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1 Tutorial Optimal Learning in the Laboratory Sciences The power of interactivity December 10 2014 Warren B Powell Kris Reyes Si Chen Princeton University http wwwcastlelab ID: 314320

information probe region highest probe information highest region experiment interactivity scores bind prior temperature rna accessibility gradient signal knowledge

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Slide1

Slide 1

Tutorial:

Optimal Learning in the Laboratory SciencesThe power of interactivityDecember 10, 2014

Warren B. PowellKris ReyesSi ChenPrinceton Universityhttp://www.castlelab.princeton.edu

Slide

1Slide2

Lecture Outline 2The power of interactivitySlide3

InteractivityGuiding the experimental process requires balancing a number of objectivesWe would like to run experiments with the highest chance of success.We also want to learn the most to guide future experiments.But we also have to consider the cost and complexity of an experiment. 3Slide4

InteractivityPrior estimate

Value of informationTemperature

PressureHighest value of informationTemperature

PressureThe experiment that produces the highest value of information might require using the highest temperatures and pressures.The scientist has to balance the performance of an experiment, the value of information, and the complexity of the experiment.Slide5

InteractivityThe accessibility of a region of an RNA molecule mediates interaction with other molecules.Depends on how you define interactions, resulting in several methods for accessing accessibility.MechanisticEnergetic

Mechanistically accessible region

Well-protected region = inaccessible

Designing

probles

for an RNA moleculeSlide6

Designing

probles

for an RNA moleculeNew Methodology: attempt to bind probe/reporter complex with fluorescent marker. If bound, we observer strong fluorescence signal. Interactivity

Probe/Reporter complex

If probe can bind, we get fluorescence signal, indicating accessibility.

If a probe cannot bind, then we get no fluorescence signal, indicating inaccessibility.Slide7

Knowledge Gradient scoresHigh confidence in prior DMS dataEach bar is a potential region to probe. The vertical axis is the KG score.Slide8

Knowledge Gradient scoresLow confidence in prior DMS dataThis plot tells us how much information can be gained from targeting each region.Highest scoring regions = most information to be gainedSlide9

Knowledge Gradient scoresUse KG scores as a guideline to picking the next experiment.The primer for this highest scoring probe need to be ordered

But we have this primer in stock, and it has a reasonably large KG value.Slide10

DMUSHex

NB La

20 30 40 5040302010Temperature (C)ConcentrationPhase DiagramSlide11

Policy function approximationsLookup table policies arise in many settings in everyday life© 2013 W.B. PowellSlide 11