Xuan Lin

Xuan Lin, Lichang Dai, Yafang Zhou et al.

Recent advances and achievements of artificial intelligence (AI) as well as deep and graph learning models have established their usefulness in biomedical applications, especially in drug-drug interactions (DDIs). DDIs refer to a change in the effect of one drug to the presence of another drug in the human body, which plays an essential role in drug discovery and clinical research. DDIs prediction through traditional clinical trials and experiments is an expensive and time-consuming process. To correctly apply the advanced AI and deep learning, the developer and user meet various challenges such as the availability and encoding of data resources, and the design of computational methods. This review summarizes chemical structure based, network based, NLP based and hybrid methods, providing an updated and accessible guide to the broad researchers and development community with different domain knowledge. We introduce widely-used molecular representation and describe the theoretical frameworks of graph neural network models for representing molecular structures. We present the advantages and disadvantages of deep and graph learning methods by performing comparative experiments. We discuss the potential technical challenges and highlight future directions of deep and graph learning models for accelerating DDIs prediction.

Tianjun Pan, Xuan Lin, Wenyan Yang et al.

Rubric-based evaluation has become a prevailing paradigm for evaluating instruction following in large language models (LLMs). Despite its widespread use, the reliability of these rubric-level evaluations remains unclear, calling for meta-evaluation. However, prior meta-evaluation efforts largely focus on the response level, failing to assess the fine-grained judgment accuracy that rubric-based evaluation relies on. To bridge this gap, we introduce RubricEval. Our benchmark features: (1) the first rubric-level meta-evaluation benchmark for instruction following, (2) diverse instructions and responses spanning multiple categories and model sources, and (3) a substantial set of 3,486 quality-controlled instances, along with Easy/Hard subsets that better differentiates judge performance. Our experiments reveal that rubric-level judging remains far from solved: even GPT-4o, a widely adopted judge in instruction-following benchmarks, achieves only 55.97% on Hard subset. Considering evaluation paradigm, rubric-level evaluation outperforms checklist-level, explicit reasoning improves accuracy, and both together reduce inter-judge variance. Through our established rubric taxonomy, we further identify common failure modes and offer actionable insights for reliable instruction-following evaluation.

Yuki Shirai, Xuan Lin, Alexander Schperberg et al.

While motion planning of locomotion for legged robots has shown great success, motion planning for legged robots with dexterous multi-finger grasping is not mature yet. We present an efficient motion planning framework for simultaneously solving locomotion (e.g., centroidal dynamics), grasping (e.g., patch contact), and contact (e.g., gait) problems. To accelerate the planning process, we propose distributed optimization frameworks based on Alternating Direction Methods of Multipliers (ADMM) to solve the original large-scale Mixed-Integer NonLinear Programming (MINLP). The resulting frameworks use Mixed-Integer Quadratic Programming (MIQP) to solve contact and NonLinear Programming (NLP) to solve nonlinear dynamics, which are more computationally tractable and less sensitive to parameters. Also, we explicitly enforce patch contact constraints from limit surfaces with micro-spine grippers. We demonstrate our proposed framework in the hardware experiments, showing that the multi-limbed robot is able to realize various motions including free-climbing at a slope angle 45° with a much shorter planning time.

Yang Zhao, Xuan Lin, Wenqiang Xu et al.

In recent days, streaming technology has greatly promoted the development in the field of livestream. Due to the excessive length of livestream records, it's quite essential to extract highlight segments with the aim of effective reproduction and redistribution. Although there are lots of approaches proven to be effective in the highlight detection for other modals, the challenges existing in livestream processing, such as the extreme durations, large topic shifts, much irrelevant information and so forth, heavily hamper the adaptation and compatibility of these methods. In this paper, we formulate a new task Livestream Highlight Detection, discuss and analyze the difficulties listed above and propose a novel architecture AntPivot to solve this problem. Concretely, we first encode the original data into multiple views and model their temporal relations to capture clues in a hierarchical attention mechanism. Afterwards, we try to convert the detection of highlight clips into the search for optimal decision sequences and use the fully integrated representations to predict the final results in a dynamic-programming mechanism. Furthermore, we construct a fully-annotated dataset AntHighlight to instantiate this task and evaluate the performance of our model. The extensive experiments indicate the effectiveness and validity of our proposed method.

Qian Zhu, Xinnan Guo, Jingjing Huo et al.

Adapting Large Language Models (LLMs) to high-stakes vertical domains like insurance presents a significant challenge: scenarios demand strict adherence to complex regulations and business logic with zero tolerance for hallucinations. Existing approaches often suffer from a Competency Trade-off - sacrificing general intelligence for domain expertise - or rely heavily on RAG without intrinsic reasoning. To bridge this gap, we present INS-S1, an insurance-specific LLM family trained via a novel end-to-end alignment paradigm. Our approach features two methodological innovations: (1) A Verifiable Data Synthesis System that constructs hierarchical datasets for actuarial reasoning and compliance; and (2) A Progressive SFT-RL Curriculum Framework that integrates dynamic data annealing with a synergistic mix of Verified Reasoning (RLVR) and AI Feedback (RLAIF). By optimizing data ratios and reward signals, this framework enforces domain constraints while preventing catastrophic forgetting. Additionally, we release INSEva, the most comprehensive insurance benchmark to date (39k+ samples). Extensive experiments show that INS-S1 achieves SOTA performance on domain tasks, significantly outperforming DeepSeek-R1 and Gemini-2.5-Pro. Crucially, it maintains top-tier general capabilities and achieves a record-low 0.6% hallucination rate (HHEM). Our results demonstrate that rigorous domain specialization can be achieved without compromising general intelligence.

Xuan Lin, Qingrui Liu, Hongxin Xiang et al.

Chemical reaction and retrosynthesis prediction are fundamental tasks in drug discovery. Recently, large language models (LLMs) have shown potential in many domains. However, directly applying LLMs to these tasks faces two major challenges: (i) lacking a large-scale chemical synthesis-related instruction dataset; (ii) ignoring the close correlation between reaction and retrosynthesis prediction for the existing fine-tuning strategies. To address these challenges, we propose ChemDual, a novel LLM framework for accurate chemical synthesis. Specifically, considering the high cost of data acquisition for reaction and retrosynthesis, ChemDual regards the reaction-and-retrosynthesis of molecules as a related recombination-and-fragmentation process and constructs a large-scale of 4.4 million instruction dataset. Furthermore, ChemDual introduces an enhanced LLaMA, equipped with a multi-scale tokenizer and dual-task learning strategy, to jointly optimize the process of recombination and fragmentation as well as the tasks between reaction and retrosynthesis prediction. Extensive experiments on Mol-Instruction and USPTO-50K datasets demonstrate that ChemDual achieves state-of-the-art performance in both predictions of reaction and retrosynthesis, outperforming the existing conventional single-task approaches and the general open-source LLMs. Through molecular docking analysis, ChemDual generates compounds with diverse and strong protein binding affinity, further highlighting its strong potential in drug design.

Xuan Lin, Long Chen, Yile Wang et al.

Large language models (LLMs) are widely applied in various natural language processing tasks such as question answering and machine translation. However, due to the lack of labeled data and the difficulty of manual annotation for biochemical properties, the performance for molecule generation tasks is still limited, especially for tasks involving multi-properties constraints. In this work, we present a two-step framework PEIT (Property Enhanced Instruction Tuning) to improve LLMs for molecular-related tasks. In the first step, we use textual descriptions, SMILES, and biochemical properties as multimodal inputs to pre-train a model called PEIT-GEN, by aligning multi-modal representations to synthesize instruction data. In the second step, we fine-tune existing open-source LLMs with the synthesized data, the resulting PEIT-LLM can handle molecule captioning, text-based molecule generation, molecular property prediction, and our newly proposed multi-constraint molecule generation tasks. Experimental results show that our pre-trained PEIT-GEN outperforms MolT5 and BioT5 in molecule captioning, demonstrating modalities align well between textual descriptions, structures, and biochemical properties. Furthermore, PEIT-LLM shows promising improvements in multi-task molecule generation, proving the scalability of the PEIT framework for various molecular tasks. We release the code, constructed instruction data, and model checkpoints in https://github.com/chenlong164/PEIT.

Tengfei Ma, Yujie Chen, Wen Tao et al.

Molecular interaction prediction plays a crucial role in forecasting unknown interactions between molecules, such as drug-target interaction (DTI) and drug-drug interaction (DDI), which are essential in the field of drug discovery and therapeutics. Although previous prediction methods have yielded promising results by leveraging the rich semantics and topological structure of biomedical knowledge graphs (KGs), they have primarily focused on enhancing predictive performance without addressing the presence of inevitable noise and inconsistent semantics. This limitation has hindered the advancement of KG-based prediction methods. To address this limitation, we propose BioKDN (Biomedical Knowledge Graph Denoising Network) for robust molecular interaction prediction. BioKDN refines the reliable structure of local subgraphs by denoising noisy links in a learnable manner, providing a general module for extracting task-relevant interactions. To enhance the reliability of the refined structure, BioKDN maintains consistent and robust semantics by smoothing relations around the target interaction. By maximizing the mutual information between reliable structure and smoothed relations, BioKDN emphasizes informative semantics to enable precise predictions. Experimental results on real-world datasets show that BioKDN surpasses state-of-the-art models in DTI and DDI prediction tasks, confirming the effectiveness and robustness of BioKDN in denoising unreliable interactions within contaminated KGs

Mingwei Xu, Xuan Lin, Xinnan Guo et al.

While linear attention reduces the quadratic complexity of standard Transformers to linear time, it often lags behind in expressivity due to the removal of softmax normalization. This omission eliminates \emph{global competition}, a critical mechanism that enables models to sharply focus on relevant information amidst long-context noise. In this work, we propose \textbf{Softmax Linear Attention (SLA)}, a framework designed to restore this competitive selection without sacrificing efficiency. By lifting the softmax operation from the token level to the head level, SLA leverages attention heads as coarse semantic slots, applying a competitive gating mechanism to dynamically select the most relevant subspaces. This reintroduces the ``winner-take-all'' dynamics essential for precise retrieval and robust long-context understanding. Distinct from prior methods that focus on refining local kernel functions, SLA adopts a broader perspective by exploiting the higher-level multi-head aggregation structure. Extensive experiments demonstrate that SLA consistently enhances state-of-the-art linear baselines (RetNet, GLA, GDN) across language modeling and long-context benchmarks, particularly in challenging retrieval scenarios where it significantly boosts robustness against noise, validating its capability to restore precise focus while maintaining linear complexity.

Tengfei Ma, Xuan Lin, Tianle Li et al.

Large Language Models (LLMs) have recently demonstrated remarkable performance in general tasks across various fields. However, their effectiveness within specific domains such as drug development remains challenges. To solve these challenges, we introduce \textbf{Y-Mol}, forming a well-established LLM paradigm for the flow of drug development. Y-Mol is a multiscale biomedical knowledge-guided LLM designed to accomplish tasks across lead compound discovery, pre-clinic, and clinic prediction. By integrating millions of multiscale biomedical knowledge and using LLaMA2 as the base LLM, Y-Mol augments the reasoning capability in the biomedical domain by learning from a corpus of publications, knowledge graphs, and expert-designed synthetic data. The capability is further enriched with three types of drug-oriented instructions: description-based prompts from processed publications, semantic-based prompts for extracting associations from knowledge graphs, and template-based prompts for understanding expert knowledge from biomedical tools. Besides, Y-Mol offers a set of LLM paradigms that can autonomously execute the downstream tasks across the entire process of drug development, including virtual screening, drug design, pharmacological properties prediction, and drug-related interaction prediction. Our extensive evaluations of various biomedical sources demonstrate that Y-Mol significantly outperforms general-purpose LLMs in discovering lead compounds, predicting molecular properties, and identifying drug interaction events.

Dan Luo, Jinyu Zhou, Le Xu et al.

Predicting drug-target binding affinity (DTA) is essential for identifying potential therapeutic candidates in drug discovery. However, most existing models rely heavily on static protein structures, often overlooking the dynamic nature of proteins, which is crucial for capturing conformational flexibility that will be beneficial for protein binding interactions. We introduce DynamicDTA, an innovative deep learning framework that incorporates static and dynamic protein features to enhance DTA prediction. The proposed DynamicDTA takes three types of inputs, including drug sequence, protein sequence, and dynamic descriptors. A molecular graph representation of the drug sequence is generated and subsequently processed through graph convolutional network, while the protein sequence is encoded using dilated convolutions. Dynamic descriptors, such as root mean square fluctuation, are processed through a multi-layer perceptron. These embedding features are fused with static protein features using cross-attention, and a tensor fusion network integrates all three modalities for DTA prediction. Extensive experiments on three datasets demonstrate that DynamicDTA achieves by at least 3.4% improvement in RMSE score with comparison to seven state-of-the-art baseline methods. Additionally, predicting novel drugs for Human Immunodeficiency Virus Type 1 and visualizing the docking complexes further demonstrates the reliability and biological relevance of DynamicDTA.

Tengfei Ma, Yujie Chen, Liang Wang et al.

Inductive Knowledge Graph Completion (KGC) aims to infer missing facts between newly emerged entities within knowledge graphs (KGs), posing a significant challenge. While recent studies have shown promising results in inferring such entities through knowledge subgraph reasoning, they suffer from (i) the semantic inconsistencies of similar relations, and (ii) noisy interactions inherent in KGs due to the presence of unconvincing knowledge for emerging entities. To address these challenges, we propose a Semantic Structure-aware Denoising Network (S$^2$DN) for inductive KGC. Our goal is to learn adaptable general semantics and reliable structures to distill consistent semantic knowledge while preserving reliable interactions within KGs. Specifically, we introduce a semantic smoothing module over the enclosing subgraphs to retain the universal semantic knowledge of relations. We incorporate a structure refining module to filter out unreliable interactions and offer additional knowledge, retaining robust structure surrounding target links. Extensive experiments conducted on three benchmark KGs demonstrate that S$^2$DN surpasses the performance of state-of-the-art models. These results demonstrate the effectiveness of S$^2$DN in preserving semantic consistency and enhancing the robustness of filtering out unreliable interactions in contaminated KGs.

Xiaoqin Pan, Xuan Lin, Dongsheng Cao et al.

Drug development is time-consuming and expensive. Repurposing existing drugs for new therapies is an attractive solution that accelerates drug development at reduced experimental costs, specifically for Coronavirus Disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, comprehensively obtaining and productively integrating available knowledge and big biomedical data to effectively advance deep learning models is still challenging for drug repurposing in other complex diseases. In this review, we introduce guidelines on how to utilize deep learning methodologies and tools for drug repurposing. We first summarized the commonly used bioinformatics and pharmacogenomics databases for drug repurposing. Next, we discuss recently developed sequence-based and graph-based representation approaches as well as state-of-the-art deep learning-based methods. Finally, we present applications of drug repurposing to fight the COVID-19 pandemic, and outline its future challenges.

Xuan Lin, Gabriel I. Fernandez, Dennis W. Hong

Mixed integer convex and nonlinear programs, MICP and MINLP, are expressive but require long solving times. Recent work that combines learning methods on solver heuristics has shown potential to overcome this issue allowing for applications on larger scale practical problems. Gathering sufficient training data to employ these methods still present a challenge since getting data from traditional solvers are slow and newer learning approaches still require large amounts of data. In order to scale up and make these hybrid learning approaches more manageable we propose ReDUCE, a method that exploits structure within small to medium size datasets. We also introduce the bookshelf organization problem as an MINLP as a way to measure performance of solvers with ReDUCE. Results show that existing algorithms with ReDUCE can solve this problem within a few seconds, a significant improvement over the original formulation. ReDUCE is demonstrated as a high level planner for a robotic arm for the bookshelf problem.

Yusuke Tanaka, Yuki Shirai, Zachary Lacey et al.

Current rigid linkage grippers are limited in flexibility, and gripper design optimality relies on expertise, experiments, or arbitrary parameters. Our proposed rigid gripper can accommodate irregular and off-center objects through a whippletree mechanism, improving adaptability. We present a whippletree-based rigid under-actuated gripper and its parametric design multi-objective optimization for a one-wall climbing task. Our proposed objective function considers kinematics and grasping forces simultaneously with a mathematical metric based on a model of an object environment. Our multi-objective problem is formulated as a single kinematic objective function with auto-tuning force-based weight. Our results indicate that our proposed objective function determines optimal parameters and kinematic ranges for our under-actuated gripper in the task environment with sufficient grasping forces.

Xuan Lin, Min Sung Ahn, Dennis Hong

For multi-limbed robots, motion planning with posture and force constraints tends to be a difficult optimization problem due to nonlinearities, which also present extended solve times. We propose a multi-stage optimization framework with data-driven inter-stage coupling constraints to address the nonlinearity. Both clustering and evolutionary approaches to find the McCormick envelope relaxations are used to find the problem-specific parameters. The learned constraints are then used in the prior stages, which provides advanced knowledge of the following stages. This leads to improved solve times and interpretability of the results. The planner is validated through multiple walking and climbing tasks on a 10 kg hexapod robot.

Jingwen Zhang, Xuan Lin, Dennis W Hong

In order to achieve autonomous vertical wall climbing, the transition phase from the ground to the wall requires extra consideration inevitably. This paper focuses on the contact sequence planner to transition between flat terrain and vertical surfaces for multi-limbed climbing robots. To overcome the transition phase, it requires planning both multi-contact and contact wrenches simultaneously which makes it difficult. Instead of using a predetermined contact sequence, we consider various motions on different environment setups via modeling contact constraints and limb switchability as complementarity conditions. Two safety factors for toe sliding and motor over-torque are the main tuning parameters for different contact sequences. By solving as a nonlinear program (NLP), we can generate several feasible sequences of foot placements and contact forces to avoid failure cases. We verified feasibility with demonstrations on the hardware SiLVIA, a six-legged robot capable of vertically climbing between two walls by bracing itself in-between using only friction.

Yuki Shirai, Xuan Lin, Ankur Mehta et al.

Although Trajectory Optimization (TO) is one of the most powerful motion planning tools, it suffers from expensive computational complexity as a time horizon increases in cluttered environments. It can also fail to converge to a globally optimal solution. In this paper, we present Lazy Trajectory Optimization (LTO) that unifies local short-horizon TO and global Graph-Search Planning (GSP) to generate a long-horizon global optimal trajectory. LTO solves TO with the same constraints as the original long-horizon TO with improved time complexity. We also propose a TO-aware cost function that can balance both solution cost and planning time. Since LTO solves many nearly identical TO in a roadmap, it can provide an informed warm-start for TO to accelerate the planning process. We also present proofs of the computational complexity and optimality of LTO. Finally, we demonstrate LTO's performance on motion planning problems for a 2 DOF free-flying robot and a 21 DOF legged robot, showing that LTO outperforms existing algorithms in terms of its runtime and reliability.

Xuan Lin

Accurately predicting drug-target binding affinity (DTA) in silico is a key task in drug discovery. Most of the conventional DTA prediction methods are simulation-based, which rely heavily on domain knowledge or the assumption of having the 3D structure of the targets, which are often difficult to obtain. Meanwhile, traditional machine learning-based methods apply various features and descriptors, and simply depend on the similarities between drug-target pairs. Recently, with the increasing amount of affinity data available and the success of deep representation learning models on various domains, deep learning techniques have been applied to DTA prediction. However, these methods consider either label/one-hot encodings or the topological structure of molecules, without considering the local chemical context of amino acids and SMILES sequences. Motivated by this, we propose a novel end-to-end learning framework, called DeepGS, which uses deep neural networks to extract the local chemical context from amino acids and SMILES sequences, as well as the molecular structure from the drugs. To assist the operations on the symbolic data, we propose to use advanced embedding techniques (i.e., Smi2Vec and Prot2Vec) to encode the amino acids and SMILES sequences to a distributed representation. Meanwhile, we suggest a new molecular structure modeling approach that works well under our framework. We have conducted extensive experiments to compare our proposed method with state-of-the-art models including KronRLS, SimBoost, DeepDTA and DeepCPI. Extensive experimental results demonstrate the superiorities and competitiveness of DeepGS.

Xuan Lin, Jingwen Zhang, Junjie Shen et al.

Motion planning trajectories for a multi-limbed robot to climb up walls requires a unique combination of constraints on torque, contact force, and posture. This paper focuses on motion planning for one particular setup wherein a six-legged robot braces itself between two vertical walls and climbs vertically with end effectors that only use friction. Instead of motion planning with a single nonlinear programming (NLP) solver, we decoupled the problem into two parts with distinct physical meaning: torso postures and contact forces. The first part can be formulated as either a mixed-integer convex programming (MICP) or NLP problem, while the second part is formulated as a series of standard convex optimization problems. Variants of the two wall climbing problem e.g., obstacle avoidance, uneven surfaces, and angled walls, help verify the proposed method in simulation and experimentation.