Xinnan Zhang

Xinnan Zhang, Jialin Wu, Junyi Xie et al.

The prediction modeling of drug-target interactions is crucial to drug discovery and design, which has seen rapid advancements owing to deep learning technologies. Recently developed methods, such as those based on graph neural networks (GNNs) and Transformers, demonstrate exceptional performance across various datasets by effectively extracting structural information. However, the benchmarking of these novel methods often varies significantly in terms of hyperparameter settings and datasets, which limits algorithmic progress. In view of these, we conducted a comprehensive survey and benchmark for drug-target interaction modeling from a structural perspective via integrating tens of explicit (i.e., GNN-based) and implicit (i.e., Transformer-based) structure learning algorithms. We conducted a macroscopical comparison between these two classes of encoding strategies as well as the different featurization techniques that inform molecules' chemical and physical properties. We then carry out the microscopical comparison between all the integrated models across the six datasets via comprehensively benchmarking their effectiveness and efficiency. To ensure fairness, we investigate model performance under individually optimized configuration. Remarkably, the summarized insights from the benchmark studies lead to the design of model combos. We demonstrate that our combos can achieve new state-of-the-art performance on various datasets associated with cost-effective memory and computation.

Kun Wang, Guibin Zhang, Xinnan Zhang et al.

Graph Neural Networks (GNNs) have become pivotal tools for a range of graph-based learning tasks. Notably, most current GNN architectures operate under the assumption of homophily, whether explicitly or implicitly. While this underlying assumption is frequently adopted, it is not universally applicable, which can result in potential shortcomings in learning effectiveness. In this paper, \textbf{for the first time}, we transfer the prevailing concept of ``one node one receptive field" to the heterophilic graph. By constructing a proxy label predictor, we enable each node to possess a latent prediction distribution, which assists connected nodes in determining whether they should aggregate their associated neighbors. Ultimately, every node can have its own unique aggregation hop and pattern, much like each snowflake is unique and possesses its own characteristics. Based on observations, we innovatively introduce the Heterophily Snowflake Hypothesis and provide an effective solution to guide and facilitate research on heterophilic graphs and beyond. We conduct comprehensive experiments including (1) main results on 10 graphs with varying heterophily ratios across 10 backbones; (2) scalability on various deep GNN backbones (SGC, JKNet, etc.) across various large number of layers (2,4,6,8,16,32 layers); (3) comparison with conventional snowflake hypothesis; (4) efficiency comparison with existing graph pruning algorithms. Our observations show that our framework acts as a versatile operator for diverse tasks. It can be integrated into various GNN frameworks, boosting performance in-depth and offering an explainable approach to choosing the optimal network depth. The source code is available at \url{https://github.com/bingreeky/HeteroSnoH}.

Xinnan Zhang, Chenliang Li, Siliang Zeng et al.

Aligning large language models (LLMs) with human preferences usually requires fine-tuning methods such as RLHF and DPO. These methods directly optimize the model parameters, so they cannot be used in test-time to improve model performance, nor are they applicable when the model weights are not accessible. In contrast, test-time methods sidestep weight updates by leveraging reward functions to guide and improve output quality. However, they incur high inference costs, and their one-shot guidance is often based on imperfect reward or value functions, leading to suboptimal outputs. In this work, we present a method named Iterative Reweight-then-Optimize (IRO), a reinforcement learning (RL) framework that performs RL-style alignment of the (frozen) base model without touching its parameters. During training, each iteration (i) samples candidates from the base model, (ii) resamples using current value functions, and (iii) trains a new lightweight value function that guides the next decoding pass. At test time, the value functions are used to guide the base model generation via a search-based optimization process. Notably, users can apply IRO to align a model on their own dataset, similar to OpenAI's reinforcement fine-tuning (RFT), but without requiring access to the model weights.