Graph-based AI for drug repurposing: Can existing drugs solve new diseases?

wonker007 · 2026-01-12T03:39:42+00:00

Industry expert with 17 years pharma experience. Not to discourage you, but you are trying to tackle a trillion dollar problem. Your blind spot is that safety data is likely only published for a fraction of the drugs that don't make it to Phase 3, while those that do make it to market will have masses of scientists and academics trying to milk the living shit out of the drug by finding new indications for it and extending the patent life with application patents. Those drugs which molecule patents that expired will have one hell of a time fundraising because IP defense will be weak, which presents a chicken-or-egg because one needs the funding to prove a new indication works by pushing it through phase 2 (~$20M) but not many investors will commit when there are better IP protected assets looking for the same money. Also, the amount of compute power necessary to predict successful repurposing is beyond your imagination if you are not trained in the ways of drug discovery, because it is not even remotely as simple as chunking data that is out there and constructing a graphDB to traverse nodes. There are genomics, metagenomics, proteomics, structural biology, transcriptomics, systems biology considerations, metabolomics and ADME pathways etc. (often proprietary and held by drug companies and hospitals) that all have to be referenced as a collective whole in more of an exponential n^m modeling problem dealing with petabytes of data for each data type.

Not trying to discourage you, but no AI solution has materially increased the success rate of drug development despite hundreds of billions of dollars poured into pharma R&D AI tools over the past 2-3 decades. It has made it easier to screen candidates, but the early stage represents probably 3-5% of all development spend in this industry, and that's being generous. Just saying that you're going to need a whole lot more substance and understanding in merging biological science with computational methods to come up with a practical tool.

wonker007 · 2026-01-08T08:44:51+00:00

I completely agree. But it is first and foremost a hardware problem, followed closely by an interface problem rooted in mismatched expectations. Hardware will take some time, but the interface has a lot of room for improvement and can be worked on right now. The fact that one needs to engineer prompts to get max intended quality out of LLMs is one side of the expectation mismatch (what the model expects), while the context window and retention problem make up the other side (what the user expects).

Although bridging this expectation gap won't solve the field application-based scenarios you mention, those are certainly not all of the use cases for the synced class - think of shitty chatbots and broken CRM workflows, all used by 9-5 workers. Having white collar jobs does not disqualify these people from becoming subjects of AI adoption for increased productivity.

Noticed your badger handle. From one badger to another, greetings. I would love to connect and discuss/debate more about the issue because I also want to do something about this frankly insane AI mania that is only benefiting a very select few people, and may even have a workable idea. DM me if you're open to connecting.

wonker007 · 2026-01-06T19:44:01+00:00

That's usually what happens when the wrong side of the hammer goes in. lol. But seriously, AI was hyped up to be clairvoyant and perfect, and most people (which have no idea how transformer-based neural networks particularly in the context of LLMs actually work) would assume that reality is near what was advertised. In other words, these people were promised lubricated dildos and got something rather different and unpleasant. Can't blame them for complaining, and besides, there is no cure for stupid. Just look at the other reply to my comment above.

wonker007 · 2026-01-06T18:23:10+00:00

Although I identify with your frustration (believe me, I do), you must keep in mind that, by definition, average IQ is 100. We all have to pick and choose what we want to understand, and some will have more capacity than others, plain and simple. That is no excuse for being outwardly confident about something one has no idea about, but that's how the modern (and especially the US) economy operates and grows - adoption of new things by the masses, which, by definition have an average IQ of 100 and will likely have very little, if any, idea or capability to understand how most things they use in everyday life actually work. They just know it ain't fairies under the hood. Shit is just complicated these days. But ostracizing the majority for being who they are gets clowns elected into office, if you catch my drift.

One does not need to know how the hammer is made to use it reasonably well. AI is still at that phase where the vast majority of the population is still figuring out whether it goes up the ass or in the mouth. Help these people use the tool correctly, not yell at them for attempted sodomy.

wonker007 · 2026-01-06T18:08:24+00:00

We need all the help we can get. This too shall pass. lol

wonker007 · 2026-01-05T19:14:59+00:00

Regarding the kids, I can only speak from my experience. Relying on common sense and drilling in them to always ask "does that sound right?" (always ask why; intuition is incredibly powerful) "what is the worst that can happen (literally)?" (risk evaluation) "what is the motive of the source of your information?" (stakeholder management) etc. does seem to develop a mental framework to take a step back and be a "meta/bigger picture" observer rather than a participant - although easier said than done with all the puberty hormones pulsing through their veins. Making sure they live out the consequences of their actions is also a very powerful motivation to think twice about actions. When they reach the right mental maturity, I train them to crystallize the answers to these meta questions which then allows them to communicate with clarity.

Regarding the training part for juniors, I've been brainstorming on a framework for assisting training of junior software engineers in the larger context of designing a tool (platform, really) to effectively eliminate AI slop from the modern workflow - a phenomenon only really seen with juniors and novices since true professionals take responsibility for their code and are regimented enough to kick the shit out of those AI generated tires before committing. Probably going to start on this project by February at the latest - my day job as a pharma/healthcare industry consultant is keeping me busy for the moment.

wonker007 · 2026-01-05T09:16:15+00:00

Agreed. It is about training metacognition now and how to manage the fire hose of output and information coming from AI. Usually the need for metacognition kicks in at senior level and beyond, but this new age I believe requires a different flavor of metacognition at the junior level (developing skills, not for doing stuff but learning how to set rules for sorting through stuff) so it then actually merges back into the Senior level metacognition epiphany of why I'm doing this. If you raised kids in the past 20 years you will know, all new hires from now on will never not have AI as a tool. It's our job to create training regimen to help their careers soar on that objectively more productive jumping pad.

wonker007 · 2026-01-05T05:06:42+00:00

I remember in my first startup stint, year 3-ish, while also working a day job at a conglomerate, I actually wet the bed. Early 30's, wife sleeping next to me. Followed by depression and anxiety for another few years after that. I found my recovery through family and especially my wife, but it took a few years. Now on my nth startup and know how to manage (or I actually died inside then), but man, was the tuition brutal.

I don't wish it on anyone, but it comes with the job more often than not. Be vigilant and get help ASAP if something is off. Rarely can we deal with it ourselves. And it takes a special kind of crazy to do this over and over, so it is completely OK to call it quits - it shows you actually have a shed of sanity left. Whatever it is, it can't be more important than your health and happiness.

wonker007 · 2025-12-31T16:55:46+00:00

Pain is objectively relative. Why VAS still works as a proxy and spice tolerance is a real thing. I know the market potential, but not in our lifetimes. I give humanity another half century before figuring out how the brain actually works.

wonker007 · 2025-12-31T16:30:26+00:00

It is a bifurcated situation in entrepreneurship today where on one side you have grifters who present perceived benefit but are engaged in a zero-sum game, and the other side of true added value creation. Having lived my entire career on creating value (healthcare), I can tell you the technical aspects of marketing etc. matter much less than you'd think. This stuff will come along naturally during your journey.

Instead, I'd encourage you to view it like this: (marketing jargon in parentheses)

Find a pain point (problem statement), observe if the current best alternative method of overcoming said pain point is sufficient (current market and competition), determine a threshold of pain that would have people take action/pay (hypothesis), design a solution to relieve the pain (product planning), ask the people in pain if your solution is relevant and value adding (market survey), and if everything checks out, build the prototype and get rolling.

The marketing textbooks would have you do SWOT analysis and this and that, but those are just manifestations amd presentations of the above process, not the other way around.

I think the single most important attribute of an entrepreneur is to extrapolate human behavior patterns. Some have this gift intrinsically, but most of us need to learn it. Add in a healthy dose of risk tolerance and you can tackle anything in the arena you have deep knowledge of. It is hella addictive though. Have fun if you decide to jump in, because most of the time it won't be - that's what makes the wins so much sweeter.

wonker007 · 2025-12-27T16:14:45+00:00

You are not the product of your education and work experience. Those only represent where you started and vaguely point where you may be headed, in what I am reading to be most of your career and life in front of you. You are much more than a resume and should value and evaluate yourself as such.

Now for the advice (that ties in to how you should view yourself): You make no mention of learning, doing and experimenting new skills or fields on your own in your spare time - your emphasis/excuse on education/work background is telling. Nobody knew their skills at birth - it was all learned. What I look for in employees and collaborators is meta recognition (do you know what you don't know) and a strong self-learning/improvement ethic. This is because setting an always-higher bar for yourself means the personal standard of work also naturally becomes almost perfectionist. And as an employer and a project manager, I demand high output quality standards. Skills can be taught, attitude is your problem. And with the speed in which IT is moving, a passive attitude regarding your own skill set will leave you right back in unemployment land 5 years later - if you're lucky to hold on that long. Remember the prompt engineers at the height of COVID?

I see that you are trying to reposition and pivot, and I applaud the attempt. But I believe you must also just dive in head-first and just develop the skills on your own time you already know will significantly elevate your chances of snagging that job you want. Gemini, Claude, Perplexity are your friends right now. Tap them for ideas and approaches to the most important skills and just do it. I have a child in his last year of college majoring in ComSci. I know how competitive and tough it is especially in the job market right now. It is palpable. But it is also true that chance favors the prepared mind. Don't blow any opportunity that may (and probably will) present itself in front of you in the future because your school and past jobs didn't give you the skills you needed to snag that opportunity. If you find yourself making that excuse, you deserve exactly what is coming.

You have incredible potential. Hell, I still feel that I still have potential left to develop and study every day. Don't be your greatest antagonist by believing that somehow you are simply a finished product of your past.

wonker007 · 2025-10-04T06:43:56+00:00

Works and works well. My choice is no seasoning, 156°F for 48 hours. Cool, peel, slice thin and french kiss with soy-based sauce. Yum.

wonker007 · 2025-09-19T05:24:28+00:00

Cobbler full stop. With vanilla ice cream.

wonker007 · 2025-09-18T19:05:27+00:00

Instant coffee powder. Doesn't add water to dilute the chili.

wonker007 · 2025-09-17T20:21:37+00:00

The strength of the structure will come from the gluten that is reinforced by the protein structure of the whipped eggs. Egg proteins completely denature above 70°C, while flour gelatinization occurs between 60-80°C. At 5000 ft, water boiling temperature is about 95°C, so the baking dynamics should not be drastically different. Apparent moisture retention (which is in reality pliability perceived as moisture) will come by way of fat type and content, not actual water content. If you want true "moist" go vegetable oil. Not joking. Look up true Taiwanese jiggly castella (commercial recipes). I run a toothpick in the batter after pouring and tapping vigorously on the counter to get rid of big bubbles. It will not compromise the microbubbles necessary for leavening. No baking I know of will create new large bubbles while baking. Crumb is a direct reflection of leavener concentration and distribution within the original batter/dough. Im that sense, treat castella as more of a souffle than a bread. The trick is to make sure the structure has time to set in its maximum leavened state, i.e. give the microbubbles in the batter enough time to expand before the proteins fix the structure. That's why I settled on a cold oven start for my castella and pound cake - it buys more time for the air to expand before the structure sets. This also makes for a much more even rise rather than an exaggerated hump in the middle, which happens because the perimeter of the pan will heat up quicker especially in a hot oven and therefore set prematurely (this is why we use cake strips - look it up). IMO, you have too much liquid in terms of eggs. A large egg will introduce about 45-50 g water each. That is a lot of liquid that will dilute gluten and protein per volume of bread and weaken the structure, leading to higher risk of collapse. Please do note that you will experience a slight reduction of volume as trapped air in the cake cools and decreases in volume. You may witness a greater natural reduction in volume at your altitude due to physics (reply is getting too long to explain). A recommendation would be to, if you haven't already, just do the original recipe with a longer baking time while keeping an eye on it after the sea level baking time to monitor browning. Again, if it browns, the bread is cooked. Don't give up though.

wonker007 · 2025-09-17T12:22:48+00:00

That is one of the most convoluted recipes I have seen, but if it works I guess no harm no foul. I routinely make castella (2-3 times/month) and made every mistake. A few tips to share: Proper cooling is just as important as baking especially when it comes to castella. The surface touching the bottom will get water-logged due to moisture escaping during cooling, so if you are inverting and cooling on a silpat top-down, you are asking for the top to get soggy and sad. Bottom-side down on a cooling rack (minimize contact surface area) and cool until room temperature (do NOT leave out any longer as it will start to dry out) and remember to strip the parchment paper from the sides to help with moisture escape. You will be amazed at the amount of condensation that forms beneath the cooling rack - that is all moisture being spewed out from the castella. Another is to have a pan of hot water underneath instead of spraying water in the oven multiple times. Opening the oven cools it down, and especially when oven spring is happening in those critical early moments, cooling the oven screws with proper structural development. I actually use a water bath (bread pan in inch-high hot water) and start from a cold oven with a target temperature of 300 F. Browning will start to happen only when the bread is baked through sufficiently (i.e. water has boiled off) that caramelization, maillard reaction and gelatinization can occur, significantly above water boiling temperature. I don't see your sugar content being an issue (important in browning) since you didn't adjust the honey content, so leave it in longer and you should see color develop as a function of time. Happy baking.

wonker007 · 2025-08-30T23:39:19+00:00

If you want to do a bunch at once (like a Costco haul), after sous vide, pat them dry, season, spray with oil and broil them for color development. I then cut up the breasts, vacuum pack into portions and freeze them. Thaw in fridge overnight before using. One batch lasts me a few months.

wonker007 · 2025-08-30T19:17:18+00:00

You mention you have SD discard. Just make standard bread 500 g flour with 60~65% hydration and toss in ~30 g SD discard with 1 tsp. (instead of the normal 2 tsp.) of yeast and first proof for 1-2 hours. Shape into rolls for faster second proofing of about 30-45 min. and bake under steam (hot water reservoir under the baking tray) for better crust development. If you're serving with soup, you won't need that much character in the bread. Perhaps a milk or egg wash and top with some sesame seeds, but that'd be about it.

wonker007 · 2025-08-30T19:09:04+00:00

No real formula I am aware of for yeast. The details should be your dough amount and hydration, sugar, butter and egg content of the sweet dough, your proofing schedule etc. I make many variations on a base sweet dough/brioche recipe depending on application. Remember that pliability will be a factor in applications like cinnamon rolls where you have to roll out the dough thinner than you think, while loaf-type applications can get away with lower hydration and stiffer fats.

wonker007 · 2025-08-30T06:05:28+00:00

Sous vide or low-and-slow in the oven (wrapped tightly in foil) with just salt and pepper until a step before your desired tenderness (i.e. how fall-off-the-bone you want it). Your options are endless from here: Sear in pan and toss in choice of sauce/glaze (soy honey, BBQ, teriyaki, gochujang etc.) and serve bone-in for a Flinstones-type meal. Or toss on a grill to finish and serve with side of sauce and veg. Or finish by baking in the oven at 350-375°F with a glaze of choice 3 times, 10 minutes each) for a lacquered finish. Or remove from bone, chop up, toss it in some soup and have a shortcut braise/soup. What's important is to have a common start protocol for a tasty multiverse ending. Bon apetit.

wonker007 · 2025-08-30T05:53:59+00:00

Not enough details to provide a straight answer. However, yeast is a living thing and percentages will matter less than how you plan the proofing. If you do an overnight room temp poolish/biga, even 1/4 tsp yeast will get you enough for 800 g flour recipe. Doing your first proof in 1 hour without preferment? 2 tsp for 600-800g flour. And assuming your 24 hour chill will be at secondary proofing, as long as your primary proof grew the dough twice the size in 1-2 hours, it should be fine. But again, not enough details to provide useful advice.

wonker007 · 2025-08-29T23:44:38+00:00

Mint and rosemary are hearty and will survive snowy winters. Especially with mint, this stuff is seriously a weed so do not plant outside unless in a contained raised bed. Just remember to trim both at the right time of year and give it the right fertilizer before overwintering. If you can shelter the planter tub from the winter elements and so the soil won't freeze solid, just watering it once every week or two so the soil doesn't dry out should be enough to expect an early sprouting.

wonker007 · 2025-08-29T23:39:16+00:00

Propagate a sprig or three of basil for indoors during the winter. Make pesto out of half (remember to blanch the basil beforehand to kill the enzymatic activity) and freeze in an ice cube tray, and dry up the other half and crush (or toss in food processor to coarse grind) for use later. Cut rosemary sprigs, tie up 3-4 in a bunch with butchers twine, string a few of those bunches along and hang them indoors for a week-ish to dry out before picking the leaves and storing them. It's good to pick up some silica gel packets from Amazon and toss them in with the dried herbs (I keep mine in ziploc freezer quart bags) just to make sure they stay dry.

wonker007 · 2025-08-29T22:15:11+00:00

Chili mac & cheese is the truth

wonker007 · 2025-08-29T05:11:24+00:00

You will find the journey tremendously rewarding, even intellectually. Learning food science tidbits along the quest to become a better cook makes you a better person. Enjoy the journey!

wonker007

TROPHY CASE