Tong Pan

Zhikang Wang, Yue Bi, Tong Pan et al.

Multiple instance learning (MIL) is a powerful approach to classify whole slide images (WSIs) for diagnostic pathology. A fundamental challenge of MIL on WSI classification is to discover the \textit{critical instances} that trigger the bag label. However, previous methods are primarily designed under the independent and identical distribution hypothesis (\textit{i.i.d}), ignoring either the correlations between instances or heterogeneity of tumours. In this paper, we propose a novel multiplex-detection-based multiple instance learning (MDMIL) to tackle the issues above. Specifically, MDMIL is constructed by the internal query generation module (IQGM) and the multiplex detection module (MDM) and assisted by the memory-based contrastive loss during training. Firstly, IQGM gives the probability of instances and generates the internal query (IQ) for the subsequent MDM by aggregating highly reliable features after the distribution analysis. Secondly, the multiplex-detection cross-attention (MDCA) and multi-head self-attention (MHSA) in MDM cooperate to generate the final representations for the WSI. In this process, the IQ and trainable variational query (VQ) successfully build up the connections between instances and significantly improve the model's robustness toward heterogeneous tumours. At last, to further enforce constraints in the feature space and stabilize the training process, we adopt a memory-based contrastive loss, which is practicable for WSI classification even with a single sample as input in each iteration. We conduct experiments on three computational pathology datasets, e.g., CAMELYON16, TCGA-NSCLC, and TCGA-RCC datasets. The superior accuracy and AUC demonstrate the superiority of our proposed MDMIL over other state-of-the-art methods.

Hongjun Wang, Jiyuan Chen, Tong Pan et al.

Spatial-temporal (ST) graph modeling, such as traffic speed forecasting and taxi demand prediction, is an important task in deep learning area. However, for the nodes in graph, their ST patterns can vary greatly in difficulties for modeling, owning to the heterogeneous nature of ST data. We argue that unveiling the nodes to the model in a meaningful order, from easy to complex, can provide performance improvements over traditional training procedure. The idea has its root in Curriculum Learning which suggests in the early stage of training models can be sensitive to noise and difficult samples. In this paper, we propose ST-Curriculum Dropout, a novel and easy-to-implement strategy for spatial-temporal graph modeling. Specifically, we evaluate the learning difficulty of each node in high-level feature space and drop those difficult ones out to ensure the model only needs to handle fundamental ST relations at the beginning, before gradually moving to hard ones. Our strategy can be applied to any canonical deep learning architecture without extra trainable parameters, and extensive experiments on a wide range of datasets are conducted to illustrate that, by controlling the difficulty level of ST relations as the training progresses, the model is able to capture better representation of the data and thus yields better generalization.

Rong Han, Xiaohong Liu, Tong Pan et al.

Accurately measuring protein-RNA binding affinity is crucial in many biological processes and drug design. Previous computational methods for protein-RNA binding affinity prediction rely on either sequence or structure features, unable to capture the binding mechanisms comprehensively. The recent emerging pre-trained language models trained on massive unsupervised sequences of protein and RNA have shown strong representation ability for various in-domain downstream tasks, including binding site prediction. However, applying different-domain language models collaboratively for complex-level tasks remains unexplored. In this paper, we propose CoPRA to bridge pre-trained language models from different biological domains via Complex structure for Protein-RNA binding Affinity prediction. We demonstrate for the first time that cross-biological modal language models can collaborate to improve binding affinity prediction. We propose a Co-Former to combine the cross-modal sequence and structure information and a bi-scope pre-training strategy for improving Co-Former's interaction understanding. Meanwhile, we build the largest protein-RNA binding affinity dataset PRA310 for performance evaluation. We also test our model on a public dataset for mutation effect prediction. CoPRA reaches state-of-the-art performance on all the datasets. We provide extensive analyses and verify that CoPRA can (1) accurately predict the protein-RNA binding affinity; (2) understand the binding affinity change caused by mutations; and (3) benefit from scaling data and model size.