What do you think about the argument put forward by Graur et al (2013) in their article titled: On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE (Genome Biol Evol (2013) doi: 10.1093/gbe/evt028)?
I agree with them that some of the statistics in ENCODE could be over estimates and that most genomic studies should include an evolutionary component when describing function.
I find the discussion on the transcription factors binding sites is lacking information and I am not sure they compare similar experiments that can be compared. They also have a strong view on definitions but do not define a "normal transcription factor". I don't think this is an accurate description of transcription factors as each is its own protein with its own binding properties.
I would be interested to hear your opinion as this paper has sparked a strong debate in our research group.
I've just read the paper, and I think the authors criticism of ENCODE is highly misplaced.
The message of the ENCODE papers are really not about whether 80% or 10% of the genome ar "functional" or not (whatever definition of "function" you might appreciate), but to show that what is happening on the genome in terms of chromatin modifications, TF-binding and transcription is not restricted to conserved elements or protein coding genes. A lot of things are happening which are clearly measurable, and this surely needs to be reported rather than ignored due to "lack of conservation". I think ENCODE have made a good job in trying to make sense of all this information.
I regularly work with ENCODE data (but I'm not a part of ENCODE project), and have read many of the ENCODE papers, and generally their conclusions fit with my own observations in the data.
Actually I often have a much harder time understanding the logics behind the criticism by Graur et al., than the logic behind the analysis in ENCODE. Especially in the sections criticising analysis on TF and histone modifications, it seems to me that their criticism is due to lack of understanding of the basic principles in both methodology and analysis used. I agree with carlo Cossano above:
"The evidence that is mounting, though, reveals another "story""
Those "big science" studies are overvalued and I am glad critical voices appear. The main problem is that they are sloppy and add a lot of noise and false data that needs a lot of further effort to clean up. The ENCODE was a sad waste of resources in my view.
And here more criticism for the hyped ENCODE:
http://blog.openhelix.eu/?p=13656
That paper by Graur et al is really interesting.
Scientifically, I think most of their arguments in this GBE paper are valid. Put aside the evolutionary criteria, what could be ENCODE's answer to the question "why transcription is considered functional while replication is not?"
Although their data could be useful, the biases in it would remain as a problem to many application of the data.
I just wish the distribution of resource for scientific research is not so biased by such hype.
Hallo! I found the style of the paper a bit arrogant, for instance in sentences such as “… it would be RIDICULOUS to assume that 70+% of the human genome consists of elements under undetectable selection…”. This is not the best way to trigger a discussion in the scientific community, even if absolutely interesting and worth to be considered under several points of view.
Concerning the overall paper, I think we have still not enough tools and knowledge to fully judge the functional role of different parts of the genome, and thus to fully detect/measure the level of selection on them. For instance, it might be possible that selection is not merely acting on single nucleotide substitutions but on other general properties of the DNA molecule: eg: chemico-physical properties linked to environmental or body temperature, or else on not yet identified motifs/properties influencing the binding of DNA portions to the nuclear lamina, and so on…
Thus, in view of all these not yet clarified issues, I would be more cautious in drawing so peremptory conclusions. This is of course my modest opinion. ;-)
The paper, that honestly I've not read completely, has some kind of ideological philosophy flavour..
The evidence that is mounting, though, reveals another "story".
Just for an example quite recent:
http://www.sciencedaily.com/releases/2013/02/130217134240.htm
I've just read the paper, and I think the authors criticism of ENCODE is highly misplaced.
The message of the ENCODE papers are really not about whether 80% or 10% of the genome ar "functional" or not (whatever definition of "function" you might appreciate), but to show that what is happening on the genome in terms of chromatin modifications, TF-binding and transcription is not restricted to conserved elements or protein coding genes. A lot of things are happening which are clearly measurable, and this surely needs to be reported rather than ignored due to "lack of conservation". I think ENCODE have made a good job in trying to make sense of all this information.
I regularly work with ENCODE data (but I'm not a part of ENCODE project), and have read many of the ENCODE papers, and generally their conclusions fit with my own observations in the data.
Actually I often have a much harder time understanding the logics behind the criticism by Graur et al., than the logic behind the analysis in ENCODE. Especially in the sections criticising analysis on TF and histone modifications, it seems to me that their criticism is due to lack of understanding of the basic principles in both methodology and analysis used. I agree with carlo Cossano above:
"The evidence that is mounting, though, reveals another "story""
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