abstract

-Lee

The Flu and The Oil Light (0)

Anonymous Coward | more than 2 years ago | (#39251213)

not to mention no robot to do the dishes, vacuum the radiation, trash, etc, etc.

and that oil light

still not fixed

were we not promised jet packs by now?

free program sucks dick (0)

Anonymous Coward | more than 2 years ago | (#39251341)

at least that would be an interesting article

mod d0wN (-1, Troll)

Anonymous Coward | more than 2 years ago | (#39251669)

any parting shot, discussions on 0f HIV and other show that FreeBSD

Test result: You are Magneto (0)

Anonymous Coward | more than 2 years ago | (#39256815)

(this is very troubling)

Make it phone based (0)

Anonymous Coward | more than 2 years ago | (#39258051)

Welcome to DNA Evaluator! To start, are you a:

Press or say: one for monkey, two for zebrafish, three for human, four for chimpanz-

Four!

Thank you! Please enter your DNA using your touch-tone phone's keypad. If you are not using a touch-tone phone, please stay on the line and an operator will assist you shortly. ///Many years later

Thank you for using our services! The DNA has been entered into the system. Please wait a moment for the results.

We're sorry, the DNA you entered is not correct. Please re-enter your DNA. You have four attempts remaining, before you must alter your DNA.

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