When I’ve planned and set up an experiment for weeks and fails on the last day because the light went out

falling

Leave a comment

Asking in the lab who last used a reagent which has ran out

AsXxi9F

Leave a comment

When a competitor asks me what genes I’m studying next

tumblr_inline_mil42jEdrN1qz4rgp

Leave a comment

When someone uses Comic Sans in a presentation

wtf f0jL6

1 Comment

Publishing like a Boss

Well, that’s a very productive May 2nd, 1997.

205352_10150948987783779_410557237_n

Well played, Jay, well played.

Leave a comment

How I feel when I see freshmen in the University cafeteria and realize I still have several months left here

tumblr_mea6p6kNWw1qjom7ao3_r3_500

Soon… I will graduate soon…. hopefully.

Leave a comment

Reflections of a “Small Journal” Editor

Yet, without a thick skin, the patience of Job, and an enduring sense of humor, the hard-hit small editor would probably not last through a single cycle of his journal, laboring as he must under the curses of author uncomprehension, author uncooperativeness, author irresponsibility,and sometimes even downright stupidity

John O. Corliss

Leave a comment

Watson at the Eagle pub, 60 years later.

The Eagle is a pub at Cambridge, originally opened in 1667, which Jim Watson and the great Francis Crick, among others, used to visit during their time at the Cavendish Laboratory.

If you’ve read the Double Helix, you’ll be very familiar with it. If you haven’t, stop reading this post and go get a copy at Amazon. You won’t regret it.

Anyway, a great pic was posted in Twitter a few days ago, and I wanted to share it with you.

It was on February 28th, 1953, that Watson and Crick claimed they had cracked a big problem they have been working on; in fact Crick is said to have stormed into the Eagle proclaiming that they had ” found the secret of life”: they finally had a model for the structure of DNA.

Later that year, in April, the idea was formalized in the classic Nature paper.

2013 then, marks the 60th anniversary of this event, which opened the path for the explosion of molecular biology as a field.

Watson, now 84, appears in this great pic, taken to commemorate such an important event in the history of biological research. He is, of course, having a beer, like great scientists do.

Although this is not the original Eagle pub in Cambridge, but the one at CSHL, it is still a nice photograph.

BEOIrKcCQAAw23S.jpg large.jpg%20large
(Picture credit: CSHLnews)

Just for comparison, this is a picture taken of both of them in 1959.

james-watson-and-francis-crick-in-1959

(Image credit)

2 Comments

When I read an article and notice I’ve been scooped….

crying 14loqba

Leave a comment

The ENCODE “takedown” paper: some quotes

Soon after the recent set of ENCODE papers came out, several scientists raised concerns regarding the estimates about the encodefraction of the genome that appears to be functional, that the authors put forward: according to them, ~80% of the human genome is functional.
This, of course, greatly differs to what most of us think, considering, among other things, that the fraction of the genome that is evolutionarily conserved through purifying selection appears to be under 10% (what about the rest? We think it divides between junk DNA and some “unknowns”).

The problem mainly arose from the definition of “functional” that ENCODE used, one that is so loose, that may not be useful at all.

In fact, “according to ENCODE, for a DNA segment to be ascribed functionality it needs to (1) be transcribed or (2) associated with a modified histone or (3) located in an open-chromatin area or (4) to bind a transcription factors or (5) to contain a methylated CpG dinucleotide” (Graur et al., 2013). You would agree that this criteria is very lenient, hence, the 80% estimate.

A recent paper, ruthlessly discusses the ENCODE paper and takes great issue with the “80%” estimate. The authors “detail the many logical and methodological transgressions involved in assigning functionality to almost every nucleotide in the human genome“. The manuscript reviewers could have suggested the authors to tone it down a little, but from what I found out in the web, evolutionary biologists tend to be very strong about their opinions on paper, when discussing the work of others they disagree with.

I encourage you to read the article, which is freely available. In the meantime, here are a few quotes:

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.

ENCODE adopted a strong version of the causal role definition of function, according to which a functional element is a discrete genome segment that produces a protein or an RNA or displays a reproducible biochemical signature (for example, protein binding). Oddly, ENCODE not only uses the wrong concept of functionality, it uses it wrongly and inconsistently

We identified three main statistical infractions. ENCODE used methodologies encouraging biased errors in favor of inflating estimates of functionality, it consistently and excessively favored sensitivity over specificity, and it paid unwarranted attention to statistical significance, rather than to the magnitude of the effect.

At this point, we must ask ourselves, what is the aim of ENCODE: Is it to identify every possible functional element at the expense of increasing the number of elements that are falsely identified as functional? Or is it to create a list of functional elements that is as free of false positives as possible

Comparative studies have repeatedly shown that pseudogenes, which have been so defined because they lack coding potential due to the presence of disruptive mutations, evolve very rapidly and are mostly subject to no functional constraint (Pei et al. 2012). Hence, regardless of their transcriptional or translational status, pseudogenes are nonfunctional!

For example, according to ENCODE, the putative function of the H4K20me1 modification is “preference for 5’ end of genes.” This is akin to asserting that the function of the White House is to occupy the lot of land at the 1600 block of Pennsylvania Avenue in Washington, D.C.

So, what have we learned from the efforts of 442 researchers consuming 288 million dollars? According to Eric Lander, a Human Genome Project luminary, ENCODE is the “Google Maps of the human genome” (Durbin et al. 2010). We beg to differ, ENCODE is considerably worse than even Apple Maps.

Evolutionary conservation may be frustratingly silent on the nature of the functions it highlights, but progress in understanding the functional significance of DNA sequences can only be achieved by not
ignoring evolutionary principles

High-throughput genomics and the centralization of science funding have enabled Big Science to generate “high-impact false positives” by the truckload (The PLoS Medicine Editors 2005; Platt et al. 2010; Anonymous 2012; MacArthur 2012; Moyer 2012). Those involved in Big Science will do well to remember the depressingly true popular maxim: “If it is too good to be true, it is too good to be true.”

We conclude that the ENCODE Consortium has, so far, failed to provide a compelling reason to abandon the prevailing understanding among evolutionary biologists according to which most of the human genome is devoid of function

(…) 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 (…)

Leave a comment