Small Molecule Drug Discovery Through Deep Learning:Progress, Challenges, and Opportunities

Due to their excellent drug-like and pharmacokinetic properties, small molecule drugs are widely used to treat various diseases, making them a critical component of drug discovery. In recent years, with the rapid development of deep learning (DL) techniques, DL-based small molecule drug discovery methods have achieved excellent performance in prediction accuracy, speed, and complex molecular relationship modeling compared to traditional machine learning approaches. These advancements enhance drug screening efficiency and optimization, and they provide more precise and effective solutions for various drug discovery tasks. Contributing to this field's development, this paper aims to systematically summarize and generalize the recent key tasks and representative techniques in DL-based small molecule drug discovery in recent years. Specifically, we provide an overview of the major tasks in small molecule drug discovery and their interrelationships. Next, we analyze the six core tasks, summarizing the related methods, commonly used datasets, and technological development trends. Finally, we discuss key challenges, such as interpretability and out-of-distribution generalization, and offer our insights into future research directions for DL-assisted small molecule drug discovery.

UniRestorer: Universal Image Restoration via Adaptively Estimating Image Degradation at Proper Granularity

Recently, considerable progress has been made in allin-one image restoration. Generally, existing methods can be degradation-agnostic or degradation-aware. However, the former are limited in leveraging degradation-specific restoration, and the latter suffer from the inevitable error in degradation estimation. Consequently, the performance of existing methods has a large gap compared to specific single-task models. In this work, we make a step forward in this topic, and present our UniRestorer with improved restoration performance. Specifically, we perform hierarchical clustering on degradation space, and train a multi-granularity mixture-of-experts (MoE) restoration model. Then, UniRestorer adopts both degradation and granularity estimation to adaptively select an appropriate expert for image restoration. In contrast to existing degradation-agnostic and -aware methods, UniRestorer can leverage degradation estimation to benefit degradationspecific restoration, and use granularity estimation to make the model robust to degradation estimation error. Experimental results show that our UniRestorer outperforms stateof-the-art all-in-one methods by a large margin, and is promising in closing the performance gap to specific single task models. The code and pre-trained models will be publicly available at https://github.com/mrluin/UniRestorer.

VitaGlyph: Vitalizing Artistic Typography with Flexible Dual-branch Diffusion Models

Artistic typography is a technique to visualize the meaning of input character in an imaginable and readable manner. With powerful text-to-image diffusion models, existing methods directly design the overall geometry and texture of input character, making it challenging to ensure both creativity and legibility. In this paper, we introduce a dual-branch and training-free method, namely VitaGlyph, enabling flexible artistic typography along with controllable geometry change to maintain the readability. The key insight of VitaGlyph is to treat input character as a scene composed of Subject and Surrounding, followed by rendering them under varying degrees of geometry transformation. The subject flexibly expresses the essential concept of input character, while the surrounding enriches relevant background without altering the shape. Specifically, we implement VitaGlyph through a three-phase framework: (i) Knowledge Acquisition leverages large language models to design text descriptions of subject and surrounding. (ii) Regional decomposition detects the part that most matches the subject description and divides input glyph image into subject and surrounding regions. (iii) Typography Stylization firstly refines the structure of subject region via Semantic Typography, and then separately renders the textures of Subject and Surrounding regions through Controllable Compositional Generation. Experimental results demonstrate that VitaGlyph not only achieves better artistry and readability, but also manages to depict multiple customize concepts, facilitating more creative and pleasing artistic typography generation. Our code will be made publicly at https://github.com/Carlofkl/VitaGlyph.

Small Agent Can Also Rock! Empowering Small Language Models as Hallucination Detector

Hallucination detection is a challenging task for large language models (LLMs), and existing studies heavily rely on powerful closed-source LLMs such as GPT-4. In this paper, we propose an autonomous LLM-based agent framework, called HaluAgent, which enables relatively smaller LLMs (e.g. Baichuan2-Chat 7B) to actively select suitable tools for detecting multiple hallucination types such as text, code, and mathematical expression. In HaluAgent, we integrate the LLM, multi-functional toolbox, and design a fine-grained three-stage detection framework along with memory mechanism. To facilitate the effectiveness of HaluAgent, we leverage existing Chinese and English datasets to synthesize detection trajectories for fine-tuning, which endows HaluAgent with the capability for bilingual hallucination detection. Extensive experiments demonstrate that only using 2K samples for tuning LLMs, HaluAgent can perform hallucination detection on various types of tasks and datasets, achieving performance comparable to or even higher than GPT-4 without tool enhancements on both in-domain and out-of-domain datasets. We release our dataset and code at https://github.com/RUCAIBox/HaluAgent.

Decoding at the Speed of Thought: Harnessing Parallel Decoding of Lexical Units for LLMs

Large language models have demonstrated exceptional capability in natural language understanding and generation. However, their generation speed is limited by the inherently sequential nature of their decoding process, posing challenges for real-time applications. This paper introduces Lexical Unit Decoding (LUD), a novel decoding methodology implemented in a data-driven manner, accelerating the decoding process without sacrificing output quality. The core of our approach is the observation that a pre-trained language model can confidently predict multiple contiguous tokens, forming the basis for a \textit{lexical unit}, in which these contiguous tokens could be decoded in parallel. Extensive experiments validate that our method substantially reduces decoding time while maintaining generation quality, i.e., 33\% speed up on natural language generation with no quality loss, and 30\% speed up on code generation with a negligible quality loss of 3\%. Distinctively, LUD requires no auxiliary models and does not require changes to existing architectures. It can also be integrated with other decoding acceleration methods, thus achieving an even more pronounced inference efficiency boost. We posit that the foundational principles of LUD could define a new decoding paradigm for future language models, enhancing their applicability for a broader spectrum of applications. All codes are be publicly available at https://github.com/tjunlp-lab/Lexical-Unit-Decoding-LUD-. Keywords: Parallel Decoding, Lexical Unit Decoding, Large Language Model

A Cross-Field Fusion Strategy for Drug-Target Interaction Prediction

Drug-target interaction (DTI) prediction is a critical component of the drug discovery process. In the drug development engineering field, predicting novel drug-target interactions is extremely crucial.However, although existing methods have achieved high accuracy levels in predicting known drugs and drug targets, they fail to utilize global protein information during DTI prediction. This leads to an inability to effectively predict interaction the interactions between novel drugs and their targets. As a result, the cross-field information fusion strategy is employed to acquire local and global protein information. Thus, we propose the siamese drug-target interaction SiamDTI prediction method, which utilizes a double channel network structure for cross-field supervised learning.Experimental results on three benchmark datasets demonstrate that SiamDTI achieves higher accuracy levels than other state-of-the-art (SOTA) methods on novel drugs and targets.Additionally, SiamDTI's performance with known drugs and targets is comparable to that of SOTA approachs. The code is available at https://anonymous.4open.science/r/DDDTI-434D.

MasterWeaver: Taming Editability and Identity for Personalized Text-to-Image Generation

Text-to-image (T2I) diffusion models have shown significant success in personalized text-to-image generation, which aims to generate novel images with human identities indicated by the reference images. Despite promising identity fidelity has been achieved by several tuning-free methods, they usually suffer from overfitting issues. The learned identity tends to entangle with irrelevant information, resulting in unsatisfied text controllability, especially on faces. In this work, we present MasterWeaver, a test-time tuning-free method designed to generate personalized images with both faithful identity fidelity and flexible editability. Specifically, MasterWeaver adopts an encoder to extract identity features and steers the image generation through additional introduced cross attention. To improve editability while maintaining identity fidelity, we propose an editing direction loss for training, which aligns the editing directions of our MasterWeaver with those of the original T2I model. Additionally, a face-augmented dataset is constructed to facilitate disentangled identity learning, and further improve the editability. Extensive experiments demonstrate that our MasterWeaver can not only generate personalized images with faithful identity, but also exhibit superiority in text controllability. Our code will be publicly available at https://github.com/csyxwei/MasterWeaver.

Beyond the Sequence: Statistics-Driven Pre-training for Stabilizing Sequential Recommendation Model

The sequential recommendation task aims to predict the item that user is interested in according to his/her historical action sequence. However, inevitable random action, i.e. user randomly accesses an item among multiple candidates or clicks several items at random order, cause the sequence fails to provide stable and high-quality signals. To alleviate the issue, we propose the StatisTics-Driven Pre-traing framework (called STDP briefly). The main idea of the work lies in the exploration of utilizing the statistics information along with the pre-training paradigm to stabilize the optimization of recommendation model. Specifically, we derive two types of statistical information: item co-occurrence across sequence and attribute frequency within the sequence. And we design the following pre-training tasks: 1) The co-occurred items prediction task, which encourages the model to distribute its attention on multiple suitable targets instead of just focusing on the next item that may be unstable. 2) We generate a paired sequence by replacing items with their co-occurred items and enforce its representation close with the original one, thus enhancing the model's robustness to the random noise. 3) To reduce the impact of random on user's long-term preferences, we encourage the model to capture sequence-level frequent attributes. The significant improvement over six datasets demonstrates the effectiveness and superiority of the proposal, and further analysis verified the generalization of the STDP framework on other models.

FedPIT: Towards Privacy-preserving and Few-shot Federated Instruction Tuning

Instruction tuning has proven essential for enhancing the performance of large language models (LLMs) in generating human-aligned responses. However, collecting diverse, high-quality instruction data for tuning poses challenges, particularly in privacy-sensitive domains. Federated instruction tuning (FedIT) has emerged as a solution, leveraging federated learning from multiple data owners while preserving privacy. Yet, it faces challenges due to limited instruction data and vulnerabilities to training data extraction attacks. To address these issues, we propose a novel federated algorithm, FedPIT, which utilizes LLMs' in-context learning capability to self-generate task-specific synthetic data for training autonomously. Our method employs parameter-isolated training to maintain global parameters trained on synthetic data and local parameters trained on augmented local data, effectively thwarting data extraction attacks. Extensive experiments on real-world medical data demonstrate the effectiveness of FedPIT in improving federated few-shot performance while preserving privacy and robustness against data heterogeneity.

Chain-of-Specificity: An Iteratively Refining Method for Eliciting Knowledge from Large Language Models

Large Language Models (LLMs) exhibit remarkable generative capabilities, enabling the generation of valuable information. Despite these advancements, previous research found that LLMs sometimes struggle with adhering to specific constraints (e.g., in specific place or at specific time), at times even overlooking them, which leads to responses that are either too generic or not fully satisfactory. Existing approaches attempted to address this issue by decomposing or rewriting input instructions, yet they fall short in adequately emphasizing specific constraints and in unlocking the underlying knowledge (e.g., programming within the context of software development). In response, this paper proposes a simple yet effective method named Chain-of-Specificity (CoS). Specifically, CoS iteratively emphasizes the specific constraints in the input instructions, unlocks knowledge within LLMs, and refines responses. Experiments conducted on publicly available and self-build complex datasets demonstrate that CoS outperforms existing methods in enhancing generated content especially for the specificity. Besides, as the number of specific constraints increase, other baselines falter, while CoS still performs well. Moreover, we show that distilling responses generated by CoS effectively enhances the ability of smaller models to follow the constrained instructions. Resources of this paper will be released for further research.