4 ms·

We've collected a number of the various Cas variants into Pinecone if anyone wants to play around with the proteins [1]. In this article they speak of cheap de

We've collected a number of the various Cas variants into Pinecone if anyone wants to play around with the proteins [1]. In this article they speak of cheap detection, but in some sense those are the natural technological requirements or outcomes of their much more powerful editors (you have to be able to 'see' the results of what you've edited in order to more efficiently edit). In order to better edit, nice readouts were required to be invented. The Cas systems are 'pointers' or 'cursors' to locate a specific sequence of DNA or RNA - and once you have a good pointer, you can bring to bear all the rest of biology's tricks at that location. Multi-fluorophore systems are great, and gels are easy. It's a super creative effort to utilize those cheap reagents and assays in the context of a creative 'DNA locator' system in order to amplify a single genomic signal to one that is readable by eye, in the field. And that capability makes the debugging of the editors themselves at the more cheap and easy. Our collective 'toolkit' is now becoming complete enough that the creative and combinatorial usage of existing tools will very quickly explode our capabilities. YC's own Benchling also has the sequences (and is cited in the papers' supplements): https://benchling.com/s/seq-arzpsupZEzGu3ghBDhtv/edit https://benchling.com/s/seq-arzpsupZEzGu3ghBDhtv/edit (Shame on Science Magazine for publishing a supplemental PDF with Benchling links that you cannot click on and sequences that are not copyable (pg 24). It's 2018!: http://science.sciencemag.org/content/sci/suppl/2018/02/14/science.aar6245.DC1/aar6245_Chen_SM.pdf http://science.sciencemag.org/content/sci/suppl/2018/02/14/s... (and Benchling, if your target audience is printing out links, you might want to not use both O and 0 in your UIDs)) Our protein based design software: [1] https://serotiny.bio/pinecone/ https://serotiny.bio/pinecone/ (search Cas13, REPAIR)

JumpCrisscross 9y ago
What is Pinecone? Can I hack around with it as an individual?
- jfarlow 9y ago
  Pinecone is our public protein design software. Feel free to play around. Feedback is welcomed. We're trying to build an abstraction layer above DNA sequences so you can build genetic tools to fulfill particular capabilities without needing to know how to build DNA. Or just to help teach what useful designs others have put out there - reveal some of the 'magic' of current gene therapies or genetic editing tools. Some interesting examples: https://serotiny.bio/notes/proteins/ https://serotiny.bio/notes/proteins/
  - JumpCrisscross 9y ago
    Neat! What sorts of design decisions did you have to confront when designing this language? Have you found it useful as a toy modelling space, i.e. where suitably replicating real-world protein X in “code” reveals interesting things about X?
    - jfarlow 9y ago
      A bit of a late reply, sorry, but it's a great question. We found many design decisions we had to confront - more than we expected. The largest two include 1) the decision to use an amino acid sequence as ground truth (and not DNA), and 2) the decision to make the language universally proscriptive (at the cost of being universally descriptive). Anything you build in the system can be altered, broken apart, and itself be part of a larger whole - all while being manufacturable. But that comes at the cost that there are certain highly complicated overlapping synergistic type designs that just can't be made. Whereas with an entirely descriptive language one can describe the multi-layered fugue that is the HIV genome - but the construction rules become so lax that they lose their instructive capabilities, and can no longer logically guarantee constructibility. The most interesting (and surprising?) thing we learned is that we now have the only data-structure that can reliable and efficiently answer questions of the sort of, "show me any/all designs that utilize the protein, _GFP_".

JumpCrisscross 9y ago

What is Pinecone? Can I hack around with it as an individual?

jfarlow 9y ago
Pinecone is our public protein design software. Feel free to play around. Feedback is welcomed. We're trying to build an abstraction layer above DNA sequences so you can build genetic tools to fulfill particular capabilities without needing to know how to build DNA. Or just to help teach what useful designs others have put out there - reveal some of the 'magic' of current gene therapies or genetic editing tools. Some interesting examples: https://serotiny.bio/notes/proteins/ https://serotiny.bio/notes/proteins/
- JumpCrisscross 9y ago
  Neat! What sorts of design decisions did you have to confront when designing this language? Have you found it useful as a toy modelling space, i.e. where suitably replicating real-world protein X in “code” reveals interesting things about X?
  - jfarlow 9y ago
    A bit of a late reply, sorry, but it's a great question. We found many design decisions we had to confront - more than we expected. The largest two include 1) the decision to use an amino acid sequence as ground truth (and not DNA), and 2) the decision to make the language universally proscriptive (at the cost of being universally descriptive). Anything you build in the system can be altered, broken apart, and itself be part of a larger whole - all while being manufacturable. But that comes at the cost that there are certain highly complicated overlapping synergistic type designs that just can't be made. Whereas with an entirely descriptive language one can describe the multi-layered fugue that is the HIV genome - but the construction rules become so lax that they lose their instructive capabilities, and can no longer logically guarantee constructibility. The most interesting (and surprising?) thing we learned is that we now have the only data-structure that can reliable and efficiently answer questions of the sort of, "show me any/all designs that utilize the protein, _GFP_".