EteRNA: Let's work on a paper together

General Science Discussion
1

One of the most important things we’ll be trying over the next year is to have EteRNA players start writing their own papers – share your hypotheses and experimentally validated knowledge with the entire scientific community!

We (the devs) will of course help with the first submitted papers, but eventually our hope is that we won’t be directly involved (and won’t even be authors). That means we need to teach you how to formalize your knowledge.

As a sort of pilot experiment, we are wondering if we could get your help in reviewing the RNA literature. JP Bida, a postdoctoral fellow in my lab, and I are writing a review on recent approaches and problems in RNA design. (Note that Jp is working with me on the new ‘cloud’ for EteRNA experiments as well.)

One remaining task is to ‘score’ the reviewed papers – a few need to be marked as ‘recommended’ and as ‘highly recommended’. We were wondering what you – the EteRNA citizen science community – think about these papers, and whether you would recommend additional publications. Indeed, we’re very curious to see if you have similar rankings to us.

Jp has prepared a reference list with approximate categories, compiled links to the PDFs, and a Google spreadsheet to record your numerical rankings (1 to 5, where 5 is most recommended) and comments. He’s putting them in the next post below.

We’d welcome your thoughts on as many or as few of the papers that you can look through. This is totally experimental and voluntary – but could be the beginning of something transformative in publishing!

As a second stage, we’re thinking of also posting Jp’s draft in a week or so, and getting your comments about the text itself – are any of you interested in help with this?

Feel free to add additional comments or suggestions below.

2

Hi EteRNA community,

As Rhiju mentioned above we are writing a review on RNA design. We have collected a large number of publications recently written on the topic and need help selecting the best ones by 2/24/2012. Please visit the links below to vote on the best papers and identify public copies of the manuscripts.

Instructions
https://docs.google.com/document/d/1r…

Paper List
https://docs.google.com/spreadsheet/c…

3

Very cool idea. Are there any specific criteria you would like us to use when rating the papers?

Also… a couple of fixes for links that led to the wrong place.

Characterization of anti-NF-kappaB RNA aptamer-binding specificity in vitro and in the yeast three-hybrid system.

Organization of Intracellular Reactions with Rationally Designed RNA Assemblies

And a couple of papers:

Aptamer-Based Viability Impedimetric Sensor for Viruses

The shape-shifting quasispecies of RNA: one sequence, many functional folds.

The links should all be open-access.

4

ok well I might give this a go - it sounds interesting but ‘clarity’ of language/diagram is probably going to be the criteria by which I judge any paper (as they are all likely to be too technical unless you have a degree in this sort of stuff).

5

That’s a good point. On one hand, RNA structure/design touches on a lot of areas of math & science. On the other hand, a surprisingly large number of these concepts can be made intuitive in games – for example the most sophisticated scoring function available for RNA secondary structure is in EteRNA.

Perhaps, if you have time, you can help us get a list of concepts that you encounter in the literature that are confusing – and then we can see about how they might be made intuitive in future versions of the game, or via simple tutorials or wiki pages. We are also thinking of making a few video tutorials that explain the ‘Chemistry behind EteRNA’ and the ‘Physics behind EteRNA’, but need a sense of what concepts are most in need of explanation.

6

Hi Rhiju, Quasispecies, Ed and other followers of this post!

Quasispecies posted a question in the FAQ on how to get a common language, that appears to be related to this discussion, so I will just throw in a link, to share my thoughts on shared language as a step on the road to read and rate science papers.

Also I have a small collection of educational resources where I share how I take a go at science papers and the like. I post the link in the hope that it can serve as inspiration on the way to read, understand and later publish science papers.

7

Hi!

When I voted on an article (Aptamer-based regionally protedted PCR…) that was voted on already and copied my name in, the previous votees name dissappeared. Just wanted to check that I didn’t delete anything.

8

Funny and unserious intro on how to read science papers:

A Key to Scientific Research Literature

Enjoy!

9

Here is another interesting peek into the world of science papers. This blog post by Derek Lowe is about Commenting On Scientific Papers: How Come No One Does It?

10

The review paper that we worked on has just been published here:

Bida, J.P. and Das, R. (2012) “Squaring Theory with Practice in RNA Design”
Current Opinion in Structural Biology, in press.!

If you don’t have access, the PDF is here.

Thanks to everyone who helped go through papers & made comments on the manuscript.

Note that EteRNA players are acknowledged in the review, and check out Figure 4!

11

Here is what the paper is about:

The paper is about building nanosquares with RNA structure designing algorithms.

The wish is to find enough of the basic rules for RNA folding, to gather them into a structure prediction algorithm, let it loose on a yet unsolved problem and get success with solving it. This can’t be done with the algorithms available today. The example with building of nanosquares, illustrates how far scientists have got with solving this concrete problem.

But using new technologies and new approaches, shows great promises for the future. The systematic play with small RNA designs in lab, like we Eterna players are doing, helps uncover some of the unknown and missing rules. This and other new approaches is giving hope for making better RNA designing algorithms that will get us closer to success with RNA structure designing from scratch.

This will help provide better tools for solving medical problems. The problem remaining is how to analyze the massive amount of data, due to new and faster technologies and how to get what we learn together, scientists with citizen scientists, put into more effective RNA designing algorithms.

Notice the wordplay in the title on nanosquare. :slight_smile:

12

Rhiju asked me to read through his and JP Bida’s paper. I asked for explanations for some of the hard words. Bida gave me some really nice definitions.

My absolute favorite is his explanation on Heuristics:

HEURISTIC - Rules for solving a problem based on experience and not necessarily physics. For example, if you want to hit a castle with a catapult you could use the heuristic rules.

  1. Fire the catapult
  2. If you fired too far raise the pin
  3. If you fired too short lower the pin

Or first principles

TOPOLOGY - The topology of an object is a description of its shape that ignores its specific geometric form. Objects have the same topology if you can make one shape from the other shape without having to cut it. For example, a circle has the same topology as a triangle, square, or any other polygon.

OPTICAL MELTS - DNA and RNA absorb certain frequencies of light if they are single stranded v. double stranded. Optical melt experiments shine a light on a sample of RNA or DNA and measure the amount of light that passes through the sample. As the sample is heated and the RNA or DNA become single stranded they amount of light that passes through changes. By measuring the temperature and the change in light you can determine the energy stored in RNA or DNA duplex with different sequences.

BI-STABILITY - RNA molecule that has an equal chance of being in two different folds. For example, if you have ten RNA molecules in solution, five would be in fold1 and five would be in fold2.

RING-LIKE - In this case we are referring to multiple RNAs connecting to each other and forming a ring shape.

ALLOSTERICALLY COUPLED - If two domains are allosterically coupled it means information about a ligand binding to one domain is transmitted to the other domain through a change in the fold of the RNA, like the RNA switch puzzles.

SIGNAL RECOGNITION PARTICLE RNA - this is just the name of a particular RNA sequence that was redesigned with Rosetta.

Signal recognition particle RNA

INTER-STRAND DOCKING - This is when two different RNAs physically connect to one another usually by forming a helix between two strands. This differs from intra-strand docking referring to a single RNA folding onto itself.

I’m sure there are more words we don’t understand. Please bring them up in this forum post and let us work out what they mean. Some of you players have real life biology and chemistry background. Feel welcome helping us understand.