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Was ENCODE’s Claim of 80% of Human Genome Being Functional all Hype?

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An interesting paper titled On the Immortality of Television Sets: “Function” in the Human Genome According to the Evolution-free Gospel of ENCODE came out in Genome Biology. Two sentences of abstract should tell you what it is all about.

The ENCODE results were predicted by one of its authors to necessitate the rewriting of textbooks. We agree, many textbooks dealing with marketing, mass-media hype, and public relations may well have to be rewritten.

We have not got a chance to go through the paper, but one name in the author’s list suggests that we should. Eran Elhaik was the author of a controversial study we posted few days back.

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Prior to posting that commentary, we searched through Haldane’s Sieve blog, which covers unusual arxiv-posted preprints on population biology. After not finding anything on Dr. Elhaik’s paper, we asked for opinion from one of the authors of Haldane’s Sieve and did not get any response. That forced us to do the hard work of going through both the original study of Behar et al. and Elhaik’s revised analysis and figure out who was correct. We found Dr. Elhaik’s numerical methods to be more accurate and they clearly backed his conclusions. Since then, we corresponded heavily over email with Dr. Elhaik and found him to be an excellent scientist.

All those do not necessarily make his ENCODE-related paper correct, but we will hold the judgement until we manage to read it carefully. Here is the full abstract –

A recent slew of ENCODE Consortium publications, specifically the article signed by all Consortium members, put forward the idea that more than 80% of the human genome is functional. This claim flies in the face of current estimates according to which the fraction of the genome that is evolutionarily conserved through purifying selection is under 10%. Thus, according to the ENCODE Consortium, a biological function can be maintained indefinitely without selection, which implies that at least 80 – 10 = 70% of the genome is perfectly invulnerable to deleterious mutations, either because no mutation can ever occur in these “functional” regions, or because no mutation in these regions can ever be deleterious. This absurd conclusion was reached through various means, chiefly (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. Here, we detail the many logical and methodological transgressions involved in assigning functionality to almost every nucleotide in the human genome. The ENCODE results were predicted by one of its authors to necessitate the rewriting of textbooks. We agree, many textbooks dealing with marketing, mass-media hype, and public relations may well have to be rewritten.




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5 comments to Was ENCODE’s Claim of 80% of Human Genome Being Functional all Hype?

  • Joe

    Why not contact the corresponding author?

  • admin

    Joe, Are you asking us to contact the corresponding author of Genome Biology paper, or ENCODE paper?

  • […] Was ENCODE’s Claim of 80% of Human Genome Being Functional all Hype? […]

  • Mikael

    I think there is some merit in Graur et al’s criticism, but they are also guilty of some misinterpretation. For example this passage from the paper:

    “They also found that more than 80% of the transcription start sites were contained within open chromatin regions. In yet another breathtaking example of affirming the consequent, ENCODE makes the reverse
    claim, and adds all open chromatin regions to the “functional” pile, turning the mostly
    true statement “most transcription start sites are found within open chromatin regions”
    into the entirely false statement “most open chromatin regions are functional transcription
    start sites.”

    I don’t see anything in the ENCODE papers that suggests that the authors believe that “most open chromatin regions are functional transcription start sites.” I was a co-author on the Song 2011 paper on open chromatin and we certainly didn’t claim that. As for myself I have been more interested in interpreting some of the open chromatin regions as putative enhancers.

  • admin

    Mikael, we requested Dar Graur to comment on your point, and hopefully hear from him soon.

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