Junyi Li

Zheming Xing, Siyuan Zhou, Ruinan Wang et al.

Accurate prediction of synthetic lethality (SL) is important for guiding the development of cancer drugs and therapies. SL prediction faces significant challenges in the effective fusion of heterogeneous multi-source data. Existing multimodal methods often suffer from "modality laziness" due to disparate convergence speeds, which hinders the exploitation of complementary information. This is also one reason why most existing SL prediction models cannot perform well on both pan-cancer and single-cancer SL pair prediction. In this study, we propose SynLeaF, a dual-stage multimodal fusion framework for SL prediction across pan- and single-cancer contexts. The framework employs a VAE-based cross-encoder with a product of experts mechanism to fuse four omics data types (gene expression, mutation, methylation, and CNV), while simultaneously utilizing a relational graph convolutional network to capture structured gene representations from biomedical knowledge graphs. To mitigate modality laziness, SynLeaF introduces a dual-stage training mechanism employing featurelevel knowledge distillation with adaptive uni-modal teacher and ensemble strategies. In extensive experiments across eight specific cancer types and a pancancer dataset, SynLeaF achieves superior performance in 17 out of 19 scenarios. Ablation studies and gradient analyses further validate the critical contributions of the proposed fusion and distillation mechanisms to model robustness and generalization. To facilitate community use, a web server is available at https://synleaf.bioinformatics-lilab.cn.

Yuhuan Zhou, Yulin Wu, Weiwei Yuan et al.

Drug-target relationships may now be predicted computationally using bioinformatics data, which is a valuable tool for understanding pharmacological effects, enhancing drug development efficiency, and advancing related research. A number of structure-based, ligand-based and network-based approaches have now emerged. Furthermore, the integration of graph attention networks with intricate drug target studies is an application area of growing interest. In our work, we formulate a model called MKDTI by extracting kernel information from various layer embeddings of a graph attention network. This combination improves the prediction ability with respect to novel drug-target relationships. We first build a drug-target heterogeneous network using heterogeneous data of drugs and targets, and then use a self-enhanced multi-head graph attention network to extract potential features in each layer. Next, we utilize embeddings of each layer to computationally extract kernel matrices and fuse multiple kernel matrices. Finally, we use a Dual Laplacian Regularized Least Squares framework to forecast novel drug-target entity connections. This prediction can be facilitated by integrating the kernel matrix associated with the drug-target. We measured our model's efficacy using AUPR and AUC. Compared to the benchmark algorithms, our model outperforms them in the prediction outcomes. In addition, we conducted an experiment on kernel selection. The results show that the multi-kernel fusion approach combined with the kernel matrix generated by the graph attention network provides complementary insights into the model. The fusion of this information helps to enhance the accuracy of the predictions.

Junyi Li, Hwee Tou Ng

Despite their outstanding capabilities, large language models (LLMs) are prone to hallucination and producing factually incorrect information. This challenge has spurred efforts in attributed text generation, which prompts LLMs to generate content with supporting evidence. In this paper, we propose a novel framework, called Think&Cite, and formulate attributed text generation as a multi-step reasoning problem integrated with search. Specifically, we propose Self-Guided Monte Carlo Tree Search (SG-MCTS), which capitalizes on the self-reflection capability of LLMs to reason about the intermediate states of MCTS for guiding the tree expansion process. To provide reliable and comprehensive feedback, we introduce Progress Reward Modeling to measure the progress of tree search from the root to the current state from two aspects, i.e., generation and attribution progress. We conduct extensive experiments on three datasets and the results show that our approach significantly outperforms baseline approaches.