Retrieval-Enhanced Mutation Mastery: Augmenting Zero-Shot Prediction of Protein Language Model

Enzyme engineering enables the modification of wild-type proteins to meet industrial and research demands by enhancing catalytic activity, stability, binding affinities, and other properties. The emergence of deep learning methods for protein modeling has demonstrated superior results at lower costs compared to traditional approaches such as directed evolution and rational design. In mutation effect prediction, the key to pre-training deep learning models lies in accurately interpreting the complex relationships among protein sequence, structure, and function. This study introduces a retrieval-enhanced protein language model for comprehensive analysis of native properties from sequence and local structural interactions, as well as evolutionary properties from retrieved homologous sequences. The state-of-the-art performance of the proposed ProtREM is validated on over 2 million mutants across 217 assays from an open benchmark (ProteinGym). We also conducted post-hoc analyses of the model's ability to improve the stability and binding affinity of a VHH antibody. Additionally, we designed 10 new mutants on a DNA polymerase and conducted wet-lab experiments to evaluate their enhanced activity at higher temperatures. Both in silico and experimental evaluations confirmed that our method provides reliable predictions of mutation effects, offering an auxiliary tool for biologists aiming to evolve existing enzymes. The implementation is publicly available at https://github.com/tyang816/ProtREM.

Refining Packing and Shuffling Strategies for Enhanced Performance in Generative Language Models

Packing and shuffling tokens is a common practice in training auto-regressive language models (LMs) to prevent overfitting and improve efficiency. Typically documents are concatenated to chunks of maximum sequence length (MSL) and then shuffled. However setting the atom size, the length for each data chunk accompanied by random shuffling, to MSL may lead to contextual incoherence due to tokens from different documents being packed into the same chunk. An alternative approach is to utilize padding, another common data packing strategy, to avoid contextual incoherence by only including one document in each shuffled chunk. To optimize both packing strategies (concatenation vs padding), we investigated the optimal atom size for shuffling and compared their performance and efficiency. We found that matching atom size to MSL optimizes performance for both packing methods (concatenation and padding), and padding yields lower final perplexity (higher performance) than concatenation at the cost of more training steps and lower compute efficiency. This trade-off informs the choice of packing methods in training language models.

Towards CausalGPT: A Multi-Agent Approach for Faithful Knowledge Reasoning via Promoting Causal Consistency in LLMs

Despite advancements in LLMs, knowledge-based reasoning remains a longstanding issue due to the fragility of knowledge recall and inference. Existing methods primarily encourage LLMs to autonomously plan and solve problems or to extensively sample reasoning chains without addressing the conceptual and inferential fallacies. Attempting to alleviate inferential fallacies and drawing inspiration from multi-agent collaboration, we present a framework to increase faithfulness and causality for knowledge-based reasoning. Specifically, we propose to employ multiple intelligent agents (i.e., reasoners and an evaluator) to work collaboratively in a reasoning-and-consensus paradigm for elevated reasoning faithfulness. The reasoners focus on providing solutions with human-like causality to solve open-domain problems. On the other hand, the \textit{evaluator} agent scrutinizes if a solution is deducible from a non-causal perspective and if it still holds when challenged by a counterfactual candidate. According to the extensive and comprehensive evaluations on a variety of knowledge reasoning tasks (e.g., science question answering and commonsense reasoning), our framework outperforms all compared state-of-the-art approaches by large margins.

Formation Flight in Dense Environments

Formation flight has a vast potential for aerial robot swarms in various applications. However, existing methods lack the capability to achieve fully autonomous large-scale formation flight in dense environments. To bridge the gap, we present a complete formation flight system that effectively integrates real-world constraints into aerial formation navigation. This paper proposes a differentiable graph-based metric to quantify the overall similarity error between formations. This metric is invariant to rotation, translation, and scaling, providing more freedom for formation coordination. We design a distributed trajectory optimization framework that considers formation similarity, obstacle avoidance, and dynamic feasibility. The optimization is decoupled to make large-scale formation flights computationally feasible. To improve the elasticity of formation navigation in highly constrained scenes, we present a swarm reorganization method which adaptively adjusts the formation parameters and task assignments by generating local navigation goals. A novel swarm agreement strategy called global-remap-local-replan and a formation-level path planner is proposed in this work to coordinate the swarm global planning and local trajectory optimizations efficiently. To validate the proposed method, we design comprehensive benchmarks and simulations with other cutting-edge works in terms of adaptability, predictability, elasticity, resilience, and efficiency. Finally, integrated with palm-sized swarm platforms with onboard computers and sensors, the proposed method demonstrates its efficiency and robustness by achieving the largest scale formation flight in dense outdoor environments.