ENCODE and fighting about junk.

I recommend this post by Brendan Maher on Nature News about the ENCODE blowback.

Fighting about ENCODE and junk

Some comments:

1) It’s pretty clear that the evidence suggests actual biological function (in any reasonable meaning of that term) for 20%, and even that is an extrapolation. 80% is the figure only if your definition is so loose as to be all but meaningless.

Operationally, we define a functional element as a discrete genome segment that encodes a defined product (for example, protein or non-coding RNA) or displays a reproducible biochemical signature (for example, protein binding, or a specific chromatin structure).

In other words, a chunk of DNA is considered functional if is transcribed OR it is reasonably close to a protein-binding site OR it has some histone modification or other chromatin structure to it AND this only needs to be observed in one cell type. Seriously, the ENCODE definition of “functional” really is little more than a step up from “anything to which DNA polymerase can bind”.

2) Ewan Birney indicates, both in discussion with Maher and on his own blog, that he struggled with the decision to include the 80% figure. Perhaps there was pressure from the journal, colleagues, funding agencies, whatever. Well, too bad. He’s the lead author, and ultimately he is responsible for what is claimed in the paper. Not to mention that there is some further bluster reported in the media, like this from Ed Yong’s blog:

And what’s in the remaining 20 percent? Possibly not junk either, according to Ewan Birney, the project’s Lead Analysis Coordinator and self-described “cat-herder-in-chief”. He explains that ENCODE only (!) looked at 147 types of cells, and the human body has a few thousand. A given part of the genome might control a gene in one cell type, but not others. If every cell is included, functions may emerge for the phantom proportion. “It’s likely that 80 percent will go to 100 percent,” says Birney. “We don’t really have any large chunks of redundant DNA. This metaphor of junk isn’t that useful.”

So which is it? Does Birney go with the 20% figure that his data indicate, or the 80% — or even 100% — figure he has given in the ENCODE paper and in interviews?

3) Sure, there’s lots of interesting stuff to learn from the ENCODE project. Was it worth $185 million? I don’t know. I do know that what everyone is focused on is the “80% functional” claim, because that’s what it says in the abstract of the main paper and it’s what the media has been reporting everywhere. That, for sure, is a lemon.

4) Onion test.


1 comment to ENCODE and fighting about junk.

  • The Other Jim

    I think your point 3 is the real issue. The continued support of ENCODE relied on some big payback for the large investment. And now they have supplied the splash by their obscure definition of function. I fear the inclusion of the 80% number is purely political, and done to keep the cash rolling in.

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