What a difference two years make! The styles of ENCODE 2012 and ENCODE 2014 are completely different.
Gone are the pretensions that every biochemical peep is a “function.” Gone are the unqualified proclamations and the pompous certainty. If anything, the caution exhibited by ENCODE 2014 is excessive. I’ll soon be unemployed.
In the commentary and the five Nature articles, every statement is measured, unknowns are acknowledged, and caveats abound. The fresh air permeating the ENCODE 2014 articles is dizzying. I have never been exposed to so much oxygen.
“Although the function of these regions has not been assessed, our work in Drosophila suggests that many are active enhancers, which trigger gene transcription. However, because factors can bind DNA without functional consequences, especially at HOT regions, the contribution of each of the bound factors to enhancer activity remains unclear.”
Translation: Not every piece of chewing gum attached to the soles of your shoes is functional. Moreover, the function of the sole of your shoe to which the chewing gum stuck is NOT to bind chewing gum.
“Furthermore, although they are extremely data-rich, the papers expose how data sets that are created to catalogue all functional elements under standardized conditions are not sufficient for understanding the regulation of transcription, chromatin biology and enhancer function, nor the evolution of these mechanisms.”
Translation: We report on a zillion experiments, each of which could have been performed differently. Thus, ENCODE studies cannot tell us anything about biological function.
“Addressing such questions typically requires more-diverse set-ups and experiments, often specifically adjusted for each question. In addition, the identification of regulatory elements remains limited by the lack of cell-type specificity and the fact that chromatin features and regulatory-factor binding are imperfect predictors of regulatory-element function.”
Translation: Big Science is useless in elucidating function. Only Small Science and hypothesis driven science will be able to provide us with insight.
“The papers do not reveal how many of these elements might be functional, and independent estimates span a broad range.”
Translation: The proclamations by ENCODE 2012 were complete and utter bullshit and the nasty criticism has touched our sensitive souls. We are not going to repeat these errors in 2014.
Members of the ENCODE consortium practicing self flagellation prior to the publication of the 2014 batch of articles