Deputy Director General of EMBL, Director of EMBL-EBI. I have an insatiable love of biology. @ewanbirney@genomic.social. I also work with ONT, Dovetail + GeL.
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Oct 13 • 46 tweets • 8 min read
So @JeremyFarrar asked for an "explainer thread" on Noble Prizes in Chemistry around AlphaFold and Protein design, so here goes.
First off, this is an old problem. It starts with observations in the 1950s/1960s, leading to a Noble Prize in 1972 to Anfinsen, Moore and Stein where in particular Anfinsen convincingly shows that the particular sequence of amino acids in a protein determines its 3D structure
Sep 3 • 24 tweets • 5 min read
Great to see this paper out by @D_Westergaard and colleagues - including myself - leveraging the just jaw-droppingly good combination of the Danish pedigree data (across the entire country!) and their highly detailed EHR. nature.com/articles/s4146…
This is pedigree based genetics - the correlation of phenotypes (in this case diagnoses of diseases) - as was done in the 1910s - formalised by RA Fischer and S. Wright from ideas at the turn of the 20th Cent.
Sep 1 • 27 tweets • 5 min read
One of the more depressing things re-engaging on social media is the undercurrent of pseudo-scientific racism which continues to pop up with exciting data rich plots, often lots of maths and just lots of class A bullshit justifying tired anti-woke (but just ol' fashioned racist)
I'm not going to amplify the crappy threads/blogs/messages forwarded to me, but I do want to arm my followers with the most cogent arguments against this if this does come up in conversation around you.
Jul 24 • 8 tweets • 1 min read
A reminder ( it’s an evergreen topic) - humans are a genetically undiverse species - we exploded out Africa in a heartbeat of evolutionary time and we predominantly adapted to the multitude of environments by our behaviour, passing that knowledge down culturally in groups
Although there are genetic adaptations to some environments- eg lack of sunlight (fair skin), regular milk consumption (lactase persistence) or reduced sweat for humid environments (less sweat pores and thicker hair) these have two features
Apr 2 • 20 tweets • 3 min read
A short, personal thread on what is odd about other cultures when interacting with Brits, and then also what I think is odd about Brits when interacting with other cultures - highly, highly personal, but from >30 years working internationally.
German+Dutch do not have to preface a challenge with "I think you might have missed something..." or some other British-style softening up. It is entirely fine - indeed polite/shows respect - just come out "you are wrong because X,Y" - this directness is surprising for a Brit.
Feb 20 • 28 tweets • 5 min read
The publication of the whole genomes from the US @AllofUsResearch cohort is great to see, but the choice of how to represent an overview of the genetic relationships has (rightly) drawn controversy, in particular how the concepts of ethnicity and race are mapped to it.
This is not in bad faith - the AllofUs cohort should be applauded in its diversity push and much of the but it is an illustration of the messiness of genetics and the inability to represent our complex relationships in any 2D space. Longer thread below>>
Jan 19 • 18 tweets • 3 min read
Next monday is 4 hours of preliminary grant reviews - a necessary but intense part of being a scientist who goes through peer review is being the reviewer. As ever, I am rather amazed by scientists who make simple mistakes in their proposals. My thoughts for a good proposal:
For me as a reviewer you need to convince me of 4 major things. >>
Dec 10, 2023 • 25 tweets • 4 min read
It is a dark, drizzly december sunday in London and I've just read yet another depressing thread of someone reaching for genetics to justify racism and superiority to themselves. It is deeply wrong, but such a recurrent thread worth both dismantling+ understanding the attraction
Let's dismantle first; although a feature of ethnicity/race is skin colour and other visible features, and although these have strong genetic components, counter-intutively for most people, ethnicity is *not* a good predictor for genetics
May 21, 2023 • 34 tweets • 7 min read
Here is the slightly cheesy montage for the great #nanoporeconf for 2023 - and, with a reminder of my conflict of interest - I am a longestablished paid consultant for Oxford Nanopore and a shareholder - here are my thoughts on the conference.
For long time nanopore scientists -and I am definitely one of those- one can definitely both plot progress London Calling conference (on the Thames in London) both in terms of what the company presents as near and long horizon+how the plenary speakers use and talk about nanopore
May 21, 2023 • 6 tweets • 2 min read
My friend and economics/ markets guru @felixmwmartin commenting on super human AI and all too human market behaviour - on the money that AI will transform many things (science included - it has started in earnest) but also more broadly in the economy
Economics and biology are closer in data science than you might think - in particular micro economics and observational human biology aka epidemiology. Plenty of differences but lots of overlap as well, eg biased sampling, many hidden confounders, clearly correlated variables
May 11, 2023 • 16 tweets • 5 min read
The @HumanPangenome - the 3rd chapter. For an intro into the human pangenome, check out this thread -
but now on to the weirdest "our genome does that!" moment. Brace yourself for genome geekery
We, like most other organisms, have a particular thing when we make sperm or eggs (depending on our sex) - we have an enforced "shuffle the deck" our parent's genome - this is called crossing over or recombination in meiosis.
May 10, 2023 • 15 tweets • 5 min read
It was a tour de force just generating a draft human pan-genome @HumanPangenome, but some suspected and some utterly bizarre things about the human genome have been revealed using these 47 different human reference quality genomes.
For a primer on human pan-genomes, here is a thread that will take you through this. Read this first before going into the weird and wonderful world of our genome.
Congratulations to the @HumanPangenome - in particular @BenedictPaten for his leadership + highlighting @ensembl's role via Fergal Martin in annotation. For the rest of this thread I will explain this technical genomics tour de force using... Shakespeare nature.com/articles/s4158…
Shakespeare wrote a considerable number of pieces of work; English was a very fluid language and so his own spelling was quite variable and then subsequent copying errors and improvements have led to many differences in the documents representing this work.
Apr 16, 2023 • 10 tweets • 2 min read
This is part right (“we’re on a cusp of further genetic understanding of health etc) and then straightforwardly *wrong* on its implication (“there are inherent differences between groups”) and this pseudoscience twoodle by @GoodwinMJ needs … debunking >>
Basically humans don’t come groups - we exploded across and out of Africa very quickly (in evolutionary time) and we’ve moved and mixed ever since - in antiquity as well as now
Apr 15, 2023 • 23 tweets • 5 min read
A saturday morning muse triggered by a great random meeting of the Norwegian cohort community in Bristol, due as ever to the pro-social @mendel_random and @carolinerelton, on the convergence of population health genetics to clinical genomics.
Some history - keeping track and analysing cohorts of humans has a long pedigree in science, and is one of the fundamental tools in epidemiology. There are two things one has to addree (a) logistics in recruiting and tracking dominate cost and effectiveness (b) ascertainment
Mar 27, 2023 • 23 tweets • 3 min read
A brief muse on a longstanding theme of mine - that ethnicity assignment is a very different process than genetics, with the only commonality being that one of the salient features for ethnicity assignment - skin colour - has strong (and very complex) genetics.
It's worth reminding people that there is not a set of universal ethnicity categories; the categories provided in forms are inherently cultural. The US census has one set; UK recording another; Germany one more; India v. different + in France it is illegal to ask about ethnicity
Feb 22, 2023 • 10 tweets • 2 min read
Having some more sympathy for people coming into genomics/genetics from other fields on design - the rule-of-thumb of about 1,000 cases (I'll come onto why I like more like 5,000+ later) is partly about effect size but mainly about allele frequency - and their combination
So, from other fields, you'd be familiar with effect size from power calculations - what is the minimum sample size to be 80% confident you would pick up a result with an effect size of X (usually expressed in some normalised manner).
Feb 22, 2023 • 14 tweets • 2 min read
Grrr. It's 2023, and can we please stop funding/commissioning/publishing human genetic association studies with cases <1,000 (on case/control) or <1,000 overall (quantitative traits) in humans. It is just not going to work well. We know this.
Additional moan; if you do Whole Exome/Genome sequencing you need *more* power to just be able to ask the question about rare variants (the word rare here is a hint). The fact that you generated a more accurate genome doesn't magically create power in your statistical analysis.
Feb 19, 2023 • 29 tweets • 6 min read
Thoughts after a week's break on using polygenic scores in medicine: TL;DR Polygenic scores are robust and useful; their utility and deployment in medicine is mainly a function of utility and risk of interventions downstream; embryo selection by PGS is riskier than other uses
Context: I am an expert in (human and other) genomics and genetics, but not a clinical researcher - however I do work with a variety of clinicians. I understand and use polygenic scores in my research. I am not a IVF/Embryologist, but do know researchers in this area.
Feb 18, 2023 • 4 tweets • 2 min read
Got a PhD in genomics/genetics or data science? Want a postdoc in exploring cutting edge techniques in genetics? Interested in coming to Cambridge UK area, working with a team looking at genetics from human to medaka fish - this job could be for you! embl.org/jobs/position/…
This is a postdoc in my research group @emblebi and we have a dynamic group looking at genetics and genomics in particular in Medaka fish and Humans. The postdoc here will be analysing (already generated) RNAseq data and ONT derived long reads and methylation in the MIKK panel
Feb 8, 2023 • 28 tweets • 5 min read
Genome editing has made the news this week in some contexts, and I wanted to provide a primer to this. TL;DR our ability to change ("edit") DNA radically changed ~2010 ish and its impact will continue grow.
The technology is called CRISPR (or, in full, CRISPR/Cas9). Its discovery rightfully was the reason why Emmanuel Charpentier and Jennifer Doudna was awarded in the Nobel Prize in 2020 (nobelprize.org/prizes/chemist…)
