Dan Yu

Yanyi Chu, Dan Yu, Yupeng Li et al.

The 5' UTR, a regulatory region at the beginning of an mRNA molecule, plays a crucial role in regulating the translation process and impacts the protein expression level. Language models have showcased their effectiveness in decoding the functions of protein and genome sequences. Here, we introduced a language model for 5' UTR, which we refer to as the UTR-LM. The UTR-LM is pre-trained on endogenous 5' UTRs from multiple species and is further augmented with supervised information including secondary structure and minimum free energy. We fine-tuned the UTR-LM in a variety of downstream tasks. The model outperformed the best-known benchmark by up to 42% for predicting the Mean Ribosome Loading, and by up to 60% for predicting the Translation Efficiency and the mRNA Expression Level. The model also applies to identifying unannotated Internal Ribosome Entry Sites within the untranslated region and improves the AUPR from 0.37 to 0.52 compared to the best baseline. Further, we designed a library of 211 novel 5' UTRs with high predicted values of translation efficiency and evaluated them via a wet-lab assay. Experiment results confirmed that our top designs achieved a 32.5% increase in protein production level relative to well-established 5' UTR optimized for therapeutics.

Ran Wang, Karthikeya Parunandi, Dan Yu et al.

This paper addresses the problem of learning the optimal control policy for a nonlinear stochastic dynamical system with continuous state space, continuous action space and unknown dynamics. This class of problems are typically addressed in stochastic adaptive control and reinforcement learning literature using model-based and model-free approaches respectively. Both methods rely on solving a dynamic programming problem, either directly or indirectly, for finding the optimal closed loop control policy. The inherent `curse of dimensionality' associated with dynamic programming method makes these approaches also computationally difficult. This paper proposes a novel decoupled data-based control (D2C) algorithm that addresses this problem using a decoupled, `open loop - closed loop', approach. First, an open-loop deterministic trajectory optimization problem is solved using a black-box simulation model of the dynamical system. Then, a closed loop control is developed around this open loop trajectory by linearization of the dynamics about this nominal trajectory. By virtue of linearization, a linear quadratic regulator based algorithm can be used for this closed loop control. We show that the performance of D2C algorithm is approximately optimal. Moreover, simulation performance suggests significant reduction in training time compared to other state of the art algorithms.