Accurate cross-modality cardiac image segmentation is essential for effectively diagnosing and treating heart disease. Different imaging modalities help to determine suitable pre-procedure planning. However, most methods face the difficulty of spatial-temporal confounding, where the anatomy element and modality element of cardiac images are intertwined across both spatial and temporal dimensions. It is derived from the imaging diversity and structure diversity of cardiac images. The spatial-temporal confounding hinders knowledge transfer between cardiac images on different modalities. In this paper, we propose a novel dynamic causal learning (DCL) to solve spatial-temporal confounding. The DCL explores multi-dimensional causal intervention to consider not only the causal relationship between images and labels, but also the causality in time dimension and space dimension. It integrates historical optimal interventions and facilitates the transfer of this knowledge across temporal contexts. In addition, the DCL utilizes the diffusion mechanism to further ensure that the extracted anatomy element remains causal invariant, improving model performance across multiple imaging modalities. Extensive experiments on cross-modality cardiac images (MR, CT, and US) demonstrate the effectiveness of the DCL (mean Dice = 0.951), outperforming other advanced segmentation methods. DCL is freely accessible at https://github.com/asdww0721ww/DCL.

Echocardiography video segmentation is critical for cardiovascular disease diagnosis. However, it still suffers from the challenge of dual-level bias. This challenge derives from the frame-level bias in temporal dimension and the object-level bias in the spatial dimension on echocardiography video. To overcome this challenge, we propose a spatial-temporal consistency (STC) model based on semi-supervised learning for echocardiography video segmentation. This model aligns and fuses inter-frame and inter-object context-aware feature representations. First, the STC explores a temporal context-aware (TCA) module to focus on motion differences between frames. This module extracts temporal correlation through inter-frame attention to compensate for important temporal semantic information. Second, the STC proposes a multi-object semantic adaptation (MSA) module that not only adaptively calibrates frame-level feature and object-level feature, but also fuses these features at different layers. Finally, the STC considers spatial-temporal consistency constraint to reduce prediction error among multiple MSA modules, thereby achieving low-entropy prediction. Extensive experiments demonstrate that the STC achieves state-of-the-art performance for echocardiography video segmentation.

Predicting the pharmacological activity, toxicity, and pharmacokinetic properties of molecules is a central task in drug discovery. Existing machine learning methods are transferred from one resource rich molecular property to another data scarce property in the same scaffold dataset. However, existing models may produce fragile and highly uncertain predictions for new scaffold molecules. And these models were tested on different benchmarks, which seriously affected the quality of their evaluation results. In this article, we introduce Meta-MolNet, a collection of data benchmark and algorithms, which is a standard benchmark platform for measuring model generalization and uncertainty quantification capabilities. Meta-MolNet manages a wide range of molecular datasets with high ratio of molecules/scaffolds, which often leads to more difficult data shift and generalization problems. Furthermore, we propose a graph attention network based on cross-domain meta-learning, Meta-GAT, which uses bilevel optimization to learn meta-knowledge from the scaffold family molecular dataset in the source domain. Meta-GAT benefits from meta-knowledge that reduces the requirement of sample complexity to enable reliable predictions of new scaffold molecules in the target domain through internal iteration of a few examples. We evaluate existing methods as baselines for the community, and the Meta-MolNet benchmark demonstrates the effectiveness of measuring the proposed algorithm in domain generalization and uncertainty quantification. Extensive experiments demonstrate that the Meta-GAT model has state-of-the-art domain generalization performance and robustly estimates uncertainty under few examples constraints. By publishing AI-ready data, evaluation frameworks, and baseline results, we hope to see the Meta-MolNet suite become a comprehensive resource for the AI-assisted drug discovery community. Meta-MolNet is freely accessible at https://github.com/lol88/Meta-MolNet.

While computer vision has proven valuable for medical image segmentation, its application faces challenges such as limited dataset sizes and the complexity of effectively leveraging unlabeled images. To address these challenges, we present a novel semi-supervised, consistency-based approach termed the data-efficient medical segmenter (DEMS). The DEMS features an encoder-decoder architecture and incorporates the developed online automatic augmenter (OAA) and residual robustness enhancement (RRE) blocks. The OAA augments input data with various image transformations, thereby diversifying the dataset to improve the generalization ability. The RRE enriches feature diversity and introduces perturbations to create varied inputs for different decoders, thereby providing enhanced variability. Moreover, we introduce a sensitive loss to further enhance consistency across different decoders and stabilize the training process. Extensive experimental results on both our own and three public datasets affirm the effectiveness of DEMS. Under extreme data shortage scenarios, our DEMS achieves 16.85% and 10.37% improvement in dice score compared with the U-Net and top-performed state-of-the-art method, respectively. Given its superior data efficiency, DEMS could present significant advancements in medical segmentation under small data regimes. The project homepage can be accessed at https://github.com/NUS-Tim/DEMS.

Inductive bias in machine learning (ML) is the set of assumptions describing how a model makes predictions. Different ML-based methods for protein-ligand binding affinity (PLA) prediction have different inductive biases, leading to different levels of generalization capability and interpretability. Intuitively, the inductive bias of an ML-based model for PLA prediction should fit in with biological mechanisms relevant for binding to achieve good predictions with meaningful reasons. To this end, we propose an interaction-based inductive bias to restrict neural networks to functions relevant for binding with two assumptions: 1) A protein-ligand complex can be naturally expressed as a heterogeneous graph with covalent and non-covalent interactions; 2) The predicted PLA is the sum of pairwise atom-atom affinities determined by non-covalent interactions. The interaction-based inductive bias is embodied by an explainable heterogeneous interaction graph neural network (EHIGN) for explicitly modeling pairwise atom-atom interactions to predict PLA from 3D structures. Extensive experiments demonstrate that EHIGN achieves better generalization capability than other state-of-the-art ML-based baselines in PLA prediction and structure-based virtual screening. More importantly, comprehensive analyses of distance-affinity, pose-affinity, and substructure-affinity relations suggest that the interaction-based inductive bias can guide the model to learn atomic interactions that are consistent with physical reality. As a case study to demonstrate practical usefulness, our method is tested for predicting the efficacy of Nirmatrelvir against SARS-CoV-2 variants. EHIGN successfully recognizes the changes in the efficacy of Nirmatrelvir for different SARS-CoV-2 variants with meaningful reasons.

Finding candidate molecules with favorable pharmacological activity, low toxicity, and proper pharmacokinetic properties is an important task in drug discovery. Deep neural networks have made impressive progress in accelerating and improving drug discovery. However, these techniques rely on a large amount of label data to form accurate predictions of molecular properties. At each stage of the drug discovery pipeline, usually, only a few biological data of candidate molecules and derivatives are available, indicating that the application of deep neural networks for low-data drug discovery is still a formidable challenge. Here, we propose a meta learning architecture with graph attention network, Meta-GAT, to predict molecular properties in low-data drug discovery. The GAT captures the local effects of atomic groups at the atom level through the triple attentional mechanism and implicitly captures the interactions between different atomic groups at the molecular level. GAT is used to perceive molecular chemical environment and connectivity, thereby effectively reducing sample complexity. Meta-GAT further develops a meta learning strategy based on bilevel optimization, which transfers meta knowledge from other attribute prediction tasks to low-data target tasks. In summary, our work demonstrates how meta learning can reduce the amount of data required to make meaningful predictions of molecules in low-data scenarios. Meta learning is likely to become the new learning paradigm in low-data drug discovery. The source code is publicly available at: https://github.com/lol88/Meta-GAT.

With the rapid development of proteomics and the rapid increase of target molecules for drug action, computer-aided drug design (CADD) has become a basic task in drug discovery. One of the key challenges in CADD is molecular representation. High-quality molecular expression with chemical intuition helps to promote many boundary problems of drug discovery. At present, molecular representation still faces several urgent problems, such as the polysemy of substructures and unsmooth information flow between atomic groups. In this research, we propose a deep contextualized Bi-LSTM architecture, Mol2Context-vec, which can integrate different levels of internal states to bring dynamic representations of molecular substructures. And the obtained molecular context representation can capture the interactions between any atomic groups, especially a pair of atomic groups that are topologically distant. Experiments show that Mol2Context-vec achieves state-of-the-art performance on multiple benchmark datasets. In addition, the visual interpretation of Mol2Context-vec is very close to the structural properties of chemical molecules as understood by humans. These advantages indicate that Mol2Context-vec can be used as a reliable and effective tool for molecular expression. Availability: The source code is available for download in https://github.com/lol88/Mol2Context-vec.