Getting to watch Dan Turner on LamPORE for #nanoporeconf explain how LamPORE works. Reminds us about how LAMP works - isothermal (just heat, dont heat cycle) and make insane amounts of DNA (micrograms) ("explosive amplification")
LAMP traditionally coupled to a colour change (of flourescent primers nearby) but these have false positives (weird dimers) and dodgy "mid colour" changes. Rather than using fluorophore, ligate nanopore primers, and then put on a nanopore
LAMP gives multiple copies of the target into a long read, and it can have a 10nt bar code. Easy dual bar code, but also the first "LAMP" barcode is *in the LAMP tube*. By having a beta-actin internal control to distinguish "negatives" from "failed reaction" / "failed swab"
Very impressive ROC curve from Dan - as close to a right angle triangle as you might like. On real samples - Ct 19 (easy) to 36 (hard). Assay being validated by external collaborators.
Future: Aiming for folding in adaptive sampling for key regions for host response (!) (this is using the magic from @mattloose)
Aiming to remove sample extraction bottleneck - move from swabs to saliva - inactivate viruses first and then LAMP works (brill!) and have a respiratory panel - a multiplex primers across many primers. Synthetic coinfected mixture works.
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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
Just to visualise this; think of amino acid chain as different sorts of beads on a string. The beads come in 20 types - some type like to stick to other types; some types like to be hidden away from water; some are small and some are large. A protein is somewhere around 50 beads
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.
This concept of the correlation of phenotype to pedigree predates the identification of DNA as molecular mechanism for inheritance - this is old school genetics updated in the modern age.
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.
First off, humans are a super-young species - we exploded out of Africa very quickly and although lots of the details we still don't know (and the science changes quickly) it's pretty clear we adapted to the changing environment main by behaviour
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
Firstly these adaptions are sparse in the context of the genome - its small regions which do this
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.
Northern (Protestant/river/Prussian) Germans are very different from Southern (Catholic, Mountain+Forest) Germans. Don't confuse them. External stereotypes of Germans (in particular in Britain) is a weird mixture of both and you have to untangle this.
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>>
A reminder that genetics (the variation in DNA sequence passed down from your parents, +their parents etc) and race or ethnicity (a box people tick on surveys or on census) are quite different concepts, strongly linked only by visible features which are genetic, eg, skin colour