Ruilin Wang

Yang Tan, Ruilin Wang, Banghao Wu et al.

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.

Ziyi Tang, Ruilin Wang, Weixing Chen et al.

Despite the progress of foundation models, knowledge-based reasoning remains a persistent challenge due to their limited capacity for knowledge recall and inference. Existing methods primarily focus on encouraging these models to plan and solve problems or extensively sample reasoning chains independently. However, these methods often overlook conceptual errors and inferential fallacies, inevitably leading to a series of notorious issues such as misleading conclusions, cognitive biases, and reduced decision quality. While explicit modeling of causality is argued to hold promise in addressing these issues, contemporary research efforts have thus far fallen short in achieving causality-based foundation models. Drawing inspiration from the orchestration of diverse specialized agents collaborating to tackle intricate tasks, we propose a framework named Causal-Consistency Chain-of-Thought (CaCo-CoT) that harnesses multi-agent collaboration to bolster the faithfulness and causality of foundation models, involving a set of reasoners and evaluators. These agents collaboratively work within a reasoning-and-consensus paradigm to improve faithfulness. The reasoners are tasked with generating reasoning chains for knowledge-intensive problems by mimicking human causal reasoning. Meanwhile, the evaluator scrutinizes the causal consistency of a reasoner's reasoning chain from a non-causal and a counterfactual perspective. Our framework demonstrates significant superiority over state-of-the-art methods through extensive and comprehensive evaluations across text-based and multi-modal knowledge reasoning tasks (e.g., science question answering and commonsense reasoning).

Yang Tan, Chen Liu, Jingyuan Gao et al.

Natural language processing (NLP) has significantly influenced scientific domains beyond human language, including protein engineering, where pre-trained protein language models (PLMs) have demonstrated remarkable success. However, interdisciplinary adoption remains limited due to challenges in data collection, task benchmarking, and application. This work presents VenusFactory, a versatile engine that integrates biological data retrieval, standardized task benchmarking, and modular fine-tuning of PLMs. VenusFactory supports both computer science and biology communities with choices of both a command-line execution and a Gradio-based no-code interface, integrating $40+$ protein-related datasets and $40+$ popular PLMs. All implementations are open-sourced on https://github.com/tyang816/VenusFactory.

Yanbing Chen, Ruilin Wang, Zihao Yang et al.

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.

Wentao Wan, Zhuojie Yang, Yongcan Chen et al.

Deductive reasoning is a crucial logical capability that assists us in solving complex problems based on existing knowledge. Although augmented by Chain-of-Thought prompts, Large Language Models (LLMs) might not follow the correct reasoning paths. Enhancing the deductive reasoning abilities of LLMs, and leveraging their extensive built-in knowledge for various reasoning tasks, remains an open question. Attempting to mimic the human deductive reasoning paradigm, we propose a multi-stage Syllogistic-Reasoning Framework of Thought (SR-FoT) that enables LLMs to perform syllogistic deductive reasoning to handle complex knowledge-based reasoning tasks. Our SR-FoT begins by interpreting the question and then uses the interpretation and the original question to propose a suitable major premise. It proceeds by generating and answering minor premise questions in two stages to match the minor premises. Finally, it guides LLMs to use the previously generated major and minor premises to perform syllogistic deductive reasoning to derive the answer to the original question. Extensive and thorough experiments on knowledge-based reasoning tasks have demonstrated the effectiveness and advantages of our SR-FoT.

Tianshuo Xu, Peng Mi, Ruilin Wang et al.

Diffusion models (DMs) are a powerful generative framework that have attracted significant attention in recent years. However, the high computational cost of training DMs limits their practical applications. In this paper, we start with a consistency phenomenon of DMs: we observe that DMs with different initializations or even different architectures can produce very similar outputs given the same noise inputs, which is rare in other generative models. We attribute this phenomenon to two factors: (1) the learning difficulty of DMs is lower when the noise-prediction diffusion model approaches the upper bound of the timestep (the input becomes pure noise), where the structural information of the output is usually generated; and (2) the loss landscape of DMs is highly smooth, which implies that the model tends to converge to similar local minima and exhibit similar behavior patterns. This finding not only reveals the stability of DMs, but also inspires us to devise two strategies to accelerate the training of DMs. First, we propose a curriculum learning based timestep schedule, which leverages the noise rate as an explicit indicator of the learning difficulty and gradually reduces the training frequency of easier timesteps, thus improving the training efficiency. Second, we propose a momentum decay strategy, which reduces the momentum coefficient during the optimization process, as the large momentum may hinder the convergence speed and cause oscillations due to the smoothness of the loss landscape. We demonstrate the effectiveness of our proposed strategies on various models and show that they can significantly reduce the training time and improve the quality of the generated images.