Computational feat speeds finding of genes to milliseconds instead of years • Hacker News Board

Re: Computational feat speeds finding of genes to milliseconds instead of years

#11

Post by carbocation » Thu, Apr 08, 2010, 4:46 AM UTC

thisisnotmyname wrote: post #8

Tycho wrote: post #2

So in terms of curing cancer... where does this get us? (i'm not being sarcastic. it sounds very promising but I don't know enough on the topic to judge how significant it is)

First of all, don't ever trust a popular science writeup from the school of the corresponding author. It is almost certainly meaningless hype. Secondly, PNAS is a good journal, but not a great one. He was almost certainly rejected from the top tier. (Nature, Science) As someone who works in this field, finding genes that are similar in some way to two disease related genes is not at all novel. This is the goal of lit…

I agree that this paper is a run-of-the-mill systems biology paper. "Give me some genes, and I'll give you a network of genes that are associated via (insert functional method here)." Everyone does this. Unlike other methods that look at more than just expression... well, this just looks at expression.

A key question here is how many other pathways did they try this on before they got it to "work" on 10/14 (though really 10/60) B-cell-associated genes? I'm not asserting that they mined for the most favorable pathway, but I will say that this one example comes across as more of an anecdote than a proof of concept.

People are going to be using this tool perhaps hundreds of thousands of times. Don't show me one example where 10/14 genes "validated." Show me 20 examples where X out of N genes validate - if that's sufficiently high, I'll be much more interested.

Even the developmental focus of this new tool is fairly common practice by those in the field. Look at the Seidman lab or the Walsh lab at Boston Children's to see examples of other people thinking deeply about how developmental biology ties back into adult pathology.

Re: Computational feat speeds finding of genes to milliseconds instead of years

#12

Post by seshagiric » Thu, Apr 08, 2010, 4:58 AM UTC

I started off thinking it was another gpgpu application but the theory of boolean implications is something new to learn. thanks for the article.

Re: Computational feat speeds finding of genes to milliseconds instead of years

#13

Post by carbocation » Thu, Apr 08, 2010, 5:04 AM UTC

[deleted] wrote: post #10

[deleted]

It seems to me that the number of possible connections between genes should be (16000 genes * 16000 possible gene-gene interactions per gene) = 2.6 * 10^8. Why do you say 3 * 10^5?

Also, while a 14% FDR seems pretty good, it's just from one sample. I would like to have seen them repeat this procedure on (random) different pathways so we could see how variable the FDR might be.

Finally, I don't know how much this is truly enriched for B-cell genes as compared to a randomly seeded query. I'd like to see them compare their results to what they'd get if they had seeded their query with 2 random genes. Perhaps you could build a story about the association between a large fraction of all genes and B-cell development...

In short, this seems inadequately controlled.

Re: Computational feat speeds finding of genes to milliseconds instead of years

#14

Post by carbocation » Thu, Apr 08, 2010, 5:07 AM UTC

selflessGene wrote: post #6

Tycho wrote: post #2

So in terms of curing cancer... where does this get us? (i'm not being sarcastic. it sounds very promising but I don't know enough on the topic to judge how significant it is)

Could be fairly significant. One of the problems with biology is that we have a lot of data in terms of experimental tests, but we don't know all the data mean. Only a relatively small amount of the 30,000 human genes are clearly understood. And when you THINK you understand what it does, these genes can sometimes surprise by having other unexpected effects. What his method seems to do, is to help map out what genes…

A small quibble: there are more like ~18,000 genes in the human genome.

Re: Computational feat speeds finding of genes to milliseconds instead of years

#15

Post by aposteriori » Thu, Apr 08, 2010, 5:55 AM UTC

thisisnotmyname wrote: post #8

Tycho wrote: post #2

So in terms of curing cancer... where does this get us? (i'm not being sarcastic. it sounds very promising but I don't know enough on the topic to judge how significant it is)

First of all, don't ever trust a popular science writeup from the school of the corresponding author. It is almost certainly meaningless hype. Secondly, PNAS is a good journal, but not a great one. He was almost certainly rejected from the top tier. (Nature, Science) As someone who works in this field, finding genes that are similar in some way to two disease related genes is not at all novel. This is the goal of lit…

Regarding who submitted it, PNAS works differently from other journals. Weissman is a member of the National Academy of Sciences, and as such he gets to contribute a paper X times a year. It still gets peer reviewed. The question of how well things are reviewed applies to other journals as well.

Re: Computational feat speeds finding of genes to milliseconds instead of years

#16

Post by rflrob » Thu, Apr 08, 2010, 6:23 AM UTC

aposteriori wrote: post #15

thisisnotmyname wrote: post #8

Earlier quoted context omitted.

First of all, don't ever trust a popular science writeup from the school of the corresponding author. It is almost certainly meaningless hype. Secondly, PNAS is a good journal, but not a great one. He was almost certainly rejected from the top tier. (Nature, Science) As someone who works in this field, finding genes that are similar in some way to two disease related genes is not at all novel. This is the goal of lit…

Regarding who submitted it, PNAS works differently from other journals. Weissman is a member of the National Academy of Sciences, and as such he gets to contribute a paper X times a year. It still gets peer reviewed. The question of how well things are reviewed applies to other journals as well.

There's also the process of "communicating" papers. In those, a NAS member can essentially vouch for other authors twice a year, and provide outside reviewers of their choice. This track is ending as an option this July, however.

Re: Computational feat speeds finding of genes to milliseconds instead of years

#17

Post by [deleted] » Thu, Apr 08, 2010, 6:38 AM UTC

carbocation wrote: post #13

[deleted] wrote: post #10

[deleted]

It seems to me that the number of possible connections between genes should be (16000 genes * 16000 possible gene-gene interactions per gene) = 2.6 * 10^8. Why do you say 3 * 10^5? Also, while a 14% FDR seems pretty good, it's just from one sample. I would like to have seen them repeat this procedure on (random) different pathways so we could see how variable the FDR might be. Finally, I don't know how much this is t…

[deleted]

Re: Computational feat speeds finding of genes to milliseconds instead of years

#18

Post by Estragon » Thu, Apr 08, 2010, 12:40 PM UTC

With this kind of thing, the devil is always in the details. He's looking for genes whose expression levels correlate with those of genes known to be involved in the process of interest. This is not a new idea. The trouble is that spurious correlations can arise in all kinds of surprising ways, and swamp the interesting ones.