I can imagine that many experienced players rolled their eyes a bit when then saw the goal of ~100,000 submissions, thinking there was no way we could get so many players to generate so many solutions. But really, there is method in this madness. Hear me out. :-)
There are a total of 32 puzzles, most of which have a per-player limit of 150. That means each of us has a potential for submitting ~5000 solutions. I know of a handful of players who can actually do this with the tools they have available. Five players generating ~5000 designs comes to a total of ~25,000 designs, which is more than twice as many as we've ever had in the past, but it is still far short of 100,000.
How is it possible for a single player to create 5000 designs in two months? They don't all use the same techniques, but what they all have in common is having access to programs/scripts to do a lot of the heavy lifting of generating and/or evaluating possible designs. What I want to do is to make one or more of these automation tools accessible to 100 players, instead of only 5.
Here's an example that has been rolling around in my head the last few days. Say you have a design you think is promising. Maybe you created it, or maybe another player created. In either case, you bring it up in the game and decide on a way to experiment with variations. You mark the bases you would like to modify with the black marker, and load the Awesome booster from the booster menu. You then choose what kind of mutations you would like to see (mutations, deletions, ...) and what screening criteria (e.g. satisfies constraints with Vienna2) you would like applied. You click on a button and BOOM! you have a list of all the designs that satisfy your request.
At this point, you can choose to scroll through the designs to see how they look in the game and trim the list down as much as you want. When you are satisfied, you click another button to submit the remaining designs and ... (well it won't be BOOM!; maybe you should go take a nap) your computer will do that for you.
The floor is now open for discussion. Let the Force be with you.
I welcome this challenge to muster the players to step the game up a notch.
I can imagine two channels of discussions. One by players to propose tactics and choose a few for testing. One by coders to translate the tactics into code and provide feedback to the players if the coding process is not clear. The more clear the mission as defined by the players, the less coders and coding time would be required.
Hopefully, this post will:
1 Identify interested players.
2 get suggestions as to where channels of discussion should take place.
3 Define the mission of each channel with short timeline goals.
PS: The booster link above does not work. It says "could not get page block for ......"
I tried the link with and without the last backslash with the same result.
I have an idea that I think can help us players design our own experiments.
Really it is your idea, Omei. :)
I just transferred and rotated it a bit, just as if it was an RNA design. ;)
Science Template Across Labs
I had long been claiming that the FMN aptamer had a favorite orientation in relation to the switching area. I knew I was right as scores the new labs that had the FMN orientated as I wished to see it, seems to go in the right direction. But I didn't have a way to demonstrate in a short and easy manner so everybody would understand.
Omei demonstrated across different labs, how the different FMN aptamer orientation affected average fold change and max fold change. And put it in a easily viewable manner.
Science Template Inside a Single Lab
I think we can snatch that template and adapt it to designs in a single lab with different groups of experiments run against each other. (I even suspect the template could be automated later.)
I have put up a google doc with a couple of examples of how to shift Omei's overview for a lab round until something that can be used to test hypothesis in a single lab:
I also put up the labs and their links in a spreadsheet. One could also put up hypothesis like this.
Science Experiment Template
For those who haven't followed the related discussion, I have put up a collection of hypothesis I think is worth testing. Plus how to mark designs with hypothesis using # (Hashtags)
I will post my ideas on this tomorrow, but I will just say for now that I think it would function like foldit, only that instead of your score going up, you're number of designs will go up.
I'm attempting making an experimental plan that allows for running several hypothesis against a starter set of designs.
I am wondering if 15 designs against 15 designs are enough to gather reliable enough data for a comparison? Probably not.
I have tried structure it, so I can run two different aptamer positions in relation to MS2, in an exclusion lab (can be done for other than fmn labs). Then I would make two different sets, where one would have 1 long static stem and the other set would have two shorter static stems.
I would also like to test sets with if GU are present in the aptamer gate or not. Aptamer gate - the stem forming at the switching end of the aptamer, when the aptamer is bound to the molecule. This is to test that GU's are quite helpful in the aptamer gate - which I suspect.
Plan for 120 designs
All in all 4 experiments, testing 4 sets of hypothesis.
4 hypothesis, 4 pairs of 15 against 15 designs. Or 120 designs. For the GU test I would have 60 designs against 60.
However it may be better doing one less hypothesis but have space for more designs and getting better data. Silly me wishing for more slots. ;)
Alternative plan with 80 designs
You will be able to filter them via basic filters (base 50-65 matches the RY pattern you provide, Includes a specific sequence, etc.), or create your own (It's very basic scritpitng, so even in an in-game textbox).
I think of 2 more types of scripts:
1) Custom mutation (e.g- add a buldge of size 2, change a random A to G).
2) Series of mutations (e.g- mutate a random base -> Remove/Add a buldge -> maybe move the MS2 one base -> repeat). I do think the 2 types should be seperate, as that will allow type 2 to have a very simple graphical editor (with dropdowns for every type 1 script), but I'm not totally sure on that
one. We will have to plan more in order to decide.
Maybe type '1)' (and by extention type '2)') scripts could accept filters? For example Mutate the MS2 only to MS2 following the Strong/Strong/Weak ending (per eternac's comment here
Also, some questions:
- Does a query to submit a lab currently exist? If not I doubt it matters for now as for prototyping / early gathering a firebase server could be set up for now.
- You said that we can get 100k designs with this setup. However, do you think that duplication of designs won't be a problem? Especially if a lot of players start with the same sequence. Maybe we should use more than 24 versions of the MS2?
So I give it another go trying to set up an experiment plan.
Hypothesis: Are GU in switching area helpful or harmful to the switching ability of an RNA switch?
1a) One static stem, MS2 before second aptamer, with GU
1b) One static stem, MS2 before second aptamer, without GU
2a) One static stem, first aptamer sequence before MS2, with GU
2b) One static stem, first aptamer sequence before MS2, without GU
3a) Two static stems, MS2 before second aptamer, with GU
3b) Two static stem, MS2 before second aptamer, without GU
4a) Two static stem, first aptamer sequence before MS2, with GU
4b) Two static stem, first aptamer sequence before MS2, without GU
One hypothesis - potentially more insights gained
Things that could also be interesting to look out for related to this GU is beneficial in the switching area hypothesis:
On and OFF states may not benefit equally from a GU addition.
Exclusion and Same state designs may not benefit equally either.
Also in designs that holds a rotated aptamer, the rotated aptamer provokes a different solving style, GU’s may work different in there too.
Different states may differ in their need for GU’s.
However my suspicion that GU’s are a help to prepare a switching stem for switching and help it swap states. Not all GU’s everywhere in the switching area are expected to help. Some will worsen things.
Running the experiments
This could be run several ways:
One player could generate all the necessary designs much like in my Experiment plan and giving each design type 15 designs. (8x15=120)
By several players doing as player one, but following the same template
By giving each a set to different individual players.
Advantages and disadvantages
I have tried sum up what I think may be advantages and disadvantages of each option.
Disadvantage: Although one is testing only one hypothesis, but in 8 different settings, one is still not generating many designs for comparison.
Disadvantage: It takes more work
Advantage: One can get started immediately and others can tag along.
Disadvantage: It takes more work for the individual player to generate 8 set of puzzles - even if over 8 design starter templates, than just generating a ton of mutations in single experiment set based on 1 starter template and one fixed variable.
Advantage: If one player misunderstands the task, the other players can still make good use of the data they generated as one whole set won’t be missing.
Advantage of option two for now. We can get started generating experiments now and have others follow when they are ready.
Disadvantage: Can only be run properly with many players working together.
Future advantage: If there are many players participating in the experimentation, this will be the best option. As one can have several players run the same set then we should not be as prone to missing out on a full set.
I have been thinking further about making an experimental plan. I want to set it up in the simplest way possible.
The plan is to end up with something that will make it easy for you to copy my experiment template or adjust it to what you need, so you can afterwards stick your experimental data into Omei's data analysis template and see if your hypothesis is confirmed or not.
- I do 4 different experiments in each lab. (Two will be fine too) These experiments I will repeat across all labs.
- The experiments will be fitted to if it is an Exclusion lab or a Same State lab. I will use design setup that had shown themselves to work there.
- Each experiment will have two puzzles series with close to identical designs. One puzzle series without the specific feature you wish to test and the other with. In my case a GU in the switching area. 4 puzzle series with GU and 4 puzzle series without. So this make 8 series of puzzles in each lab.
- I will as far as possible attempt to make the design with GU and the design without GU identical. (May have to change a base in a less important spot if the design I intended is already taken, or in some cases if I can't make a stable version of either the one with GU or the one without)
- I will distribute 120 slots to each lab for these experiments. That will give me 15 designs in each experiment category. And I will still have 30 slots left to do funny but suspected useful mirror, double and triple aptamer experiments with. :)
The test outcome
The main variable in my entire experiment is GU. If the fold change between the set without the GU and the set with GU in the switching area differs considerably, then the variable I'm testing is having an effect. Since it is the only thing that is really different.
My hypothesis is that GU are helpful in the switching area. But if I instead put it as a question, it is simpler to see the outcome.
Question: Are GU in switching area helpful or harmful to the switching ability of an RNA switch?
In reality I can end with 2 or really 3 different answers to the question in my hypothesis.
- Yes, GU is really helping in the switching area
- No, GU in the switching area makes everything worse
- Nah, there really is no fold change difference between designs with GU in the switching area or not. Try a new hypothesis. :)
How to analyse the data when it comes back
Here is how I plan to use Omei's analysis template to compare my results.
Omei's Data Template
- I will pool all the a-series together afterwards to compare all the b-series designs. This part of the work will be easiest doing in a spreadsheet. This I will do for each lab. That way I get to compare 60 designs with GU to compare with 60 designs without GU. Those two sets of 60 designs will be near identical except for the GU content.
- Then I will likely pool all the Same state designs in two sets and all the Exclusion designs in two sets and see if there are different trends for these two lab types. It may be that GU in the switching area is helping Exclusion designs more than in Same state designs, etc.
My Experiment Plan
There will be an identical b-experiment for each a-experiment, just without GU in the switching area.
1a) One static stem, MS2 before second aptamer
2a) One static stem, first aptamer sequence before MS2
3a) Two static stems, MS2 before second aptamer
4a) Two static stem, first aptamer sequence before MS2
5a) One static stem at late position, ms2 distanced to aptamer
6a) One static stem at early position, ms2 distanced to aptamer
7a) Two static stems, MS2 distanced to aptamer, static stems near MS2
8a) Two static stems, MS2 distanced to aptamer, static stems near aptamer gate
I only make one experiment template but I will repeat it across all the labs. So when you have first decided what to test and how, everything will be far easier from there.
You could use the same basic switch element position as in my puzzles, but test a different thing than GU. Or choose a different puzzle setup but still test for GU. Its fully up to what you can imagine, you wish to test. Also there are plenty of ideas here.
There is also talks of mutation scripts. Coding is difficult enough without doing too much in one script.
Any scripts that:
1) only do "bulkload".
2.)only look for valid mutations from a given valid sequence
I am really only interested in #2 at this time since I have submitted enough labs to get an idea of where I want to go. What's the best existing script that comes closest to #2 for any lab so I can modify it?
In the "New Progression" there is a tool called Eterna Bot which works to generate a score based on what is thought to be a favorable lab design. I recall that the increase in Eterna Bot score corresponded well with what has worked well in the recent labs and so I was curious as to why Eterna Bot isn't available as a tool/feature in any of the Lab rounds I have seen.
One thought was that Eterna Bot couldn't handle switches as a whole, but each switch has a single-state component and I would think that Eterna Bot could handle those.
If Eterna Bot doesn't have any issue scoring switches, then I would like to see this made into an available tool, similar to Melting Curves and Pairing Probability Plots as yet another aid to improve lab designs.
Making great switches switchier
What switches want
1) Most of all symmetry
2) Double aptamers (Ok, probably not all labs want them - but the riboswitch designs with best fold changes have them.)
Getting some more symmetry into Exclusion labs
I have been thinking about how to get some more symmetry stuck into our past not so symmetric solves of Exclusion lab puzzles.
Till now our Exclusion labs have been less symmetrical than our same state labs. Due to the MS2 liking to be directly next to the aptamer, it does a skewed pull. Not like the more straight pull between MS2 and aptamer in the Same state designs.
I think I have found a way around this.
I did a solve where I doubled what have worked in a past Exclusion NG 2 winner.
Ignore the #alternativems2 bit, both MS2's are true MS2's.
Blueprint addition by rotation
I like to talk about a riboswitch blueprint - which is really just a template of how the switch elements prefer to be placed in relation to each other.
There is one for Same state labs (ms2 distanced to aptamer) and one for Exclusion labs. (ms2 next to aptamer)
A thing that has worked earlier for me is to add up blueprints. Like take two different working versions of a design and add the structure of them together to get to a new structure with a shot of working. This time I rotated the blueprint 180 degrees instead.
I have made a new Exclusion series called Ultimate symmetry which has:
1) Lots of symmetry
2) Double aptamers
3) Double MS2 (will often be alternative MS2's.)
What may we learn?
Not all designs will benefit equally from having double aptamer or double MS2. I think it will all depend on the balance of strength between aptamer and switch hairpin. (MS2, K4 - kissing loop hairpin etc.)
Basically varying the number of aptamers in relation to MS2's in labs with different aptamers are a way to probe the strength of the aptamer versus MS2. I suspect that some of our new aptamers will take more work opening compared to the FMN we have worked with so long. These may benefit from having one aptamer against 2 MS2's. (At least in Same State labs)
In our past FMN/MS2 labs, two FMN countering MS2 worked real sweet. Two FMN versus one MS2 are in are in balance in the Same State NG2 lab.
What I wish for next round. Even bigger switch bubbles. :)
Basically a switch bubble big enough to stick 4 ms2's into and leave room for a small loop sequence between them. I would like to see if I could make an exclusion design work that way with 4 MS2's against one aptamer. I suspect the MS2's may help the aptamer do its job, because they may also be able to switch each other off.
The lack of a big enough switch bubble didn't stop me from trying though.
I went fibonacchi on the MS2 ON control freestyle puzzle. :)
Which really stems back to a beautiful idea that Zama brought up. She asked me if RNA could be fibonacchi like.
Since I had already planned to try stick in 4 MS2's in somewhere and static RNA literally hates too much symmetry and too similar elements, I decided to instead of spreading the MS2's in an even way, to spread them in a growing or decreasing order. Aka fibonacchi like.
So Fibonacchi helps add in asymmetry, yet in a systematic way. Alternative MS2 add in sequence variance in the otherwise identical elements elements.
Hereby Zama's idea is passed on. Go get creative. :)
Is there a way to find designs that almost have qualities (such as those Eli has highlighted) and bring them to attention to eterna’s top designers for targeted alteration?
Creating (puzzle) games within a (active lab) game?
Combining design insights with our group’s designing
The easiest way I have found to find bias is just to observe my own tendencies and then ask if these are in concert with the project's objectives. If they are not, then that tendency (which is also highly likely to be held by others) is a bias to drop.
Here is an example. Quantum Moves has 23 game levels - each simulating some aspect of quantum physics quandaries of quickly and stably moving atoms. I noticed that I had a desire to get a top score in at least one of these levels. So I had a tendency to focus on one game or a certain group of games where I thought I had a better chance of getting a top score.
Since each level incorporated different aspects of quantum physics aspects, not learning about the aspects of other game levels was not in concert with the project's goal. Therefore the tendency to want to win at one level was a bias against cross level learning.
To remove this bias, I simply shifted my goal of wanting to get a highest score in a game to improving my worst score of all games. This put my efforts more in alignment with the project's goals (of improvement) and also gave me two advantages that other players did not have.
The first advantage was better cross level learning. By always focusing on my worse game, I improved the simulated quantum physics aspect that I was worst at. And then could apply that to other games.
The second and probably more powerful advantage was to create better motivation for sustained engagement. It was both easier to play this way, less frustrating and more fun. So I played much more than other players.
As a result of dropping this one bias, and after a year of playing in spite of the fact that I had never played any computer games before, I now have the top scores in Quantum Moves in 18 of the 23 levels, including all levels from 9 and up and being in the top 5 in the other five lower levels.
In eterna, the bias I have noticed within myself is to want to do the games myself without help to prove that I can. In the lab, this has translated to a feeling wanting to create my own designs.
I assume others feel the same way.
This prevents cross person design collaboration during the most important time (labs).
How do we drop that?
Mutation Tool - improving player-oriented efficiency
I have been using Nupack less in Lab because the engine is both slower to run and process submissions. Awareness of that bias has me looking for what unique Nupack engine values I may be overlooking.
Both @Zama and I have noticed that when running the mutation tool on TEP designs (which we favor Vienna 2) our hit rates for multiple engine designs was low. When looking for what wasn’t working I noticed that it was often a stem within Target mode, State 2 of Nupack.
So instead of just fixing the aptamer and running my TEP designs thru Mutation, I also fixed combination of nt’s are were more successful for this stem within Nupack first. And then my multiple engine hit rate increases significantly....which hopefully improves Lab submissions!?
Other potential ways of improving Mutation tool
efficiency is selecting designs within design similarity proximity of
attractive characteristics. Such as
symmetry (@Eli Fisker), minimal cross-engine nt movement (@Zanna) and/or fixing
attractive design elements such as FMN aptamer orientation.
I have too many ongoing commitments to take an active role in a project like that right now, but I could certainly help guide you to the relevant data/resources if you (or anyone else) wanted to pursue that.
Back in the early Riboswitch labs I made an observation that a static stem would turn up in a huge amount of the winners. I started to speculate about that the static stem was necessary. That it had a function on its own.
For background see the section No Static Stem.
Particularly in the Exclusion NG 2 lab did this stand out. In our lastest riboswitch lab (101), roughly 95% of all the winners have the static stem right next to the aptamer gate.
I ended up doing some experiments, where the space for the static stem got deleted. All designs I did this to across labs, ended up with a lower score than the original designs except in one case.
Here are the two small loop labs that are equivalent to the Exclusion NG 2 lab. All these designs are based on winning Exclusion NG 2 designs, but without space for and the sequence of the static stem. They all took a score hit.
Omei's insight + mine = Is the Static Stem in the switching area doing Coaxial stacking?
What I'm really interested in now is getting something specific tested.
Omei has earlier brougth up that stems when being next to a sequence that would bind up with an outside input, were doing coaxial stacking and helping the input bind with the sequence next to the
Intro to flush stacking energy
I have started to wonder if not the static stem in the switching area of a riboswitch, when next to the aptamer or MS2 is doing coaxial stacking.
Combining these two ideas
1) Static stems are (often) necessary in the switching area
2) A coaxial stacking aids the binding of the sequence next to it
And it would pretty much make sense that static stems do have a function.
Static stems seem necessary at specific spots and those specific spots are somewhere where coaxial stacking will help the fold.
Potentially allowing for a coaxial stacking of the static stem with the aptamer gate and as such potentially aiding the bind of the FMN molecule.
The Nature of Static Stems
I basically think static stems are a bit like mushrooms. If there are enough bare soil, more will pop up. So if there are excess bases not in use or needed for the switching area itself, a static stem will come in handy.
If there aren't excess bases, a static stem isn't needed. If there are lots of excess bases, more static stems are needed.
I also think that if there is space for two shorter static stems, that they will be better than one real long static. Basically RNA seems to not be too happy about all too long stems. Unless some GU or mismatches are stuck into them. Also if coaxial stacking is occouring, then two static stems would mean two energy bonuses. :)
Additional experiment proposals
While I have gotten closer to have my experimental starter designs put up, I realized that in some labs, the aptamer took so much place or the switch elements were placed in such a way, that I can only run 1 out of 4 experiments. Thus I have 90 slots to spend for other experiments.
What I'm thinking of is to use them on a design with 1 static stem. And do something like change the position of the static stem, so it in 30 designs will be next to the aptamer gate, in 30 be next to the MS2 and in the last 30 be inbetween.
It could also be interesting having frequency experiments where the static stem gradually gets moved between being next to the aptamer gate to being next to the MS2. In a systematic manner. Like the ones Omei has done and I show in this intro to using eterna spreadsheets.
In particular in the CRISPR/FMN NG labs, this should be interesting to test as we can literally stick in past winners. And then move around the static stem.
Get creative... :)
Ultimate Symmetry Continued
My Ultimate Symmetry series in Exclusion labs holds double aptamers.
I put in rotated aptamers with the intention of getting the aptamers turning their favorite orientation towards the switching area.
However I have realised there may be a tiny problem... :)
Namely that if the aptamers are placed like this and the rest of the puzzle scaffold are not strong enough to hold the aptamers, the following may happen.
The aptamers may stay ON in both states.
The aptamers may instead of shutting off, find each other's matching FMN half, do an aptamer rescue mission, so both the aptamers will stay turned ON.
I have earlier called the kind of aptamers for mirror aptamers. But really the extra aptamer I added is rotated 180 degrees in relation to the locked aptamer.
So I have started to suspect that we will have a better shot off getting the Ultimate Symmetry designs to work, if we instead make Same turning aptamers.
One more Experiment
I think this call for another experiment pitting two such sets against each other. :)
#sameturningaptamer versus #rotatedaptamerSameturning Ultimate Symmetry versus Ultimate Symmetry
Biased Guide DNA
I wonder if the guide DNA chosen for the CRISPR labs have to do with anything specific? I wasn’t able to look up the sequence. Tried it backwards too. ;)
I couldn’t help notice that the guide DNA for the CRISPR labs have a strong sequence bias. The target DNA has CU (pyrimidine) bias, whereas the RNA part of it has GA (purine) bias.
I happen to like it. It is very switch like. I won’t be surprised if there is some bias to where CRISPR likes to land.
Why do switch RNA like repeat sequence?
Back when switches were new in lab, they caused me wonder as to why they would carry so much repeat sequence. Turned out the repeat bases in the design came from the locked bases in the FMN sequence. The aptamer itself carried repeat bases and as such sparked repeats.
However I found out this was not an isolated incident just relevant to the FMN aptamer.
The sequence repeat seems central to switch elements like aptamers, MS2’s, microRNA’s and switch inputs in general.
Long and short RNA bases
I think there is a specific reason for this. I think it helps them switch... :) Bear with me.
There are long bases and there are short bases. The short bases are Cytosine and Uracil. The long bases are Guanine and Adenine.
Why do basepairs pair up?
RNA behaviour explained with Lego
I have found a new and better way to illustrate my point that RNA switches are having certain repeat bases and why.
Static RNA likes its base pairs rather well mixed up. Switch RNA is different.
Switch RNA tends to hold rather specific repeat sequences.
At least when it comes to lego, it is obvious why the mixed bases at the left bind much better together.
Whereas there are little except hydrogen bonds to hold the two RNA stacks at the right, together. I guess the bases can stack better when they are of similar size. So for the switch bases, they can bind through hydrogen bonding, but them not truly mixing,
Haven’t had enough Lego? Read Ksteppe's beautiful introduction to energy in the RNA world.
For the background story on repeat sequence in switch elements see:
Adventure in Riboswitch Wonderland
Here is the backstory of finding the periodic repeats in the early EteRNA Switch labs:
Can periodic repeats in RNA switches be programmed?
Hi Eli -
If you have time, take a look at these two designs. Zama sent me the first. I liked it because it had minimal movement.
So I added another static stem closely on the other side of the aptamer. So the aptamer is closely bordered by two static stems.
Also the folds & movement in all three engines are relatively the same.
I am trying to employ what I understand from your observations to improve designs I come across.
Is the altered design an improvement?
Yes, you did improve the design by tying some of all the excess bases away. However your design and Zama's are likely not going to have the MS2 turned off.
In this case minimal movement is likely not going to be good. (But keep looking for it other places)
This is an exclusion design. What they usually need (Talking of FMN that I know) is the following
1) MS2 next to one of the aptamer sequences. Check - you got that!
MS2 is strong, so just the opening base pair splitting will not be enough to turn it off. The MS2 molecule binds at the hairpin loop. So it needs a helper sequence to get shut off.
2) A turnoff sequence that is right after MS2 and preferably targets an identical sequence stretch that is present in both MS2 and in the aptamer. This one both of you are missing.
Best way to show this is to check this past winner: http://www.eternagame.org/game/browse/6369184/?filter1=Id&filter1_arg2=6456051&filter1_arg1=6456051
Swap between the states to get a feel for it. In particular notice the base stretch at 44-48. This is the turnoff sequence.
Also take a look at this puzzle again: http://www.eternagame.org/web/puzzle/8057283/
And I have a question about OpenTB ... What our gamers give to medicine ? Is any company started to make a drugs that can heal tuberculosis or it is just for make gamers to believe that they do an important work and it doesn`t give any result ?
As for increasing players' quota of slots, it's definitely on the table for consideration. But there was a rationale for setting it where it is. Even at 150 slots per puzzle per player, it would be possible for about 20 proficient players to fill up all the experimental slots. A few, like you, have the dedication and patience to generate that many designs without any script assistance. But there are even more who could simply use their familiarity with scripting to generate however many designs they wanted.
Basically, we wanted to try to level the playing field between the few technically proficient and the rest of the players. It is a two-pronged approach. First of all, to give all players some access to automated tools, but at the same time try to diversify the submissions by encouraging as many different minds as possible to tackle the problem from their unique perspective. Hence the per/player quotas were set relatively low.
We've never been very good at predicting in advance how many players and how much effort will go into a specific lab round, and so there is always some guessing at the beginning. Some times quotas get lowered as time goes on, and sometimes they get raised. Sometimes deadlines are extended and sometimes unused synthesis slots are transferred to a different experiment. In all probability, one or more of those will happen in this round as we get closer to the deadline.
So thank you for your input, and most of all, your dedication!
Eterna was (and is) at the frontier of this challenge. The OpenTB challenge demonstrated to the research community that it is feasible to design a single RNA molecule that can sense and "compute" the relative ratio of three blood-born messenger RNA molecules that is highly correlated with the human body's response to active TB. That is only the first of several innovations that will be needed to make the dream a reality. But it has made the point strongly enough to prompt the next stage in the development process. I don't want to preempt the Eternacon excitement by saying more here, but do stay tuned, digitally if you can't make it to Eternacon in person.