InstructBio: A Large-scale Semi-supervised Learning Paradigm for Biochemical Problems

In the field of artificial intelligence for science, it is consistently an essential challenge to face a limited amount of labeled data for real-world problems. The prevailing approach is to pretrain a powerful task-agnostic model on a large unlabeled corpus but may struggle to transfer knowledge to downstream tasks. In this study, we propose InstructMol, a semi-supervised learning algorithm, to take better advantage of unlabeled examples. It introduces an instructor model to provide the confidence ratios as the measurement of pseudo-labels' reliability. These confidence scores then guide the target model to pay distinct attention to different data points, avoiding the over-reliance on labeled data and the negative influence of incorrect pseudo-annotations. Comprehensive experiments show that InstructBio substantially improves the generalization ability of molecular models, in not only molecular property predictions but also activity cliff estimations, demonstrating the superiority of the proposed method. Furthermore, our evidence indicates that InstructBio can be equipped with cutting-edge pretraining methods and used to establish large-scale and task-specific pseudo-labeled molecular datasets, which reduces the predictive errors and shortens the training process. Our work provides strong evidence that semi-supervised learning can be a promising tool to overcome the data scarcity limitation and advance molecular representation learning.

Towards Reasonable Budget Allocation in Untargeted Graph Structure Attacks via Gradient Debias

It has become cognitive inertia to employ cross-entropy loss function in classification related tasks. In the untargeted attacks on graph structure, the gradients derived from the attack objective are the attacker's basis for evaluating a perturbation scheme. Previous methods use negative cross-entropy loss as the attack objective in attacking node-level classification models. However, the suitability of the cross-entropy function for constructing the untargeted attack objective has yet been discussed in previous works. This paper argues about the previous unreasonable attack objective from the perspective of budget allocation. We demonstrate theoretically and empirically that negative cross-entropy tends to produce more significant gradients from nodes with lower confidence in the labeled classes, even if the predicted classes of these nodes have been misled. To free up these inefficient attack budgets, we propose a simple attack model for untargeted attacks on graph structure based on a novel attack objective which generates unweighted gradients on graph structures that are not affected by the node confidence. By conducting experiments in gray-box poisoning attack scenarios, we demonstrate that a reasonable budget allocation can significantly improve the effectiveness of gradient-based edge perturbations without any extra hyper-parameter.

CVT-SLR: Contrastive Visual-Textual Transformation for Sign Language Recognition with Variational Alignment

Sign language recognition (SLR) is a weakly supervised task that annotates sign videos as textual glosses. Recent studies show that insufficient training caused by the lack of large-scale available sign datasets becomes the main bottleneck for SLR. Most SLR works thereby adopt pretrained visual modules and develop two mainstream solutions. The multi-stream architectures extend multi-cue visual features, yielding the current SOTA performances but requiring complex designs and might introduce potential noise. Alternatively, the advanced single-cue SLR frameworks using explicit cross-modal alignment between visual and textual modalities are simple and effective, potentially competitive with the multi-cue framework. In this work, we propose a novel contrastive visual-textual transformation for SLR, CVT-SLR, to fully explore the pretrained knowledge of both the visual and language modalities. Based on the single-cue cross-modal alignment framework, we propose a variational autoencoder (VAE) for pretrained contextual knowledge while introducing the complete pretrained language module. The VAE implicitly aligns visual and textual modalities while benefiting from pretrained contextual knowledge as the traditional contextual module. Meanwhile, a contrastive cross-modal alignment algorithm is designed to explicitly enhance the consistency constraints. Extensive experiments on public datasets (PHOENIX-2014 and PHOENIX-2014T) demonstrate that our proposed CVT-SLR consistently outperforms existing single-cue methods and even outperforms SOTA multi-cue methods.

Lightweight Contrastive Protein Structure-Sequence Transformation

Pretrained protein structure models without labels are crucial foundations for the majority of protein downstream applications. The conventional structure pretraining methods follow the mature natural language pretraining methods such as denoised reconstruction and masked language modeling but usually destroy the real representation of spatial structures. The other common pretraining methods might predict a fixed set of predetermined object categories, where a restricted supervised manner limits their generality and usability as additional labeled data is required to specify any other protein concepts. In this work, we introduce a novel unsupervised protein structure representation pretraining with a robust protein language model. In particular, we first propose to leverage an existing pretrained language model to guide structure model learning through an unsupervised contrastive alignment. In addition, a self-supervised structure constraint is proposed to further learn the intrinsic information about the structures. With only light training data, the pretrained structure model can obtain better generalization ability. To quantitatively evaluate the proposed structure models, we design a series of rational evaluation methods, including internal tasks (e.g., contact map prediction, distribution alignment quality) and external/downstream tasks (e.g., protein design). The extensive experimental results conducted on multiple tasks and specific datasets demonstrate the superiority of the proposed sequence-structure transformation framework.

PrefixMol: Target- and Chemistry-aware Molecule Design via Prefix Embedding

Is there a unified model for generating molecules considering different conditions, such as binding pockets and chemical properties? Although target-aware generative models have made significant advances in drug design, they do not consider chemistry conditions and cannot guarantee the desired chemical properties. Unfortunately, merging the target-aware and chemical-aware models into a unified model to meet customized requirements may lead to the problem of negative transfer. Inspired by the success of multi-task learning in the NLP area, we use prefix embeddings to provide a novel generative model that considers both the targeted pocket's circumstances and a variety of chemical properties. All conditional information is represented as learnable features, which the generative model subsequently employs as a contextual prompt. Experiments show that our model exhibits good controllability in both single and multi-conditional molecular generation. The controllability enables us to outperform previous structure-based drug design methods. More interestingly, we open up the attention mechanism and reveal coupling relationships between conditions, providing guidance for multi-conditional molecule generation.

Improving (Dis)agreement Detection with Inductive Social Relation Information From Comment-Reply Interactions

(Dis)agreement detection aims to identify the authors' attitudes or positions (\textit{{agree, disagree, neutral}}) towards a specific text. It is limited for existing methods merely using textual information for identifying (dis)agreements, especially for cross-domain settings. Social relation information can play an assistant role in the (dis)agreement task besides textual information. We propose a novel method to extract such relation information from (dis)agreement data into an inductive social relation graph, merely using the comment-reply pairs without any additional platform-specific information. The inductive social relation globally considers the historical discussion and the relation between authors. Textual information based on a pre-trained language model and social relation information encoded by pre-trained RGCN are jointly considered for (dis)agreement detection. Experimental results show that our model achieves state-of-the-art performance for both the in-domain and cross-domain tasks on the benchmark -- DEBAGREEMENT. We find social relations can boost the performance of the (dis)agreement detection model, especially for the long-token comment-reply pairs, demonstrating the effectiveness of the social relation graph. We also explore the effect of the knowledge graph embedding methods, the information fusing method, and the time interval in constructing the social relation graph, which shows the effectiveness of our model.

Data-Efficient Protein 3D Geometric Pretraining via Refinement of Diffused Protein Structure Decoy

Learning meaningful protein representation is important for a variety of biological downstream tasks such as structure-based drug design. Having witnessed the success of protein sequence pretraining, pretraining for structural data which is more informative has become a promising research topic. However, there are three major challenges facing protein structure pretraining: insufficient sample diversity, physically unrealistic modeling, and the lack of protein-specific pretext tasks. To try to address these challenges, we present the 3D Geometric Pretraining. In this paper, we propose a unified framework for protein pretraining and a 3D geometric-based, data-efficient, and protein-specific pretext task: RefineDiff (Refine the Diffused Protein Structure Decoy). After pretraining our geometric-aware model with this task on limited data(less than 1% of SOTA models), we obtained informative protein representations that can achieve comparable performance for various downstream tasks.

Characterization and Generation of 3D Realistic Geological Particles with Metaball Descriptor based on X-Ray Computed Tomography

The morphology of geological particles is crucial in determining its granular characteristics and assembly responses. In this paper, Metaball-function based solutions are proposed for morphological characterization and generation of three-dimensional realistic particles according to the X-ray Computed Tomography (XRCT) images. For characterization, we develop a geometric-based Metaball-Imaging algorithm. This algorithm can capture the main contour of parental particles with a series of non-overlapping spheres and refine surface-texture details through gradient search. Four types of particles, hundreds of samples, are applied for evaluations. The result shows good matches on key morphological indicators(i.e., volume, surface area, sphericity, circularity, corey-shape factor, nominal diameter and surface-equivalent-sphere diameter), confirming its characterization precision. For generation, we propose the Metaball Variational Autoencoder. Assisted by deep neural networks, this method can generate 3D particles in Metaball form, while retaining coessential morphological features with parental particles. Additionally, this method allows for control over the generated shapes through an arithmetic pattern, enabling the generation of particles with specific shapes. Two sets of XRCT images different in sample number and geometric features are chosen as parental data. On each training set, one thousand particles are generated for validations. The generation fidelity is demonstrated through comparisons of morphologies and shape-feature distributions between generated and parental particles. Examples are also provided to demonstrate controllability on the generated shapes. With Metaball-based simulations frameworks previously proposed by the authors, these methods have the potential to provide valuable insights into the properties and behavior of actual geological particles.