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Wednesday, February 27, 2013

ENCODE - All about "Functions"

Contributed by: Jianzhi Zhang

In 2012, the 288-million-dollar ENCyclopedia Of DNA Elements (ENCODE) project concluded in its 442-author Nature article that 80% of the human genome are functional. The completion of this massive study was regarded by both Nature and Science as one of the most important scientific accomplishments of the year. But are these 442 scientists correct?
Dan Graur and five colleagues have now analyzed the ENCODE paper. Their conclusion is shocking, to say the least. They found that the ENCODE conclusion was erroneous and was reached mainly “(1) by employing the seldom used “causal role” definition of biological function and then applying it inconsistently to different biochemical properties, (2) by committing a logical fallacy known as “affirming the consequent,” (3) by failing to appreciate the crucial difference between “junk DNA” and “garbage DNA,” (4) by using analytical methods that yield biased errors and inflate estimates of functionality, (5) by favoring statistical sensitivity over specificity, and (6) by emphasizing statistical significance rather than the magnitude of the effect”. The number and seriousness of the errors and inconsistencies they identified from the ENCODE paper are horrifying. One cannot help but wonder where the reviewers of the ENCODE project/paper were and what the 288 million dollars would accomplish if used to fund 200 NIH R01 grants.
I recommend Graur et al.’s paper to all biologists, evolutionary or not, because it deals with some of the most fundamental concepts in biology with unusual clarity and wit. It also prompts one to ponder on the pros and cons of big science vs. small science. Last but not least, if you are intelligent, you will enjoy reading this 43-page PDF.

The ENCODE Project Consortium. 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57-74. 
Graur, D., Zheng, Y., Price, N., Azevedo, R. B. R., Zufall1 R. A., and Elhaik E. 2013. On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE. Genome Biol. Evol., published February 20, 2013, doi:10.1093/gbe/evt028

1 comment:

  1. It was easy to catch that the definition of 'function' in the ENCODE papers is not what one would normally use, and multiple bloggers have criticized it. But after reading the Graur et al's paper, what really shocked me was the data analysis part of the ENCODE paper. It was Dan's wit that saved me from being panicked.