CAGEN draft

The Critical Assessment for Genetically Engineered Networks (CAGEN, pronounced "cajun") is a new competition designed to improve the robustness and performance of human-designed biological circuits and devices operating in cells. The competition is intended to bring together leading research groups in biological circuit design to compete to demonstrate their abilities at designing circuits that perform in a prescribed manner in a variety of cellular contexts. Each year, a steering committee will select one or more challenge problems that involves the design of an increasingly complex set of biological functions in a range of environments. Teams must submit their sequences, plasmid DNA implementing their circuit and data characterizing the performance of their system against a specified test suite. The top 3-5 designs will be submitted to the NSF BIOFAB for final characterization, and the winner will be selected based on a set of quantifiable metrics.

CAGEN Challenge Guidelines

1. Challenges should specify tasks that, if achieved, would imply that significant improvements in the state of the art have been made. The descriptions should as much as possible be agnostic as to the approach: circuit design, organism used, etc. should not be specified. On the other hand, it should be clear from the stated metrics that the task is not doable without a robust design.
2. Challenge descriptions will be posted on the CAGEN website along with discussion threads for at least one month. The descriptions can be be revised during this time.
3. The author/moderator can request that the challenge be approved by the CAGEN board, after which time it is posted as an official challenge.
4. Changes to the challenge description can be made yearly, after the awards (if any) for that year are made.
5. Contestants submit publishable work to CAGEN along with a description of how the work addresses the challenge. There will be a yearly due-date.
6. The CAGEN board assigns reviewers for each challenge. The reviewers use the metrics defined in the challenge description to evaluate each proposal. The following outcomes are possible:
   1. No award: none of the submissions significantly improve the state of the art.
   2. A single award: one of the submissions meets the metrics in the challenge and substantially improves the state of the art.
   3. A tie: multiple submissions offer a similar level of improvement on the state of the art.

CAGEN Challenge Proposals: 2011-12

The following challenges have been proposed as possible CAGEN challenges for 2011-12.

Robust synthetic developmental patterning

Synopsis: The goal of this challenge is to design a circuit that can express a fluorescent protein with specific self‐generated spatial patterns. These patterns should ideally emerge without external spatial cues. The two basic patterns we consider are: (1) A circular pattern with a diameter of exactly N cells, where cell are on at the center of the circle and off outside (2) A striped on‐off pattern with a wavelength of exactly N cell diameters. The boundaries formed should exhibit a sharp turn‐on and turn‐off functions on the order of one cell length with minimal errors (no off cells in the on area and vice versa).

Synthetic developmental patterning challenge. The ideal circular (left) and striped (right) patterns for this challenge. Boundaries for challenge #2 may be determined by external restriction of growth region.

Motivation: Motivation for this challenge is twofold: (1) Current synthetic circuits are limited in their ability to form self emerging spatial patterns in a robust manner. In fact, most current synthetic patterning circuits are driven by external cues. This challenge will likely push forward the technology for developing synthetic circuits based on cell‐cell communication (2) By constructing synthetic circuits exhibiting robust self emerging spatial patterns we can learn about the mechanisms involved in developmental patterning circuits. In particular, such a challenge would help explore the range of possible genetic circuits that can generate multicellular development and their limitations.

Impact: The impact of this challenge is twofold: (1) Improved understanding of basic engineering principles for synthetic biologists will enable more rapid and pervasive development of synthetic circuits, with applications in materials processing, environmental science, agriculture and medicine. (2) The ability to generate self emerging spatial patterns may be important in the field of tissue engineering where precise and accurate patterns of differentiation are required.

Metric(s): The winner of this challenge will be determined based on the difference between the observed mean spatial response function and an ideal spatial pattern. The ideal pattern for the concentric ring challenge ( #1) is on at a diameter of N (TBD) cells and turns off sharply at beyond that diameter. The ideal pattern for striped pattern challenge (#2) is an on and off patterns with a fixed wavelength of N (TBD) cells. Again, boundaries between on and off states should be sharp.

The following method will be used to determine the numerical score for each submission: let <amsmath>r_i(x)</amsmath> represent the ideal spatial response curve (for the concentric ring: Fmax for R<RN, 0 for R>RN, where RN represent the diameter of N cells, and Fmax is a maximal fluorescence level (determined by contestant)). Let <amsmath>y_i(x)</amsmath> represent the measured fluorescence of a given cell at steady state (time will be determined by contestant). Each run will be scored according to the formula:

<amsmath>

\text{ Score[run]} = \int_0^\infty |y_i(x) - r_i(x)|^2 dx

</amsmath>

A similar scoring method will be applied to the striped pattern.

The score for the submitted design will be the worst (highest) value of the score across 3 runs corresponding to 3 temperatures: nominal, nominal-5%, nominal+5% (where nominal is chosen by the contestant).