2015.10.30 Community Chat

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On How to Make Lab Mod Submissions Walkthrough, & Tips for Solving TB-A/B MS2 Labs




[14:49] Jennifer Pearl hi

[14:55] machinelves hi Jen

[14:56] Jennifer Pearl hi Elves

[14:56] Jennifer Pearl !!!

[14:56] machinelves hellooooooo!!!

[14:56] Jennifer Pearl how are you?

[14:56] LFP6 Hey all

[14:56] Jennifer Pearl I just applied to a couple new jobs

[14:56] machinelves hi LFP6!!

[14:56] Jennifer Pearl but now for RNA fun

[14:56] machinelves congrats Jen, that is awesome!

[14:56] machinelves hehehe

[14:56] Jennifer Pearl Hi LFP6!

[14:57] Georgia- hey guys

[14:57] Jennifer Pearl hi Georgia

[14:57] machinelves Hi Georgia, welcome!

[14:57] machinelves If anyone has prepared a walkthrough for labs just let me know, and otherwise we'll be learning how to do mods today

[14:58] Jennifer Pearl cool

[14:58] whbob Hi

[14:58] machinelves hi whbob! welcome back

[14:59] Jennifer Pearl I do have a quick question for LFP6

[15:00] Jennifer Pearl @LFP6 how comes the cluster size in the sript output?

[15:00] Jennifer Pearl script

[15:00] LFP6 haven't heared more from John

[15:01] whbob @ Elves:Thanks.  I could try a short walkthrough of the labs, but I may need help with links. 

[15:01] LFP6 All I know is that he's working on a new API I'll be able to use

[15:01] Jennifer Pearl ok. cool

[15:02] machinelves whbob, perfect! I have links prepared, so in that case i'll walk us through the simple part of getting labs open, and up to the point of mods, and then hand off to you for making more complex and original designs

[15:03] whbob OK

[15:04] machinelves ok friends and gentlefolders, first things first, open up a text editor for copy / paste fun and games.

[15:04] machinelves this way you can save the info you want for pasting into your lab description later

[15:05] machinelves Now let's go check out the active labs using the top menu http://prntscr.com/8x82uh

[15:05] machinelves that will bring you to this page: http://www.eternagame.org/web/labs/

[15:05] machinelves In a previous community chat, we looked at how to read the description. Let's scroll down to click Participate, and see how to make our own mods. 

[15:05] machinelves http://prntscr.com/8x839i

[15:06] machinelves That will take you to this current active lab, and in future lab rounds this page will be different: http://www.eternagame.org/web/lab/6204762/

[15:06] machinelves When you scroll down you will see multiple challenges. Today let's do the first design challenge. Right click on the Vote button to open player submitted designs in a new tab 

[15:06] machinelves http://prntscr.com/8x8416

[15:06] machinelves Now let's go back to the first tab and click on the first challenge's Design button to launch the sequence designer for creating your submission.

[15:07] machinelves http://prntscr.com/8x84bv

[15:07] machinelves You should now have three windows open - your text editor, the list of player designs, and the window for designing your own submission.

[15:08] machinelves Later on when whbob shows us how to make unique designs, you can skip the step of opening other player designs. For now, we need these windows so that we can find a design to copy and modify ( "mod" )

[15:08] machinelves Now let's go to the Vote for Player Designs window, where there is a full list of submitted designs to choose from. 

[15:08] machinelves http://prntscr.com/8x81se

[15:09] machinelves You can pick any design you like to mod from, for now I picked one that had a description that sounded interesting

[15:09] machinelves Notice that you can search in the columns, and type "a before b before ms2 2" into the Title search field. 

[15:09] machinelves Click on the design with ID number 6278119, the top option in search results if you do not type the full title

[15:09] machinelves http://prntscr.com/8x89as

[15:10] machinelves In your text editor write down the name of the lab and author, A before B before MS2 2 (Eli Fisker).  

[15:10] machinelves http://prntscr.com/8x7uu5

[15:10] machinelves Click on Get URL for this design and copy it into your text editor.

[15:11] machinelves http://prntscr.com/8x7uke

[15:11] machinelves Now we have preserved the key info for citing where this mod came from in your description.

[15:11] machinelves here's the link to the design for anyone who wants to catch up fast: http://www.eternagame.org/game/browse/6204761/?filter1_arg1=6278119&filter1_arg2=6278119&filter1=Id

[15:12] machinelves Also, from the player design vote page popup, you can click View/Copy to see what this design looks like

[15:12] machinelves http://prntscr.com/8x7vfr

[15:12] machinelves To copy the sequence, click on the Options button and click Copy to copy the sequence of nucleotides for this design to your clipboard.

[15:12] machinelves http://prntscr.com/8x80mu

[15:12] machinelves http://prntscr.com/8x7zwg

[15:13] Jennifer Pearl that is a good idea getting the URL too

[15:13] machinelves Now you can paste the sequence in your text editor, or just go straight to the Design tab that you have open from before, and paste it in there. 

[15:13] machinelves thanks!

[15:13] machinelves You can do this by clicking on the options button, and then click Paste

[15:13] machinelves http://prntscr.com/8x7y0x

[15:13] machinelves A window will pop up where you can click in the text field and press ctrl+v / cmd+v and paste the sequence in.

[15:13] machinelves http://prntscr.com/8x7zgo

[15:14] machinelves Now you will see the nucleotides change color to match the design that you copied in!

[15:14] machinelves You will also see all the requirements are now met and have green checkmarks. Success!!

[15:14] machinelves http://prntscr.com/8x8cxh

[15:14] machinelves Now is the fun challenge of finding which nucleotides you can mutate, while still keeping all those requirements met.

[15:14] machinelves Try selecting one color, and mutating one nucleotide at a time. 

[15:14] machinelves http://prntscr.com/8x8dsu

[15:14] machinelves You can press the letter z to undo and go backwards if it didn't work out.

[15:14] machinelves http://prntscr.com/8x8eg2

[15:15] machinelves In the previous example I changed nucleotide 83 from red guanine to yellow adenine and it didn't like it.

[15:15] machinelves But I can change nucleotide 9 from blue uracil to yellow adenine and it's just fine.

[15:15] machinelves Keeping track of the specific mods that you make will be great for the description, but don't worry if you don't track them all, since as long as you copy in the source info, the sequences can always be compared.

[15:15] machinelves Once you have made the mods you want it's time to publish your solution!

[15:15] machinelves Make up a title like "Mod of .... " and put the info you saved in your text editor into the Comment Description field.

[15:16] machinelves Making sure you cite the origin of your mod will help us analyze and chart the data with the most accuracy

[15:16] machinelves http://prntscr.com/8x8hdh

[15:16] machinelves I'm going to pause briefly for any questions and then hand off to whbob for custom design tips in this lab

[15:16] Jennifer Pearl from personal experience I did a mod I wanted to keep track of and did not record the exact name and url and now cant find the original

[15:17] Jennifer Pearl let alone someone else being able to find the original

[15:17] machinelves ah yeah, I also have found it challenging to look up past specific labs sometimes. 

[15:18] Jennifer Pearl keeping good records is very important

[15:18] machinelves I'm not entirely sure if the URL ever changes once it is filed out of active labs and into archived labs. So I figured both name and URL would be good

[15:19] machinelves especially when with thousands of submissions the titles often start to sound similar

[15:19] machinelves ah one more thing, don't be discouraged if you try to publish your design and it says it is already taken. that just means someone else already is making that sequence. back up and try again!

[15:20] machinelves this is one reason it's good to start early in labs, since the possibilities are still wide open

[15:20] machinelves Okay did anybody get stuck, or need any clarification or direct links? For this next part, we want to have our active lab design tab open

[15:21] machinelves http://www.eternagame.org/game/puzzle/6204761/

[15:21] machinelves whbob, when you're ready, we are happy to learn some tips and tricks on making our own unique designs in this lab

[15:21] whbob @ Jen: you can see your submissions on yuor profile page.

[15:23] Jennifer Pearl Thaks whbob, I only have a hard time finding the original design i based mods on

[15:24] whbob In the list (vote)page you can type your name in "designer" and see just your submissions.

[15:24] machinelves oh that's a great reminder... go to Me - My Profile from the top menu, and click on Synthesized RNAs http://prntscr.com/8x8s6w

[15:25] machinelves Tracing backwards to the mod origins is something that would be great to have automatically built into the game's record keeping, but until then I think we have to track that manually ( unless I am missing...

[15:25] machinelves ...something )

[15:26] machinelves And one of the Das Lab scientists is doing a study on the evolution and origins of designs to understand which ones came from where, so it will be a huge help to them as well

[15:26] whbob I try to make the description different for new designs and use dot 1,2,3 with the same description for mods

[15:27] Jennifer Pearl so if the original design was named "test" you would do "test.1"?

[15:27] Jennifer Pearl for a mod\

[15:28] whbob Probably "mod of test_V1" then add .1,.2 for additional designs

[15:28] machinelves here's a link to the evolutionary tree discussion in the forums https://getsatisfaction.com/eternagame/topics/lab-submission-evolutionary-tree

[15:29] machinelves that's a good naming system! 

[15:29] Jennifer Pearl @whbob so if you id d amod of your own mod then you would do .1

[15:30] whbob If you can go to the (vote) list page for the R2 labs I have a few submissions at the top of the list 

[15:30] Jennifer Pearl ok

[15:30] whbob @ jen: yes I mod my designs the same way

[15:31] Jennifer Pearl i will take a look in a moment. I have some things to take care of for a moment

[15:31] whbob np, does anyone have questions?  

[15:31] machinelves i like that this numbering system means you can search for the root name and get back all the mods at the same time

[15:32] machinelves yes please, I would love to know your general approach to solving the labs from scratch. or advice on how to make a unique design as opposed to a mod with only a few nt changes

[15:33] whbob OK, when you start by clicking the design button, you will get the design page.

[15:34] machinelves okay i am with you

[15:34] whbob If you have never submitted a design or tried to make a design, the RNA main strand will have all As.

[15:35] whbob If you have started some design, it will show where you left off.

[15:35] machinelves it's interesting to see that since I did not submit my design, it is indeed all As. This is unlike solving a puzzle which remembers your last progress even without solving...

[15:35] machinelves ohh hmm. i wonder why mine went blank!

[15:36] whbob Maybe you do have to aubmit it?

[15:36] whbob *submit

[15:36] machinelves i'm not sure. if you are concerned about saving your progress remember you can always copy your own design and save it in a text file

[15:37] whbob I do that whenever I have a design ZI like.  I don't submit it right away.

[15:37] machinelves that sounds like a good idea

[15:38] whbob In the design page, I like to have both states open side by side

[15:39] machinelves that is PiP mode? 

[15:39] whbob The target button shows just a round open loop sequence.  there is no shape.

[15:39] machinelves http://prntscr.com/8x8ymd

[15:39] Jennifer Pearl i  will be afk for a few minutes

[15:40] whbob @Elves: yes.

[15:40] machinelves thanks!

[15:40] machinelves and here's target mode http://prntscr.com/8x8za9

[15:41] whbob This is a unique lab where you can put the MS2 hairpin and other nucleaotides(nt's) anywhere you want

[15:41] whbob *nucleotides

[15:42] machinelves that is pretty cool. 

[15:42] machinelves in past labs MS2 hairpin was locked

[15:43] whbob There are constraints that must be met, but the location of the MS2 hairpin is not one of them.

[15:43] machinelves but now we get a super cool nucleotide pattern stamp for it

[15:43] whbob There is a constraint that the MS2 haqirpin MUST form in state 2, but not in state 1.

[15:43] machinelves http://prntscr.com/8x90jy

[15:45] whbob I wrote down the nt's of the two oligo's, TB-A and TB_B, AND the MS2 sequence.

[15:47] whbob On paper I can see how these sequences can have complementary nt's and that is important for any design.

[15:47] Jennifer Pearl im back sorta

[15:48] machinelves wb Jen

[15:49] Jennifer Pearl thanks dealing with work stuff

[15:49] machinelves here we can see the two MS2 constraints up top, both require the MS2 sequence, but in one state the hairpin forms while in the other state it does not.

[15:49] machinelves http://prntscr.com/8x92dr

[15:49] whbob The first part of the MS2 strand has complimentary nt's with TB-B

[15:51] whbob TB-B is a longer strand than TB-A and TB-B has more C's so it seems to be stronger than TB-A

[15:52] whbob Some designs have TB-A in one state and TB-B replacing TB-A in the other state.

[15:53] machinelves is this important because when part of MS2 has complementary nts with TB-B, those two parts can bind together, preventing MS2 hairpin from forming?

[15:54] whbob Yes, some designs pull the <S2 hairpin apart

[15:54] whbob *MS2

[15:54] whbob TB-B can do that

[15:55] machinelves why are some parts of the molecule not glowing with yellow borders? http://prntscr.com/8x95df

[15:55] machinelves do those correspond to the TB-A / TB-B strands?

[15:56] whbob Yes.  Mouse over those strands

[15:56] whbob You will see their tag names

[15:57] machinelves and so each separate piece is a separate small piece of RNA

[15:57] machinelves omg!!

[15:57] machinelves thank you that is awesome

[15:57] whbob Yes, the oligo's are micro RNA's

[15:58] machinelves so the part that is not glowing yellow in that state, is the oligo that is NOT supposed to bind

[15:58] whbob In this case, they are miRNA's that actually occur in TB

[15:58] machinelves or biomarkers that occur when TB is present

[15:59] machinelves so for state 1, the constraint says do not bind to TB-A, and the piece that is not glowing is TB-A, and it's just there to show us whether or not the rest of the design binds to it?

[15:59] whbob The yellow outlines usually mean that the part that is "glowing" has not made it's constraint

[16:01] machinelves ohhh thank you

[16:01] machinelves http://prntscr.com/8x97qi

[16:01] whbob When you switch to the natural mode, the sequence will take form and show you which miRNA has bonded with the main sequence

[16:02] whbob Gosh, time fly's, does any one have questions?

[16:02] machinelves http://prntscr.com/8x98cm

[16:03] machinelves wow indeed!

[16:03] machinelves i am really happy we made some progress in understanding the parts involved. 

[16:03] machinelves i am still curious how you get started designing from scratch - do you just start placing random nucleotides everywhere?

[16:04] machinelves do you try to pair up the TB-A or TB-B to the main body of the design by giving it complementary binding spots?

[16:05] whbob I place the MS2 hairpin somewhere in the state 2 strand because it is supposed to form there

[16:06] machinelves ahhh good tip, thanks! and then work backwards to prevent it from folding in state 1?

[16:06] machinelves ( viewing in natural mode? )

[16:06] whbob Yes, exactly!

[16:06] machinelves ahhhhhaaa!!!! awesome. giant lightbulb just went on, wow

[16:07] machinelves thank you very much that is exactly the kind of tip i was hoping for

[16:07] machinelves and it makes more sense too now that we got to go over the moving parts

[16:07] machinelves thank you very much whbob!!

[16:07] whbob Looking at the designs in teh (vote) list will help you get ideas

[16:08] machinelves i noticed we can access that directly from the design interface now in the options menu ( thanks Nando? ...)

[16:08] whbob Your welcome.

[16:09] machinelves http://prntscr.com/8x9b0f

[16:09] whbob In the design page yuo can use the "U" and "D" keys to go through the design list.

[16:10] machinelves ohh yes thank you. instant next and previous woohoo!!

[16:10] whbob There can be some delays before the page updates 

[16:11] whbob There are examples of amazing designs there

[16:11] machinelves I really enjoyed reading the descriptions as well

[16:12] whbob I thought desc. were just as long as the submit box.  Later I noticed thet you could put many lines there

[16:13] whbob I was doing "microtweets"

[16:14] machinelves oh! haha that's funny. succinct is good too. But yes, that's the gold mine of related info for each submission

[16:15] whbob There seems to be two strategy's.  Slide the MS@ or bust it wide open

[16:15] whbob *MS2

[16:16] machinelves ahh that's a good tip as well. so to prevent MS2 hairpin from forming you can either convince it to scoot over / slide down one side. Or break it open entirely

[16:17] whbob Yes

[16:18] machinelves i wonder if there is a difference in which approach is more reliable to prevent MS2 from binding. since with sliding technique, I assume some portion of the hairpin is still formed or accessible?

[16:18] machinelves but also seems less chaotic for sliding back and forth as a switch

[16:20] whbob Eli has written about this.  He has seen wherebusting MS@ open has scored well.  It may depend upon where the MS2 hairpin is placed in the main sequence

[16:21] whbob Nando has a wonderful explanation of sliding the MS2 hairpin on his blog but I've lost the link

[16:22] whbob Eli ans Omei have discussed similar tactics in the forums

[16:22] whbob 8and

[16:22] machinelves Nando's blog is full of awesome stuff. not sure which one... http://eternawiki.org/wiki/index.php5/User:ElNando888/Blog

[16:23] whbob I don't see it there, but if I can find it later I'll pm you the link

[16:24] machinelves I recall Eli had a thread in the forums making observations about MS2, i'm not sure if this is it, I thought maybe there was another as well https://getsatisfaction.com/eternagame/topics/johan-s-microrna-lab

[16:26] whbob @Elves: yes that's it

[16:26] machinelves woohoo!

[16:27] whbob This latest lab has brought back the MS2 so we will be able to see more data as to which strategy is better.

[16:29] machinelves that is very cool