E. Coli Whole Cell Model by Covert Lab Updated +Created
github.com/CovertLab/WholeCellEcoliRelease is a whole cell simulation model created by Covert Lab and other collaborators.
The project is written in Python, hurray! But according to te README, it seems to be the use a code drop model with on-request access to master, very meh, asked rationale on GitHub discussion, and they confirmed as expected that it is to:
  • to prevent their publication ideas from being stolen. Who would steal publication ideas with public proof in an issue tracker without crediting original authors?
  • to prevent noise from non collaborators. They do only get like 2 issues as year though, people forget that it is legal to ignore other people :-)
Oh well.
The project is a followup to the earlier M. genitalium whole cell model by Covert lab which modelled Mycoplasma genitalium. E. Coli has 8x more genes (500 vs 4k), but it the undisputed bacterial model organism and as such has been studied much more thoroughly. It also reproduces faster than Mycoplasma (20 minutes vs a few hours), which is a huge advantages for validation/exploratory experiments.
The project has a partial dependency on the proprietary optimization software CPLEX which is freeware, for students, not sure what it is used for exactly, from the comment in the requirements.txt the dependency is only partial.
This project makes Ciro Santilli think of the E. Coli as an optimization problem. Given such external nutrient/temperature condition, which DNA sequence makes the cell grow the fastest? Balancing metabolites feels like designing a Factorio speedrun.
There is one major thing missing thing in the current model: promoters/transcription factor interactions are not modelled due to lack/low quality of experimental data: github.com/CovertLab/WholeCellEcoliRelease/issues/21. They just have a magic direct "transcription factor to gene" relationship, encoded at reconstruction/ecoli/flat/foldChanges.tsv in terms of type "if this is present, such protein is expressed 10x more". Transcription units are not implemented at all it appears.
Everything in this section refers to version 7e4cc9e57de76752df0f4e32eca95fb653ea64e4, the code drop from November 2020, and was tested on Ubuntu 21.04 with a docker install of docker.pkg.github.com/covertlab/wholecellecolirelease/wcm-full with image id 502c3e604265, unless otherwise noted.
Multiomics Updated +Created
Integrating multiple omics, comes quite close to whole cell simulation.
Never trust an experiment that is not supported by a good theory Updated +Created
Not the usual bullshit you were expecting from the philosophy of Science, right?
Some notable quoters:
Ron Maimon Updated +Created
Ron Maimon is a male human theoretical physicist with an all but dissertation started in 1995 at Cornell University[ref][ref].
Figure 1.
Ron Maimon's Physics Stack Exchange profile picture
. Source.
Ron is mostly known for simultaneously:
Ron seems to share a few philosophies which Ciro greatly agrees with as part of Cirism, which together with his knowledge of physics, make Ciro greatly respect Ron. Such philosophies include:
However he also subscribes to some theories which Ciro Santilli considers conspiracy theories, e.g. his ideas about the Boston Marathon bombing that got him banned from Quora (a ban which Ciro strongly opposes due to freedom of speech concerns!), but the physics might be sound, Ciro Santilli does not know enough physics to judge, but it often feels that what he says makes sense.
chat.stackexchange.com/transcript/message/7104585#7104585 mentions that he was at Cornell University and did all but dissertation, but he mentions that he was still self-taught:
Eugene Seidel: On your personal info page you write that you are not a physics Ph.D. but does that mean you were a physics undergrad in college then went to grad school and finished ABD... or are you entirely self taught?
Ron Maimon: ABD. I am self- taught though, I only went to school for accreditation. I had a thesis worth of work at the time I left grad-school,
Eugene Seidel: ok thanks
Ron Maimon: I was just kind of sickened by academic stuff that was going on--- large extra dimensions were popular then.
Eric Walker: Anyway, thanks Ron -- I'll get back to you with more questions soon, I'm sure.
Ron Maimon: Also I was at Cornell, my advisor left for Cincinnatti, and I was not in very good standing there (I was kind of a jerk, as I still am). Some friends wanted to start a biotech company called "Gene Network Sciences", and I joined them.
This is corroborated e.g. at: web.archive.org/web/20201226171231/http://pages.physics.cornell.edu/~gtoombes/Student_Index.html (original pages.physics.cornell.edu/~gtoombes/Student_Index.html down as of 2023).
At youtu.be/ObXbKbpkSjQ?t=2454 from Video 1. "Ron Maimon interview with Jeff Meverson (2014)" he mentions his brother is a professor. At physics.stackexchange.com/questions/32382/could-we-build-a-supercomputer-out-of-wires-and-switches-instead-of-a-microchip confirms that his brother's name is "Gaby Maimon", so this neuroscience professor at the Rockerfeller University is likely him: www.rockefeller.edu/our-scientists/heads-of-laboratories/985-gaby-maimon/. Looks, age, location and research interest match.
Bibliography:
  • gmachine1729.livejournal.com/161418.html Ron Maimon answers about physics and math on Quora (part 1) by Sheng Li (2020) contains a selection of some amazing Ron Maimon posts
  • www.reddit.com/r/RonMaimon/ someone made a Reddit for him. Less than 100 users as of 2022, but has potential.
  • some Quora threads about him, oh the irony:
    • www.quora.com/Is-Ron-Maimon-actually-a-pioneer-or-a-jest
    • www.quora.com/Are-Ron-Maimons-answers-on-mathematics-physics-and-computer-science-factually-correct
    • www.quora.com/What-do-people-think-of-Ron-Maimons-paper-Computational-Theory-of-Biological-Function-I
    • www.quora.com/Who-is-Ron-Maimon/answer/Ron-Maimon
      I'm a physics grad school drop-out working in theoretical biology but I still do physics when I get a chance, but not right now because I am in a middle of a project to understand the properties of a certain virus as completely as possible.
      Also in a comment he explains something to a now deleted comment, presumably asking why he dropped out of grad school, and gives a lot more insight:
      It's a complicated boring story.
      I dropped out mainly to do biology with friends at a startup, because I figured out how you're supposed to do theory in biology, but also I truly believe it was next to impossible for me to get a degree without selling out, and I would rather be shot than write a paper with an idea I don't believe.
      My grad school phase was a disaster. I first worked for Eric Siggia, but I got away because he had me do something boring and safe, I figured I have only a limited number of years before I turn 30 and my brain rots, and I wasn't going to sell out and do second-rate stuff. I found a young guy at the department doing interesting things (Siggia was also doing interesting things, like RNA interactions, he just wouldn't assign any of them to ME), this was Philip Argyres, and got him to take me. Argyres wanted me to work on large-extra dimensions (this was 1998), but I made it clear to him that I would rather be boiled in oil. I worked a little bit on a crappy experimental setup that didn't work at all, because I didn't know enough about electromagnetic screening nor about how to set up experiment. But EVERYONE LOVED IT! This is also how I knew it was shit. Good work is when everyone hates it. But I learned Lifschitz's ideas for quantum electrodynamics in media from this project.
      Me and every competent young person in high-energy physics knew large extra dimensions was a fraud on the day it came out, and I had no intention of doing anything except killing the theory. Once Wikipedia appeared, I did my best to kill it by exposing it's charlatanry on the page for large extra dimension. That was in 2005 (after getting fired from the company), and from this point onward large-extra-dimensions lost steam. But I can't tell how much of this was my doing.
      Argyres liked N=2 theory, and we did something minor in N=2 SUSY models around 2000, but I was bogged down here, because I was trying to do Nicolai map for these, and it ALMOST worked for years, but it never quite worked. But I knew from the moduli interpretation and Seiberg-Witten solution that it must work. If I live long enough, I'll figure it out, I am still sure it isn't hard. But this was the link to statistical stochastic models, the work I was doing with Jennifer Schwarz, and I wanted to link up the two bodies of work (they naturally do through Nicolai map).
      But I had my own discovery, the first real discovery I made, in 1999, this thing that I called the mass-charge inequality, what Vafa and Motl called "the weakest-force principle" when they discovered it in 2006. It was swampland, and Vafa hadn't yet begun swampland. My advisor didn't believe my result was correct, because he saw me say many stupid things before this. So he wouldn't write it or develop it with me (but I had read about Veltman telling 'tHooft he couldn't publish the beta-function, I knew Argyres was wrong about this)
      Anyway, Argyres left for Cincinnatti in 2000, and I joined the company then. I was in the company until january 2005. Then they fired me, which was ok, by then it was a miserable hell-hole full of business types.
      I discovered Wikipedia, and started killing large extra dimensions. I wanted to finish my thesis, and some people agreed to help me do this, but I had told myself "no thesis until you get the Nicolai map sorted out" and I never did. I worked with Chris Henley a little bit, who wanted me to do some stuff for him, and I discovered an interesting model for high-Tc, but Henley said it was out of fasion, and nobody would care, even though I knew it was the key to the phenomenon (still unpublished, but soon).
      This was 2008-2009, and I became obsessed with cold fusion, so Henley dropped me, as I had clearly gone crazy. I developed the theory of cold fusion during the last weeks of working for Henley. Then I dropped out for good.
      Honestly, by the time I was gone, I realized that the internet would make a degree counterproductive, because I knew I had better internet writing skills than any of the old people, I was a Usenet person. Online, the degrees and accreditation were actually a hinderance. So by this point, I secretly preferred not to have a PhD, because I knew I was good at physics, and I could attack from the outside and win. It's not too hard if you know the technical material.
      The only problem is that I was unemployed and isolated in Ithaca for about 7 years after having gone through my first productive phase. But I developed the cold-fusion ideas in this period, I learned a lot of mathematics, and I developed a ton of biology ideas that are mostly unpublished, but will be published soon. It astonished people that I could have no degree and be unemployed and have such a sky-high ego. The reason is that I could evaluate my own stuff, and I liked it!
Backlinks:
Video 1.
Ron Maimon interview with Jeff Meverson (2014)
Source. Ripped from Jeff's "Quoracast": player.fm/series/quoracast-podcast/ron-maimon-truther Ron mentions he was an early-Usenet user. Key points:
Systems biology Updated +Created
Studies biology from a more global point of view, if putting all little pieces of an organism make up the final biological function.
Whole cell simulation Updated +Created
Ciro Santilli started taking some notes at: github.com/cirosantilli/awesome-whole-cell-simulation. but they are going to be all migrated here.
It is interesting to note how one talks about single cell analysis, in contrast to whole cell simulation: experimentally it is hard to analyse a single cell. But theoretically, it is hard to simulate a single cell. This mismatch is perhaps the ultimate frontier of molecular biology.
Video 1.
A Computational Whole-Cell Model Predicts Genotype From Phenotype by Markus Covert (2013)
Source.