Ziyang Chen
Publications
Can Broad Biomedical Knowledge be Contextualized into Scenario-Grounded Propositions?
Biomedical discovery often requires connecting broad biomedical knowledge with specific experimental or clinical data. Background knowledge suggests relevant mechanisms but is usually too general to map directly onto dataset variables, while data-driven patterns can be dataset-specific and hard to interpret mechanistically. We study this missing link as knowledge contextualization: transforming broad biomedical knowledge into evidence-supported, scenario-grounded propositions that domain experts can inspect, replay, and validate. We propose SCENE, a bi-level multi-agent framework that treats knowledge contextualization as iterative search. The upper level converts broad knowledge into search directions and grounds them in the dataset schema. The lower level executes these directions through multi-objective optimization to identify concrete propositions that balance evidential strength and data support. Feedback between the two levels progressively refines the search. We evaluate SCENE in two settings: discovering patient subgroups with heterogeneous treatment benefits in clinical trial scenarios, and identifying context-specific biological responses in LINCS L1000 studies. In clinical trials, SCENE discovers specific, well-supported subgroups and outperforms existing baselines. In L1000 studies, SCENE identifies perturbational contexts with strong target-response matching and high positive rates. These results show that SCENE bridges broad knowledge and scenario-specific evidence, producing traceable, inspectable hypotheses for follow-up validation.
Don't Retrain, Just Reuse: Recovering Dual-Target Molecules from Single-Target Diffusion Models
Designing a single molecule that modulates two targets is a promising strategy for polypharmacology, but it remains substantially harder than standard single-target generation because one candidate must satisfy two binding requirements while preserving drug-likeness and synthesizability. Existing dual-target generative methods typically introduce dual-target capability by either retraining the generator or intervening in the diffusion process during sampling. The former can be costly and difficult to stabilize when dual-target supervision is sparse, while the latter may be sensitive to denoising-time target balancing and competing update directions. These limitations motivate a generator-preserving alternative that keeps the pretrained prior intact: can dual-target candidates instead be recovered from the input space of a frozen single-target diffusion model, without modifying its parameters or denoising dynamics? We formulate this task as a constrained multi-objective optimization problem and propose REUSE, a hierarchical evolutionary input-space search framework that combines pair-conditioned exploration with structured multi-stage selection to enforce dual-target affinity, chemical quality, and diversity. Experiments show that, compared with methods that modify the diffusion process, REUSE consistently improves dual-target affinity and balance, achieving a 20.9-percentage-point gain in Dual High Affinity over the strongest prior baseline while maintaining competitive molecular quality.
PolicyLong: Towards On-Policy Context Extension
Extending LLM context windows is hindered by scarce high-quality long-context data. Recent methods synthesize data with genuine long-range dependencies via information-theoretic verification, selecting contexts that reduce a base model's predictive entropy. However, their single-pass offline construction with a fixed model creates a fundamental off-policy gap: the static screening landscape misaligns with the model's evolving capabilities, causing the training distribution to drift. We propose PolicyLong, shifting data construction towards a dynamic on-policy paradigm. By iteratively re-executing data screening (entropy computation, retrieval, and verification) using the current model, PolicyLong ensures the training distribution tracks evolving capabilities, yielding an emergent self-curriculum. Crucially, both positive and hard negative contexts derive from the current model's entropy landscape, co-evolving what the model learns to exploit and resist. Experiments on RULER, HELMET, and LongBench-v2 (Qwen2.5-3B) show PolicyLong consistently outperforms EntropyLong and NExtLong, with gains growing at longer contexts (e.g., +2.54 at 128K on RULER), confirming the value of on-policy data evolution.
On-Policy Supervised Fine-Tuning for Efficient Reasoning
Large reasoning models (LRMs) are commonly trained with reinforcement learning (RL) to explore long chain-of-thought reasoning, achieving strong performance at high computational cost. Recent methods add multi-reward objectives to jointly optimize correctness and brevity, but these complex extensions often destabilize training and yield suboptimal trade-offs. We revisit this objective and challenge the necessity of such complexity. Through principled analysis, we identify fundamental misalignments in this paradigm: KL regularization loses its intended role when correctness and length are directly verifiable, and group-wise normalization becomes ambiguous under multiple reward signals. By removing these two items and simplifying the reward to a truncation-based length penalty, we show that the optimization problem reduces to supervised fine-tuning on self-generated data filtered for both correctness and conciseness. We term this simplified training strategy on-policy SFT. Despite its simplicity, on-policy SFT consistently defines the accuracy-efficiency Pareto frontier. It reduces CoT length by up to 80 while maintaining original accuracy, surpassing more complex RL-based methods across five benchmarks. Furthermore, it significantly enhances training efficiency, reducing GPU memory usage by 50% and accelerating convergence by 70%. Our code is available at https://github.com/EIT-NLP/On-Policy-SFT.
LongBench Pro: A More Realistic and Comprehensive Bilingual Long-Context Evaluation Benchmark
The rapid expansion of context length in large language models (LLMs) has outpaced existing evaluation benchmarks. Current long-context benchmarks often trade off scalability and realism: synthetic tasks underrepresent real-world complexity, while fully manual annotation is costly to scale to extreme lengths and diverse scenarios. We present LongBench Pro, a more realistic and comprehensive bilingual benchmark of 1,500 naturally occurring long-context samples in English and Chinese spanning 11 primary tasks and 25 secondary tasks, with input lengths from 8k to 256k tokens. LongBench Pro supports fine-grained analysis with task-specific metrics and a multi-dimensional taxonomy of context requirement (full vs. partial dependency), length (six levels), and difficulty (four levels calibrated by model performance). To balance quality with scalability, we propose a Human-Model Collaborative Construction pipeline: frontier LLMs draft challenging questions and reference answers, along with design rationales and solution processes, to reduce the cost of expert verification. Experts then rigorously validate correctness and refine problematic cases. Evaluating 46 widely used long-context LLMs on LongBench Pro yields three findings: (1) long-context optimization contributes more to long-context comprehension than parameter scaling; (2) effective context length is typically shorter than the claimed context length, with pronounced cross-lingual misalignment; and (3) the "thinking" paradigm helps primarily models trained with native reasoning, while mixed-thinking designs offer a promising Pareto trade-off. In summary, LongBench Pro provides a robust testbed for advancing long-context understanding.