人類基因組詳圖/DNA元件百科全書/ENCODE 被吐槽的主要原因是什麼，它們有道理嗎？

01-12

ENCODE項目被噴的比較多，原因主要有兩點：

1. 寫文章不太嚴謹，毫無根據的論斷張口就來，比如著名的「80%的人類基因組有功能的」。這點已被無數搞進化的吐槽。比如Let』s Discuss這裡摘了一段：

On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE
A recent slew of ENCyclopedia Of DNA Elements (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 less than 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 by employing the seldom used 「causal role」 definition of biological function and then applying it inconsistently to different biochemical properties, by committing a logical fallacy known as 「affirming the consequent,」 by failing to appreciate the crucial difference between 「junk DNA」 and 「garbage DNA,」 by using analytical methods that yield biased errors and inflate estimates of functionality, by favoring statistical sensitivity over specificity, and 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.
該吐槽文發表於 Genome Biol Evol. 2013;5(3):578-90. doi: 10.1093/gbe/evt028

2. 進一步導致科研經費分配不均(更多千老在哭泣。。。)

聽老闆說，當初搞人類基因組計劃的目的是徹底搞定癌症。

現在我們知道，基因組後面還有修飾、轉錄、可變剪切、轉錄後編輯、翻譯後蛋白修飾、通道互做等等等等一堆東西，所以離攻克癌症這個宏偉目標還很遠……

而人類基因組計劃砸了很多很多錢……

被吐槽啥了？這沒頭沒尾的，你想問啥

我自己的吐槽，人類基因組計劃和後來的DNA元件百科全書大概相當於：

老闆看好一款國外軟體，苦於不知道怎麼復(山)制(寨)

碼農跑過來說：老闆，我水平夠了，你給我30億刀，我給你搞定啊？

雖然貴的肉疼，但老闆想到軟體能帶來的種種好處，咬牙給了碼農30億刀，號召全公司一起干

大家熱火朝天的幹了13年，終於有結果了

老闆：快快，把結果弄來我看看

碼農：好嘞，1110010101000100111010011000100111001110111010110……(30億個哦)

老闆：………………………… (╯°Д°)╯︵ ┴─┴

只是知道了ATGC的排布如同只是知道了脈衝電信號罷了，別說軟體化了，離反推出源代碼還遠著吶，吐槽的可能是把該計劃的作用片面誇大了吧。

但是，人類基因組計劃就像吃下去的第一個肉包子，別來問我吃四個肉包子就飽了幹嘛不直接吃第四個，還能省仨。

外教把關於ENCODE相互撕逼的論文貼出來講了一節課…

爭議主要在於ENCODE宣稱有80%的基因都是functional這裡吧。

大概是ENCODE關於基因「functional」的定位太寬泛了。 ENCODE項目關於functional的定位實際上是基於"biochemical
evidence"的，但學術上對於FUNCTIONAL的定義實際上更廣泛是採用「evolutionary evidence」and「genetic
evidence」，三者的關係大概是這個

可以看出來，Biochemical evidence 包含的基因比上述兩種標準包含的基因本身就要多。

有科學家吐槽說，Encode說80%的基因都是functional的實際是指80%的基因都是「are very likely to have causal roles in phenomena deemed relevant to biomedical research.「，換句話說，就是看上去有功能，但是實際上都是沒有卵用的功能。最經典的反駁論據就是，洋蔥的genome長度是人類的5倍，按照ENCODE的標準，洋蔥的結構應該是比人類複雜的多才對，而實際上著多出來的五倍有可能是在evolution過程中冗餘的基因，但它們對洋蔥也沒有什麼壞處，也就慢慢保留下來了。

貼兩篇外教特意挑出來講的關於ENCODE的論文裝裝逼