In recent years, self-supervised learning has emerged as a powerful tool to harness abundant unlabelled data for representation learning and has been broadly adopted in diverse areas. However, when applied to molecular representation learning (MRL), prevailing techniques such as masked sub-unit reconstruction often fall short, due to the high degree of freedom in the possible combinations of atoms within molecules, which brings insurmountable complexity to the masking-reconstruction paradigm. To tackle this challenge, we introduce REMO, a self-supervised learning framework that takes advantage of well-defined atom-combination rules in common chemistry. Specifically, REMO pre-trains graph/Transformer encoders on 1.7 million known chemical reactions in the literature. We propose two pre-training objectives: Masked Reaction Centre Reconstruction (MRCR) and Reaction Centre Identification (RCI). REMO offers a novel solution to MRL by exploiting the underlying shared patterns in chemical reactions as \textit{context} for pre-training, which effectively infers meaningful representations of common chemistry knowledge. Such contextual representations can then be utilized to support diverse downstream molecular tasks with minimum finetuning, such as affinity prediction and drug-drug interaction prediction. Extensive experimental results on MoleculeACE, ACNet, drug-drug interaction (DDI), and reaction type classification show that across all tested downstream tasks, REMO outperforms the standard baseline of single-molecule masked modeling used in current MRL. Remarkably, REMO is the pioneering deep learning model surpassing fingerprint-based methods in activity cliff benchmarks.
The generation of 3D molecules requires simultaneously deciding the categorical features~(atom types) and continuous features~(atom coordinates). Deep generative models, especially Diffusion Models (DMs), have demonstrated effectiveness in generating feature-rich geometries. However, existing DMs typically suffer from unstable probability dynamics with inefficient sampling speed. In this paper, we introduce geometric flow matching, which enjoys the advantages of both equivariant modeling and stabilized probability dynamics. More specifically, we propose a hybrid probability path where the coordinates probability path is regularized by an equivariant optimal transport, and the information between different modalities is aligned. Experimentally, the proposed method could consistently achieve better performance on multiple molecule generation benchmarks with 4.75$\times$ speed up of sampling on average.
While molecular pre-training has shown great potential in enhancing drug discovery, the lack of a solid physical interpretation in current methods raises concerns about whether the learned representation truly captures the underlying explanatory factors in observed data, ultimately resulting in limited generalization and robustness. Although denoising methods offer a physical interpretation, their accuracy is often compromised by ad-hoc noise design, leading to inaccurate learned force fields. To address this limitation, this paper proposes a new method for molecular pre-training, called sliced denoising (SliDe), which is based on the classical mechanical intramolecular potential theory. SliDe utilizes a novel noise strategy that perturbs bond lengths, angles, and torsion angles to achieve better sampling over conformations. Additionally, it introduces a random slicing approach that circumvents the computationally expensive calculation of the Jacobian matrix, which is otherwise essential for estimating the force field. By aligning with physical principles, SliDe shows a 42\% improvement in the accuracy of estimated force fields compared to current state-of-the-art denoising methods, and thus outperforms traditional baselines on various molecular property prediction tasks.
Coordinate denoising is a promising 3D molecular pre-training method, which has achieved remarkable performance in various downstream drug discovery tasks. Theoretically, the objective is equivalent to learning the force field, which is revealed helpful for downstream tasks. Nevertheless, there are two challenges for coordinate denoising to learn an effective force field, i.e. low coverage samples and isotropic force field. The underlying reason is that molecular distributions assumed by existing denoising methods fail to capture the anisotropic characteristic of molecules. To tackle these challenges, we propose a novel hybrid noise strategy, including noises on both dihedral angel and coordinate. However, denoising such hybrid noise in a traditional way is no more equivalent to learning the force field. Through theoretical deductions, we find that the problem is caused by the dependency of the input conformation for covariance. To this end, we propose to decouple the two types of noise and design a novel fractional denoising method (Frad), which only denoises the latter coordinate part. In this way, Frad enjoys both the merits of sampling more low-energy structures and the force field equivalence. Extensive experiments show the effectiveness of Frad in molecular representation, with a new state-of-the-art on 9 out of 12 tasks of QM9 and on 7 out of 8 targets of MD17.
This paper introduces the Attribute-Decomposed GAN, a novel generative model for controllable person image synthesis, which can produce realistic person images with desired human attributes (e.g., pose, head, upper clothes and pants) provided in various source inputs. The core idea of the proposed model is to embed human attributes into the latent space as independent codes and thus achieve flexible and continuous control of attributes via mixing and interpolation operations in explicit style representations. Specifically, a new architecture consisting of two encoding pathways with style block connections is proposed to decompose the original hard mapping into multiple more accessible subtasks. In source pathway, we further extract component layouts with an off-the-shelf human parser and feed them into a shared global texture encoder for decomposed latent codes. This strategy allows for the synthesis of more realistic output images and automatic separation of un-annotated attributes. Experimental results demonstrate the proposed method's superiority over the state of the art in pose transfer and its effectiveness in the brand-new task of component attribute transfer.
Convolutional neural networks require numerous data for training. Considering the difficulties in data collection and labeling in some specific tasks, existing approaches generally use models pre-trained on a large source domain (e.g. ImageNet), and then fine-tune them on these tasks. However, the datasets from source domain are simply discarded in the fine-tuning process. We argue that the source datasets could be better utilized and benefit fine-tuning. This paper firstly introduces the concept of general discrimination to describe ability of a network to distinguish untrained patterns, and then experimentally demonstrates that general discrimination could potentially enhance the total discrimination ability on target domain. Furthermore, we propose a novel and light-weighted method, namely soft fine-tuning. Unlike traditional fine-tuning which directly replaces optimization objective by a loss function on the target domain, soft fine-tuning effectively keeps general discrimination by holding the previous loss and removes it softly. By doing so, soft fine-tuning improves the robustness of the network to data bias, and meanwhile accelerates the convergence. We evaluate our approach on several visual recognition tasks. Extensive experimental results support that soft fine-tuning provides consistent improvement on all evaluated tasks, and outperforms the state-of-the-art significantly. Codes will be made available to the public.
We propose Unified Visual-Semantic Embeddings (UniVSE) for learning a joint space of visual and textual concepts. The space unifies the concepts at different levels, including objects, attributes, relations, and full scenes. A contrastive learning approach is proposed for the fine-grained alignment from only image-caption pairs. Moreover, we present an effective approach for enforcing the coverage of semantic components that appear in the sentence. We demonstrate the robustness of Unified VSE in defending text-domain adversarial attacks on cross-modal retrieval tasks. Such robustness also empowers the use of visual cues to resolve word dependencies in novel sentences.
We propose the Unified Visual-Semantic Embeddings (Unified VSE) for learning a joint space of visual representation and textual semantics. The model unifies the embeddings of concepts at different levels: objects, attributes, relations, and full scenes. We view the sentential semantics as a combination of different semantic components such as objects and relations; their embeddings are aligned with different image regions. A contrastive learning approach is proposed for the effective learning of this fine-grained alignment from only image-caption pairs. We also present a simple yet effective approach that enforces the coverage of caption embeddings on the semantic components that appear in the sentence. We demonstrate that the Unified VSE outperforms baselines on cross-modal retrieval tasks; the enforcement of the semantic coverage improves the model's robustness in defending text-domain adversarial attacks. Moreover, our model empowers the use of visual cues to accurately resolve word dependencies in novel sentences.
Large scale image dataset and deep convolutional neural network (DCNN) are two primary driving forces for the rapid progress made in generic object recognition tasks in recent years. While lots of network architectures have been continuously designed to pursue lower error rates, few efforts are devoted to enlarge existing datasets due to high labeling cost and unfair comparison issues. In this paper, we aim to achieve lower error rate by augmenting existing datasets in an automatic manner. Our method leverages both Web and DCNN, where Web provides massive images with rich contextual information, and DCNN replaces human to automatically label images under guidance of Web contextual information. Experiments show our method can automatically scale up existing datasets significantly from billions web pages with high accuracy, and significantly improve the performance on object recognition tasks by using the automatically augmented datasets, which demonstrates that more supervisory information has been automatically gathered from the Web. Both the dataset and models trained on the dataset are made publicly available.