8 ms·
Biochemical Pathway Maps
- Kim_Bruning 5y agoPeople sometimes ask me how come a biologist might end up programming (or vice versa). Showing them a map like this tends to clear things up pretty quickly!
- hprotagonist 5y agoyeah, but the programmer will believe the chart. the biologist, who knows better, will regard the chart as “our current best attempt at documentation, subject to change at any time at all” My background is biomedical. This or a very similar chart was used in the last week of lectures on control systems as a lesson in humility. It was meant to demonstrate both how complex things can be — and then, when the professor recolored the lines on a section according to the confidence in their correctness as a function of recent research, how uncertain our knowledge of that complexity really is. He had a backup slide where an entirely new graph, with almost no topological similarity to the metabolic one, was created for a few of the nodes that participate in other nonmetabolic pathways.
- jostmey 5y agoAgree with you 100%. This chart is just barely scratching the surface
- Kim_Bruning 5y agoIt's a pretty cool field!
- cameronh90 5y ago"the programmer will believe the chart." I see you've not done much legacy software maintenance.. ;)
- grishka 5y ago> yeah, but the programmer will believe the chart. I'm a programmer and I do understand that these maps are "as much as we currently know" and the "we currently know" is expanding rapidly. I like to see biology as reverse engineering alien technology made by a much more advanced civilization. Of course that's not true — it all evolved over billions of years — but the resemblance is totally there. The one thing that really strikes me about biology is how young of a science it actually is and how much progress we've made in so little time. It was only 1953 when the structure and function of DNA was discovered. In terms of history, it's not even yesterday. Yet now, 68 years later, we're literally injecting people with correctly encoded instructions to make a harmless part of a deadly virus to save their lives. This kinda blows my mind.
- hprotagonist 5y ago>I like to see biology as reverse engineering alien technology made by a much more advanced civilization. Of course that's not true — it all evolved over billions of years — but the resemblance is totally there. Be really careful here, though, otherwise you'll hoodwink yourself. The two famous things that come to mind for me are these, both of which remind me to tread carefully: https://blogs.sciencemag.org/pipeline/archives/2007/11/06/andy_grove_rich_famous_smart_and_wrong https://blogs.sciencemag.org/pipeline/archives/2007/11/06/an... https://www.cs.utexas.edu/users/EWD/transcriptions/EWD09xx/EWD936.html https://www.cs.utexas.edu/users/EWD/transcriptions/EWD09xx/E...
- dekhn 5y agomost of the edges in this graph were elucidated using radiocarbon tracking, and they are generally well-established. I don't think there have been major corrections to the Calvin cycle in 50 years. Ditto for the glycolysis cycle- at best, people find alternative paths and excursions, but they're not on-path for core biology. These metabolic charts, like the results of spectroscopy, actually represent some of the best, highest quality scientific reference data that exists.
- deleted 5y ago[deleted]
- acchow 5y agoI don't ever see anything nearly this complex in software. Programming has encapsulation/boundaries. In biology, everything can have an effect on everything else (with side channels appearing everywhere, even having influences via thermodynamic laws, pH, etc).
- Kim_Bruning 5y agoEh? There's quite some encapsulation in biology too. Often literally. But yeah, subsystems don't need to be kept to a size that will fit inside a regular programmer's working memory.
- ta988 5y agoYes and there are also the non enzymatic reactions that the genetics-focused people tend to ignore, but they have a big importance on a metabolome and its evolution over time after extraction.
- etiam 5y agoRelated discussion from about 6 months back (including where to find the PDF version). https://news.ycombinator.com/item?id=25158249 https://news.ycombinator.com/item?id=25158249
- deleted 5y ago[deleted]
- splittingTimes 5y agoEven earlier discussion, also with Link to posters in discussion https://news.ycombinator.com/item?id=23448398 https://news.ycombinator.com/item?id=23448398
- Nohortax 5y agoI didn't know such map exists. I wonder if I can get one as a poster !
- detaro 5y agohttps://www.roche.com/sustainability/philanthropy/science_education/pathways/pathways-ordering.htm https://www.roche.com/sustainability/philanthropy/science_ed... EDIT: and see hint below for pdf: https://news.ycombinator.com/item?id=27545148 https://news.ycombinator.com/item?id=27545148
- Nohortax 5y agoThank you ! I've just ordered it. I hope I'll receive it :)
- newbie789 5y agoI love these posters! I had them on my bedroom wall as a teenager. (I had very little idea about most of what it is describing, but I thought it looked cool and hey, it’s free!)
- Nohortax 5y agoPretty cool !! I just ordered mine on their website. They provide it in two parts : 1. Metabolic Pathways (139cm x 98cm / 4.5feet x 3 feet) 2. Cellular and molecular processes (115cm x 98cm / 4feet x 3feet)
- PragmaticPulp 5y agoThese maps are fun and fascinating, but can be misleading for the supplement enthusiasts. In many cases you can trace pathways upstream until arriving at a supplement or nutrient that can be bought online. People erroneously assume that consuming that nutrient will achieve some downstream effects in certain pathways because all of the arrows connect. It's not that simple, though. For the most part our bodies are excellent at absorbing the nutrients we need and regulating everything as appropriate.
- zaking17 5y agoIt’s cool to see this on HN. It’s a common activity in metabolic modeling & metabolic engineering circles to build new pathway visualization tools (I spent a chunk of my PhD on one called “Escher”). I keep waiting for a tool to come along that’s good enough to be sticky and win this little market. But it might be more like IDEs, where there are some classics (pathway tools = emacs?), and an endless supply of new entrants.
- ta988 5y agoPeople have tried that, but the problem is that every group have their tools in different languages, different flow management systems etc
- joshuamcginnis 5y agoFor the last year, I've been self-learning synthetic biology by working to become one of the few people to have ever genetically modified fungi in a diy lab environment[1][2][3]. It occurred to me that genetic engineering is largely a process of hacking biosynthetic pathways; that is, we take heterologous genes from organisms which have evolved novel biochemical pathways and we put them into other organisms that are really good at biosynthesizing those compounds at-scale (like Saccharomyces cerevisiae aka yeast). One thing I've observed is there seems to be no universal well-annotated structured database for biosynthetic pathways. Updates and additions to known pathways are published unstructured in papers, often in graphical form, presenting even more challenging for structuring the data. Were this to exist, it would be possible to build an app that let you easily design DNA plasmids for testing all kinds of incredible biosynthesis experiments. For instance, it would be able to select an organism [E. coli], enter your starting substrate [glucose], select a desired metabolite [psilocybin] and out would come a DNA sequence for a plasmid that contains are the necessary parts, promoters, genes and terminators for transforming E. coli to produce psilocybin. In my opinion, such a tool could profoundly impact science, industry and human well-being. [1] http://everymanbio.com/ http://everymanbio.com/ [2] https://www.instagram.com/everymanbio/ https://www.instagram.com/everymanbio/ [3] https://youtube.com/everymanbio https://youtube.com/everymanbio
- ddxxdd 5y agoBefore I start binging on every single aspect of your social media, I gotta know: Have you tried applying your hobby towards reducing the cost of healthcare in America? Could you somehow make monoclonal antibodies in your petri dishes? Could you diagnose what kind of flu virus you have? Because the phrase "self-learning synthetic biology" immediately rang a bell inside my mind that screamed "small business dedicated to cheaper healthcare", and is something that I have considered dedicating my free time towards.
- joshuamcginnis 5y ago> Have you tried applying your hobby towards reducing the cost of healthcare in America? That isn't my stated goal, but I would imagine that sharing how to genetically engineer an incredibly powerful organism to express heterologous genes for less than $3000 in a kitchen lab could open up many possibilities! > Could you diagnose what kind of flu virus you have? Is it possible to extract DNA from a bodily fluid, perform PCR and read the sequence results to determine flu variant? I'd have to check on if there is a known DNA sequence that barcodes flu viral variants, but presuming there is, then yes - all of this is possible from a home lab currently.
- marstall 5y agoI remember reading someone doing the math on these and finding that statistics-wise, it was essentially impossible for these metabolic pathways to have evolved through randomness given the age of our planet.
- gus_massa 5y agoAll the calculations that I've seen with similar claims are very wrong. Do you have a link so I can take a look? Just an important detail. It's not just randomness. It's randomness + natural selection.
- marstall 5y agoIt was part of the book, Arrival of the Fittest. The author somehow quantified the scale of the space of all possible chemical reactions and it was just so huge that the chance of the citric acid cycle emerging was just infinitesimal, like 1 in 10^100 or something. Like winning the lottery 10 times in a row type of thing. Found it an intriguing idea. Would be curious to see the counter argument, though it's likely to be beyond me mathematically.
- dav 5y agoWould be great to have a citation on this
- FredPret 5y agoThis chart is exactly the hacked-together kluge I expect of a randomly evolved solution. Keep in mind that as soon as an element is added to the system - and it works - that element becomes sticky. Rinse and repeat, and you get more and more complex systems over time.
- dekhn 5y agoi had this poster on my wall (actually, the predecessor, which you could order for free by physical mail) my entire sophomore year while taking biochemistry. I used to joke to people that by the end, I would have memorized most of it, and that did actually turn out to be true. Even today, some 28 years later, I remember the hexose mannophoshate shunt.
- flobosg 5y ago> which you could order for free by physical mail This one can be ordered as well.
- grkvlt 5y agoand here [0] is where you can order it. you can ask for paper copies of the poster to be mailed to you (free) from the roche philanthropy department! it took about a month for mine to arrive, i think, but they're really awesome looking and i now have the 'cellular and molecular processes' one hanging behind me in my front room, so that i look impressively clever on zoom calls ;) 0. https://www.roche.com/sustainability/philanthropy/science_education/pathways/pathways-ordering.htm https://www.roche.com/sustainability/philanthropy/science_ed...
- bainsfather 5y agoI ordered one about 1 year ago, but never received it. Possibly because I didn't have a 'proper' organisation (e.g. a university dept) that I could list in the form.
- grkvlt 5y agoi simply listed my perfectly ordinary residential flat's address in the uk. and, as far as i can tell from the text in the link i gave above, they are giving these away to anyone who wants one as an educational public service, hence the fact that it's the philanthropy department that runs the scheme. > We believe all people should have access to important scientific information to help their research and education. [...] Roche provides copies as a free service to the public. they are pretty cool to have, with very high quality two colour printing, and you also get a wee booklet with an index to the two posters to help you find things. there's also a book [0] by the same author with much more detail, and obviously much more portable, but sadly much more expensive ;( so, i'd try asking for them again, if i was you. 0. https://blackwells.co.uk/bookshop/product/9780470146842 https://blackwells.co.uk/bookshop/product/9780470146842
- sarak12070 5y agoBest trouser deal with complete review https://topsaleproductsonline.blogspot.com/2021/06/what-are-peg-trousers-with-best-deal.html https://topsaleproductsonline.blogspot.com/2021/06/what-are-... Interesting facts about black swallower fish I am sure you don't know https://www.interestingnews.club/2021/06/interesting-facts-about-black-swallower.html https://www.interestingnews.club/2021/06/interesting-facts-a... Woodpecker destroys nature camera at Russian nature reserve https://www.interestingnews.club/2021/06/woodpecker-destroys-nature-camera-at.html https://www.interestingnews.club/2021/06/woodpecker-destroys...
- xwdv 5y agoHow do I begin to understand this? Where do you start?
- JabavuAdams 5y agoMIT 7.016 Introductory Biology, Fall 2018 https://www.youtube.com https://www.youtube.com /playlist?list=PLUl4u3cNGP63LmSVIVzy584-ZbjbJ-Y63 MIT 5.111 Principles of Chemical Science, Fall 2014 https://www.youtube.com/playlist?list=PLUl4u3cNGP63LOmB3_O0xbgZVZibxj4rb https://www.youtube.com/playlist?list=PLUl4u3cNGP63LOmB3_O0x... Textbooks (free PDFs available on gen.lib.rus.ec): Lehninger, Principles of Biochemistry https://www.macmillanlearning.com/college/ca/product/Lehninger-Principles-of-Biochemistry/p/1319228003 https://www.macmillanlearning.com/college/ca/product/Lehning... Molecular Biology of the Cell https://www.ncbi.nlm.nih.gov/books/NBK21054/ https://www.ncbi.nlm.nih.gov/books/NBK21054/
- JabavuAdams 5y agoCitric-Acid Cycle, Krebs cycle Glucose, Acetyl-CoA, Pyruvate, ADP, ATP, NAD+, NADH, NADP, NADPH
- COGlory 5y agoYou start with what you eat. There are three (four if you include drinking) main categories: Protein Carbohydrates Fat Your goal is to take reduced carbon (carbon bound to hydrogen) and metabolize it to oxidized carbon (carbon bound to oxygen). That process releases energy your cells can use. The problem with oxidizing carbon is that it creates toxic products ("free" electrons) and involves splitting atmospheric oxygen (O2) into O-, which is very reactive. So then you need a whole host of other pathways to contain that reactive compound. If you really want to understand it, follow the carbon as it comes in, and trace it through to CO2. That's the pathway, and everything else is to support that.
- JabavuAdams 5y agoThat is some fault-tolerant spaghetti code!
- ta988 5y agoAnd each kind of cell, life-stage of cell and its history will have an impact on what part of those mapping are really in use at a given time.
- narrator 5y agoThe conciseness of DNA coding for all that proteins do is almost beyond human intelligence in its subtly and obfuscation.
- colordrops 5y agoIt's not clear yet whether it's beyond our intelligence or not.
- deleted 5y ago[deleted]
- krackers 5y agoOn the commercial side of this is Elsevier Pathway studio [1] [1] https://www.elsevier.com/solutions/pathway-studio-biological-research https://www.elsevier.com/solutions/pathway-studio-biological...
- dsign 5y agoBeautiful! And complex from start to finish. I wonder what formalisms/representations are there to manage the complexity of metabolic pathways. For example, say that that figure is 100% accurate, and furthermore, "all metadata needed" in terms of reaction rates, etc. for each individual reaction is available. If one wants to stage an intervention (say, suppress the production of compound X without altering anything else significantly), what kind of program would be able to find a solution?
- peterhil 5y agoMy friend who studied biochemistry in Turku University once had this kind of poster on his wall, but it had all the pathways overlaid on a human body. When I first saw it, I studied it for the better part of an hour. I have been trying to find an image of this poster without success. The detail level was like on these Roche posters, but the style was more like in these: https://www.tocris.com/literature/life-science-posters https://www.tocris.com/literature/life-science-posters
- qurashee 5y agoIt’s amazing how these things happen in the volume of a cubic micrometer. There is however a big misleading element; Not all of these pathways operate in the same cell and not all of them are equally strong - the arrows are not of equal “thickness” if you like. That’s the big problem in molecular biology and biochemistry: all these arrows are always depicted as of equal strength.