Challenges can be seen as a type of game that motivates participants to solve serious tasks. As a result, competition organizers must develop effective game rules. However, these rules have multiple objectives beyond making the game enjoyable for participants. These objectives may include solving real-world problems, advancing scientific or technical areas, making scientific discoveries, and educating the public. In many ways, creating a challenge is similar to launching a product. It requires the same level of excitement and rigorous testing, and the goal is to attract ''customers'' in the form of participants. The process begins with a solid plan, such as a competition proposal that will eventually be submitted to an international conference and subjected to peer review. Although peer review does not guarantee quality, it does force organizers to consider the impact of their challenge, identify potential oversights, and generally improve its quality. This chapter provides guidelines for creating a strong plan for a challenge. The material draws on the preparation guidelines from organizations such as Kaggle 1 , ChaLearn 2 and Tailor 3 , as well as the NeurIPS proposal template, which some of the authors contributed to.

Messenger RNA-based medicines hold immense potential, as evidenced by their rapid deployment as COVID-19 vaccines. However, worldwide distribution of mRNA molecules has been limited by their thermostability, which is fundamentally limited by the intrinsic instability of RNA molecules to a chemical degradation reaction called in-line hydrolysis. Predicting the degradation of an RNA molecule is a key task in designing more stable RNA-based therapeutics. Here, we describe a crowdsourced machine learning competition ("Stanford OpenVaccine") on Kaggle, involving single-nucleotide resolution measurements on 6043 102-130-nucleotide diverse RNA constructs that were themselves solicited through crowdsourcing on the RNA design platform Eterna. The entire experiment was completed in less than 6 months. Winning models demonstrated test set errors that were better by 50% than the previous state-of-the-art DegScore model. Furthermore, these models generalized to blindly predicting orthogonal degradation data on much longer mRNA molecules (504-1588 nucleotides) with improved accuracy over DegScore and other models. Top teams integrated natural language processing architectures and data augmentation techniques with predictions from previous dynamic programming models for RNA secondary structure. These results indicate that such models are capable of representing in-line hydrolysis with excellent accuracy, supporting their use for designing stabilized messenger RNAs. The integration of two crowdsourcing platforms, one for data set creation and another for machine learning, may be fruitful for other urgent problems that demand scientific discovery on rapid timescales.