Author: Mike White

Genomes, Books, and Science Fiction

ENCODE Media FAIL (or, Where’s the Null Hypothesis?)

I’m ready to drink myself into a stupor, and not because it’s my birthday. This week we’re seeing a massive science reporting fail on a large scale. And just to be clear, I’m not only (or even mostly) blaming reporters.

We’ve known for a long time that protein-coding genes are regulated by non-coding DNA sequences, ‘gene switches’, if you will. We’ve known for decades that the genome contains many ‘gene switches’. (See the references in this review.) That’s uncontested.

ENCODE is significant because they’ve provided a very useful data set, and not because they’ve a) shown that non-coding DNA is important (we knew that), or b) most of the genome has phenotypically important regulatory function (it does not), or c) that most of the genome is evolutionarily conserved (not true either). What they have shown is that much of the genome is covered by introns, and it is hard to find biochemically inert DNA, which those of us who’ve tried to generate random, ‘neutral’ DNA sequences (for say, spacers in synthetic promoter experiments) will agree with.

Now, let’s see how major media stories are handling the significance of ENCODE (h/t to Ryan Gregory for compiling the list of stories): Continue reading “ENCODE Media FAIL (or, Where’s the Null Hypothesis?)”

ENCODE Decodes the genome… but how much is functional?

The latest round of ENCODE papers are out, accessible via a handy ENCODE explorer gateway at Nature. I know what I’ll be doing for the next week. Stay tuned for more Finch & Pea coverage of what all this means, but I can’t resist a few brief comments about function.

First, you can immediately dismiss the NY Times’s misleading headline that suggests much, much more of the genome is functional than we previously thought. Being an intron counts as ‘function’ here, which is a pretty low bar to meet. The ENCODE results indicate that much of the genome is represented within introns, which I find fascinating, but that’s not something that forces us to dramatically revise our ideas about function in the genome.

Second, I’m going to claim (without any proof whatsoever) the title of the world’s record holder for “the largest number of randomly generated DNA sequences tested for function in an enhancer assay.” Hopefully in the not too distant future you can read in print about the 1000+ random sequences (plus several thousand genomic sequences) we tested in our new, smokin’ hot, high-throughput enhancer assay, but here’s the punch line: it’s not that difficult to randomly generate a DNA sequence that will drive substantial tissue-specific transcription.

In other words, whether it’s been selected for function or not, DNA is generally not biochemically inert.

P.S. This seems to be consistent with Ewan Birney’s comment, “It’s clear that 80% of the genome has a specific biochemical activity – whatever that might be.”

P.P.S. Brief methods: We took sequences under ChIP-seq peaks, thoroughly scrambled them while preserving the original di-nucleotide frequencies, and dropped them upstream of a basal promoter to test for enhancer activity.

If you want a paradigm shift, don’t go looking for it

“In science… novelty emerges only with difficulty, manifested by resistance, against a background provided by expectation.” – Thomas Kuhn, The Structure of Scientific Revolutions

Organizations that fund scientific research love to call for paradigm-shifting proposals. And scientists love to think that their latest work is smashing down staid, old paradigms. But this focus on paradigm shifting gets Thomas Kuhn exactly backwards. If you want a paradigm shift, don’t go looking for it.

That’s Kuhn’s major point in this week’s The Structure of Scientific Revolutions reading. Last week, we had a broad discussion of Kuhn’s ideas about pre-paradigm science, what a paradigm is, and why normal science is like solving puzzles. This week we’re going to be a little more focused: we’re going to talk about four pages – p. 62-65 – instead of four chapters.

Read these four pages, and you’ll understand more about Kuhn’s view of science than just about anyone who talks about paradigm-shifting. Continue reading “If you want a paradigm shift, don’t go looking for it”

Sunday Science Poem: Melville and Mechanized War

When you think about poetry and the Civil War, Herman Melville is probably not the first person who comes to mind. Yet, with some serious hindsight, Melville has turned out to be one of the major poets of the Civil War. As readers of Moby Dick, White-Jacket, and “the Bell Tower” know, Melville had a longstanding interest in technology, science, and the mechanization of society. This made Melville especially attuned the effects of technology on war, and on the role of soldiers in war.

This week’s Sunday Science Poem is “A Utilitarian View of the Monitor’s Fight.” The Monitor was the first Federal armored “ironclad” warship. On March 8, 1862, the Monitor and the Confederate Virginia (previously known as the Merrimac when it was a Federal ship) battled to a draw in the world’s first battle between armored warships – an ominous milestone that Melville explores in this poem. This was a battle of “no passion; all went by on crank, pivot, and screw, and calculations of caloric.” It was not a glorious fight of heroes, but a professional battle of technical “operatives.” Today, the operatives can control unmanned, mechanical weapons without even being present on the battlefield. Continue reading “Sunday Science Poem: Melville and Mechanized War”

How science climbs out of the chaotic morass and into paradigms and puzzles

Welcome to the first meeting of The Finch and Pea’s The Structure of Scientific Revolutions 50th anniversary bull session book club. Grab a drink, pull up a chair, and let’s talk about the first four chapters of that book you always meant to read.

First, a brief word about the preface. Certain famous books are prefaced with apologetic comments by the author, warning us that what is to follow is just an outline or a sketch. We tend to smirk of over the fact that Darwin considered his 502-page behemoth just an abstract. Kuhn says similar things in his preface to Structure, but in this case I take Kuhn’s apologies more seriously. Historical examples are important in this book, but Kuhn tends to allude to episodes in the history of science, rather than discuss them – at least in the first four chapters. Perhaps this is fitting, because in Kuhn’s view, a successful paradigm necessarily leaves a lot left to be done. Continue reading “How science climbs out of the chaotic morass and into paradigms and puzzles”