The ENCODE Data Dump and the Responsibility of Scientists

A few hours ago I criticized science journalists for getting suckered by the hype surrounding the publication of 30 papers from the ENCODE Consortium on the function of the human genome [The ENCODE Data Dump and the Responsibility of Science Journalists].

They got their information from supposedly reputable scientists but that's not an excuse. It is the duty and responsibility of science journalists to be skeptical of what scientists say about their own work. In this particular case, the scientists are saying the same things that were thoroughly criticized in 2007 when the preliminary results were published.

I'm not letting the science journalists off the hook but I reserve my harshest criticism for the scientists, especially Ewan Birney who is the lead analysis coordinator for the project and who has taken on the role as spokesperson for the consortium. Unless other members of the consortium speak out, I'll assume they agree with Ewan Birney. They bear the same responsibility for what has happened.

Ewan Birney is listed as the corresponding author for the main summary paper in Nature: An integrated encyclopedia of DNA elements in the human genome. Here's the opening paragraph,

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

I've highlighted the main take-home message.

The papers show no such thing as Ewan Birney admits on his own blog [ENCODE: My own thoughts].

It’s clear that 80% of the genome has a specific biochemical activity – whatever that might be. This question hinges on the word “functional” so let’s try to tackle this first. Like many English language words, “functional” is a very useful but context-dependent word. Does a “functional element” in the genome mean something that changes a biochemical property of the cell (i.e., if the sequence was not here, the biochemistry would be different) or is it something that changes a phenotypically observable trait that affects the whole organism? At their limits (considering all the biochemical activities being a phenotype), these two definitions merge. Having spent a long time thinking about and discussing this, not a single definition of “functional” works for all conversations. We have to be precise about the context. Pragmatically, in ENCODE we define our criteria as “specific biochemical activity” – for example, an assay that identifies a series of bases. This is not the entire genome (so, for example, things like “having a phosphodiester bond” would not qualify). We then subset this into different classes of assay; in decreasing order of coverage these are: RNA, “broad” histone modifications, “narrow” histone modifications, DNaseI hypersensitive sites, Transcription Factor ChIP-seq peaks, DNaseI Footprints, Transcription Factor bound motifs, and finally Exons.

In other words, "functional" simply means a little bit of DNA that's been identified in an assay of some sort or another.

For someone who claims to have "spent a long time thinking about and discussing this" that's a remarkably silly definition of function and if you're using it to discount junk DNA it's downright disingenuous. Did Birney really not anticipate all the hype about refuting junk DNA? Come on, he can't have been that stupid, could he?

Here's the video he prepared with Magdalena Skipper, Senior Editor at Nature. Check out what she says at 2:28

The striking overall result that the ENCODE project reports is that they can assign a function, a biochemical function, to 80% of the human genome. The reason why this is striking is because, not such a long time ago, we still considered that the vast proportion of the human genome was simply junk because we know that it's only 3% that encodes proteins.

Where did she get that idea if not from Ewan Birney? Watch Birney's performance to see if he challenges this interpretation or supports the concept that most of the human genome is involved in a vast network of complex controls.


Scientist have a responsibility to be scrupulously accurate when they present their own work to the general public. That means they should recognize the difference between what the data actually says and their own interpretation of the data. When scientists know that there are other ways to interpret the data, they are obliged to mention that. That's the mark of a good scientist. In this case Birney is well aware of the controversy over interpreting pervasive transcription and the possible insignificance of a DNA binding site. He knows that because the ENCODE Consortium was challenged in 2007 when it presented the results of the pilot project (see The ENCODE Data Dump and the Responsibility of Science Journalists).

This is, unfortunately, another case of a scientist acting irresponsibly by distorting the importance and the significance of the data. It's getting to be a serious problem and it makes it hard to convey real science to the general public. The public now believes that the concept of junk DNA has been rejected by scientists and that our huge genome really is full of wonderful sophisticated control elements regulating the expression of every gene.

It's going to take a lot of effort to undo the damage caused by scientists like Ean Birney.

---