Seth Howes

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Seth Howes

Seth Howes

@SethSHowes

🩺 doctor defected to tech 👨🏼‍💻 prev engineer @exolabs | medicine @uniofoxford | ML @imperialcollege

London, England Katılım Ağustos 2021
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Seth Howes
Seth Howes@SethSHowes·
I’ve wanted to do this for a decade. But I never did - I refuse to give any company my DNA. It is me. So this week I sequenced my genome entirely at home. Literally on my kitchen table. I never exposed my DNA sequence to the internet. Not at any point. I used a MinION to do the sequencing (it’s smaller + weighs less than an iPhone). I used open-source DNA models for the analysis (Evo2 and AlphaGenome) running locally on a DGX Spark and Mac Studio. I traced mechanisms behind my family’s multigenerational autoimmune conditions that no clinician has been able to understand. When I set out to do this I didn’t know if it would actually work. It does. Your genome is the most private data you will ever have. You probably shouldn’t let it leave your house.
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Patrick Collison@patrickc

I'm lucky enough to have a great doctor and access to excellent Bay Area medical care. I've taken lots of standard screening tests over the years and have tried lots of "health tech" devices and tools. With all this said, by far the most useful preventative medical advice that I've ever received has come from unleashing coding agents on my genome, having them investigate my specific mutations, and having them recommend specific follow-on tests and treatments. Population averages are population averages, but we ourselves are not averages. For example, it turns out that I probably have a 30x(!) higher-than-average predisposition to melanoma. Fortunately, there are both specific supplements that help counteract the particular mutations I have, and of course I can significantly dial up my screening frequency. So, this is very useful to know. I don't know exactly how much the analysis cost, but probably less than $100. Sequencing my genome cost a few hundred dollars. (One often sees papers and articles claiming that models aren't very good at medical reasoning. These analyses are usually based on employing several-year-old models, which is a kind of ludicrous malpractice. It is true that you still have to carefully monitor the agents' reasoning, and they do on occasion jump to conclusions or skip steps, requiring some nudging and re-steering. But, overall, they are almost literally infinitely better for this kind of work than what one can otherwise obtain today.) There are still lots of questions about how this will diffuse and get adopted, but it seems very clear that medical practice is about to improve enormously. Exciting times!

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Seth Howes
Seth Howes@SethSHowes·
@MathSRIsh I want to reduce time taken. 4-5 MinION flow cells will take 2 weeks + sample and library preps and flow cell prep for each
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Mathurin Dorel
Mathurin Dorel@MathSRIsh·
@SethSHowes Why don't you just run 4-5 MinION flowcells ? Slightly more expensive but the result is the same and you already have the hardware.
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Seth Howes
Seth Howes@SethSHowes·
I want to loan / buy a PromethION 2 Solo, so I can do 30x WGS at home. I want to record myself running the full sequencing protocol end-to-end, and post the video. If you are open to this, or know of somehow who may be, please DM me.
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Clinton M
Clinton M@CooKeMonter·
@SethSHowes I'm pretty sure Danny Chen and Digby Usher ran a lab at Imperial College or at least they did in 2024, I think they moved here. lifefabs.bio/about
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Seth Howes
Seth Howes@SethSHowes·
Recent interest in DIY bio has led me to ponder this question: Will we ever see a hacker movement in biology akin to what we saw with personal computing in the 1970s? Take homebrew computer club as a reference. You had a bunch of amateur electronic enthusiasts congregate to mess around within a given technology domain. To see what they could build, and share their ideas. Then you have a cambrian explosion of technological development in personal computing, because the component technologies are now accessible to individuals outside of the institutions that facilitated their early development. What is structurally similar / different about the spaces of computing in 1975 and biology in 2026? Are the differences sufficiently great that the 'homebrew biology club' never exists?
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Seth Howes
Seth Howes@SethSHowes·
@j0hnparkhill Observability when hacking biological systems is so limited. It’s 1) hard to get -> ridiculously sparse 2) hard to interpret 3) low-dimensional relative to what you need to effectively understand and therefore debug the system
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johnparkhill
johnparkhill@j0hnparkhill·
@SethSHowes Just a matter of time IMO. The biggest blocker right now is the lack of a "apple 1 display circuit". Characterizing the biology you are engineering would often be cost-prohibitive without clever experimental design...
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Seth Howes
Seth Howes@SethSHowes·
@MolBioMike @jithinbp_ How did you get the price this low? What PSU did you use? This component I can’t find for less than $100
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MolBioMike
MolBioMike@MolBioMike·
@jithinbp_ @SethSHowes I’ve built an electrophoresis rig for ~50$ I’ll put it out there when I have DNA and some reagents to test
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Seth Howes
Seth Howes@SethSHowes·
A Qubit costs ~$5,260. I built one for $39. Not a toy version. A fully working DNA fluorometer: the device you use to measure how much DNA there is in a sample. This mattered because my first sequencing run underperformed partly because I didn’t know exactly how much DNA I was loading. For nanopore sequencing, input DNA quality matters a lot. Too little and the pores are underutilised. Too much and flow cell longevity is compromised. The underlying device is not complicated. A DNA fluorometer works by adding a dye that binds to DNA, shining light at the sample, and measuring the fluorescence. The BOM is basically: > $23 optics + sensor > $8 Arduino/electronics > $6 screws/nuts > $2 enclosure plastic Biotech especially is full of equipment with insane idiot indexes. With AI you don't really have an excuse not to 1) work out what that the index for a piece of equipment is and 2) build your own version if it's irrationally high. THINK BEFORE YOU BUY.
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Seth Howes
Seth Howes@SethSHowes·
@kirk3gaard @impossible_eng This is useful to know. The ONT guidance is akin to “don’t use too much it will affect yield”, but I’m much more inclined to believe this
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montag
montag@impossible_eng·
@SethSHowes How did you verify your accuracy?
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Seth Howes
Seth Howes@SethSHowes·
@adic_9 Only being able to order reagents in bulk is a massive issue. Minimum order for Qubit dsDNA reagent is 100 samples at ~$110 per box. And this is cheap relatively speaking. Someone should setup a company that bulk buys reagents and allows you to buy just what you need.
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adic
adic@adic_9·
@SethSHowes Cool! Usually they’re pretty expensive up front bc quantities but that’s nice
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Seth Howes
Seth Howes@SethSHowes·
@adic_9 <$0.13 if you use SYBR Safe dye. I used a slightly more expensive dye today at ~$1.10 per run
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Bryan Johnson
Bryan Johnson@bryan_johnson·
weekend plans
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Crémieux
Crémieux@cremieuxrecueil·
Horses call for immediate suspension of automotive vehicle experiment
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Seth Howes
Seth Howes@SethSHowes·
@The__Taybor I’m so sad this device was cancelled - I almost used the PromethION 2 SOLO instead of the MinION for my run so I could get 30x coverage across the entire genome. Didn’t manage to source one unfortunately. I just hope the MinION doesn’t go the same way…
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Seth Howes
Seth Howes@SethSHowes·
@Fresno_Famous DNA fluorometer - tells you how much DNA you have so you load the right amount to the sequencer
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Seth Howes
Seth Howes@SethSHowes·
today electronics. tomorrow wet lab bio. you can just do stuff.
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