MaskMol: Knowledge-guided Molecular Image Pre-Training Framework for Activity Cliffs

Zhixiang Cheng; Hongxin Xiang; Pengsen Ma; Li Zeng; Xin Jin; Xixi Yang; Jianxin Lin; Yang Deng; Bosheng Song; Xinxin Feng; Changhui Deng; Xiangxiang Zeng

arXiv · 2409.12926

MaskMol: Knowledge-guided Molecular Image Pre-Training Framework for Activity Cliffs

Zhixiang Cheng·Hongxin Xiang·Pengsen Ma·Li Zeng·Xin Jin·Xixi Yang·Jianxin Lin·Yang Deng·Bosheng Song·Xinxin Feng·Changhui Deng·Xiangxiang Zeng

View original source ↗Read source document ↗Export metadata ↓

Abstract

Activity cliffs, which refer to pairs of molecules that are structurally similar but show significant differences in their potency, can lead to model representation collapse and make the model challenging to distinguish them. Our research indicates that as molecular similarity increases, graph-based methods struggle to capture these nuances, whereas image-based approaches effectively retain the distinctions. Thus, we developed MaskMol, a knowledge-guided molecular image self-supervised learning framework. MaskMol accurately learns the representation of molecular images by considering multiple levels of molecular knowledge, such as atoms, bonds, and substructures. By utilizing pixel masking tasks, MaskMol extracts fine-grained information from molecular images, overcoming the limitations of existing deep learning models in identifying subtle structural changes. Experimental results demonstrate MaskMol's high accuracy and transferability in activity cliff estimation and compound potency prediction across 20 different macromolecular targets, outperforming 25 state-of-the-art deep learning and machine learning approaches. Visualization analyses reveal MaskMol's high biological interpretability in identifying activity cliff-relevant molecular substructures. Notably, through MaskMol, we identified candidate EP4 inhibitors that could be used to treat tumors. This study not only raises awareness about activity cliffs but also introduces a novel method for molecular image representation learning and virtual screening, advancing drug discovery and providing new insights into structure-activity relationships (SAR).

Explore related subjects

cs.CV cs.AI

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Zhixiang Cheng, Hongxin Xiang, Pengsen Ma, Li Zeng, Xin Jin, Xixi Yang, Jianxin Lin, Yang Deng, Bosheng Song, Xinxin Feng, Changhui Deng, Xiangxiang Zeng. 2024-09-02. MaskMol: Knowledge-guided Molecular Image Pre-Training Framework for Activity Cliffs. https://arxiv.org/abs/2409.12926

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

SSP-GNN: Learning to Track via Bilevel Optimization

We propose a graph-based tracking formulation for multi-object tracking (MOT) where target detections contain kinematic information and re-identification features (attributes). Our method applies a successive shortest paths (SSP) algorithm to a tracking graph defined over a batch of frames. The edge costs in this tracking graph are computed via a message-passing network, a graph neural network (GNN) variant. The parameters of the GNN, and hence, the tracker, are learned end-to-end on a training set of example ground-truth tracks and detections. Specifically, learning takes the form of bilevel optimization guided by our novel loss function. We evaluate our algorithm on simulated scenarios to understand its sensitivity to scenario aspects and model hyperparameters. Across varied scenario complexities, our method compares favorably to a strong baseline.

cs.CV↗

arXiv2026

AdaptiveCDM: Source-Free Few-Shot Domain Adaptation for Cell Detection in Microscopic Images

Cross-domain cell detection for microscopic images suffers from performance degradation due to distribution shifts across imaging domains. Unsupervised Domain Adaptation (UDA) strategies, attempt to overcome domain sift without requiring annotated data from target. However, requirement of availability of annotated data from the source domain and large-size data from target domain are both challenging limitations for realistic scenarios. This is especially true in medical imaging, where privacy requirements might prevent access to annotated source data, and costly data acquisition restricts extensive sampling of the target domain. To address these challenges, we propose AdaptiveCDM, a modular framework for Source-Free Few-Shot Domain Adaptive Object Detection (SF-FSDAOD) setting, that adapts a pretrained source model using only few labeled target images without accessing source data. AdaptiveCDM combines Resolution-Aware Augmentation (RAug) and Category-Aware Representation Learning (CARL). RAug alleviates the scarcity and class imbalance by augmenting instance balanced training examples, while preserving the scale fidelity and morphological properties of cellular structures. CARL enhances discriminative representation learning by encouraging class-consistent proposals, improving both localization and classification. We also introduce two competitive baselines for proposed setting: Faster-FreeShot and MT-FreeShot. Our approach achieves 40.4/43.4 mAP0.5 on M5 and 67.1/75.5 mAP0.5 on Raabin-WBC under 2-/5-shot adaptation. Despite using only a few labeled target images and no source data, AdaptiveCDM achieves competitive or superior performance compared with SOTA methods under their respective supervision settings. Ablations and qualitative analyses further substantiate the contribution of each component and the effectiveness of AdaptiveCDM in low-data regimes. Code/models will be available.

cs.CV↗

arXiv2026

Uncertainty-Weighted Fusion of Image and Synthetic Event for Video Anomaly Detection

Most existing video anomaly detectors rely on RGB frames alone, which limit their ability to capture abrupt or transient motion cues that are critical for identifying anomalous events. We propose Uncertainty Weighted Image Event Fusion (IEF-VAD), a framework that integrates complementary RGB and synthetic motion information through a principled weighting mechanism. The method models the high variance and heavy tailed characteristics of synthetic motion cues with a Student's t likelihood, computes value level inverse variance weights using a Laplace approximation to prevent the image modality from overshadowing motion information, and performs iterative refinement to suppress residual cross modal noise. This formulation provides a more balanced and reliable fusion process compared to cross attention or gating based approaches that often suffer from modality dominance. Without requiring an event camera or frame level annotations, IEF-VAD achieves new state of the art performance on multiple real world anomaly detection benchmarks and remains stable under degradation applied to individual modalities. The results indicate that extracting and integrating complementary motion cues is an effective direction for robust video understanding across diverse environments.

cs.CV↗