Protein-Ligand Complex Generator & Drug Screening via Tiered Tensor Transform

Accurate determination of a small molecule candidate (ligand) binding pose in its target protein pocket is important for computer-aided drug discovery. Typical rigid-body docking methods ignore the pocket flexibility of protein, while the more accurate pose generation using molecular dynamics is hindered by slow protein dynamics. We develop a tiered tensor transform (3T) algorithm to rapidly generate diverse protein-ligand complex conformations for both pose and affinity estimation in drug screening, requiring neither machine learning training nor lengthy dynamics computation, while maintaining both coarse-grain-like coordinated protein dynamics and atomistic-level details of the complex pocket. The 3T conformation structures we generate are closer to experimental co-crystal structures than those generated by docking software, and more importantly achieve significantly higher accuracy in active ligand classification than traditional ensemble docking using hundreds of experimental protein conformations. 3T structure transformation is decoupled from the system physics, making future usage in other computational scientific domains possible.

Personalizing Intervened Network for Long-tailed Sequential User Behavior Modeling

In an era of information explosion, recommendation systems play an important role in people's daily life by facilitating content exploration. It is known that user activeness, i.e., number of behaviors, tends to follow a long-tail distribution, where the majority of users are with low activeness. In practice, we observe that tail users suffer from significantly lower-quality recommendation than the head users after joint training. We further identify that a model trained on tail users separately still achieve inferior results due to limited data. Though long-tail distributions are ubiquitous in recommendation systems, improving the recommendation performance on the tail users still remains challenge in both research and industry. Directly applying related methods on long-tail distribution might be at risk of hurting the experience of head users, which is less affordable since a small portion of head users with high activeness contribute a considerate portion of platform revenue. In this paper, we propose a novel approach that significantly improves the recommendation performance of the tail users while achieving at least comparable performance for the head users over the base model. The essence of this approach is a novel Gradient Aggregation technique that learns common knowledge shared by all users into a backbone model, followed by separate plugin prediction networks for the head users and the tail users personalization. As for common knowledge learning, we leverage the backward adjustment from the causality theory for deconfounding the gradient estimation and thus shielding off the backbone training from the confounder, i.e., user activeness. We conduct extensive experiments on two public recommendation benchmark datasets and a large-scale industrial datasets collected from the Alipay platform. Empirical studies validate the rationality and effectiveness of our approach.

CCL4Rec: Contrast over Contrastive Learning for Micro-video Recommendation

Micro-video recommender systems suffer from the ubiquitous noises in users' behaviors, which might render the learned user representation indiscriminating, and lead to trivial recommendations (e.g., popular items) or even weird ones that are far beyond users' interests. Contrastive learning is an emergent technique for learning discriminating representations with random data augmentations. However, due to neglecting the noises in user behaviors and treating all augmented samples equally, the existing contrastive learning framework is insufficient for learning discriminating user representations in recommendation. To bridge this research gap, we propose the Contrast over Contrastive Learning framework for training recommender models, named CCL4Rec, which models the nuances of different augmented views by further contrasting augmented positives/negatives with adaptive pulling/pushing strengths, i.e., the contrast over (vanilla) contrastive learning. To accommodate these contrasts, we devise the hardness-aware augmentations that track the importance of behaviors being replaced in the query user and the relatedness of substitutes, and thus determining the quality of augmented positives/negatives. The hardness-aware augmentation also permits controllable contrastive learning, leading to performance gains and robust training. In this way, CCL4Rec captures the nuances of historical behaviors for a given user, which explicitly shields off the learned user representation from the effects of noisy behaviors. We conduct extensive experiments on two micro-video recommendation benchmarks, which demonstrate that CCL4Rec with far less model parameters could achieve comparable performance to existing state-of-the-art method, and improve the training/inference speed by several orders of magnitude.

Re4: Learning to Re-contrast, Re-attend, Re-construct for Multi-interest Recommendation

Effectively representing users lie at the core of modern recommender systems. Since users' interests naturally exhibit multiple aspects, it is of increasing interest to develop multi-interest frameworks for recommendation, rather than represent each user with an overall embedding. Despite their effectiveness, existing methods solely exploit the encoder (the forward flow) to represent multiple aspects of interests. However, without explicit regularization, the interest embeddings may not be distinct from each other nor semantically reflect representative historical items. Towards this end, we propose the Re4 framework, which leverages the backward flow to reexamine each interest embedding. Specifically, Re4 encapsulates three backward flows, i.e., 1) Re-contrast, which drives each interest embedding to be distinct from other interests using contrastive learning; 2) Re-attend, which ensures the interest-item correlation estimation in the forward flow to be consistent with the criterion used in final recommendation; and 3) Re-construct, which ensures that each interest embedding can semantically reflect the information of representative items that relate to the corresponding interest. We demonstrate the novel forward-backward multi-interest paradigm on ComiRec, and perform extensive experiments on three real-world datasets. Empirical studies validate that Re4 helps to learn learning distinct and effective multi-interest representations.

Dilated Context Integrated Network with Cross-Modal Consensus for Temporal Emotion Localization in Videos

Understanding human emotions is a crucial ability for intelligent robots to provide better human-robot interactions. The existing works are limited to trimmed video-level emotion classification, failing to locate the temporal window corresponding to the emotion. In this paper, we introduce a new task, named Temporal Emotion Localization in videos~(TEL), which aims to detect human emotions and localize their corresponding temporal boundaries in untrimmed videos with aligned subtitles. TEL presents three unique challenges compared to temporal action localization: 1) The emotions have extremely varied temporal dynamics; 2) The emotion cues are embedded in both appearances and complex plots; 3) The fine-grained temporal annotations are complicated and labor-intensive. To address the first two challenges, we propose a novel dilated context integrated network with a coarse-fine two-stream architecture. The coarse stream captures varied temporal dynamics by modeling multi-granularity temporal contexts. The fine stream achieves complex plots understanding by reasoning the dependency between the multi-granularity temporal contexts from the coarse stream and adaptively integrates them into fine-grained video segment features. To address the third challenge, we introduce a cross-modal consensus learning paradigm, which leverages the inherent semantic consensus between the aligned video and subtitle to achieve weakly-supervised learning. We contribute a new testing set with 3,000 manually-annotated temporal boundaries so that future research on the TEL problem can be quantitatively evaluated. Extensive experiments show the effectiveness of our approach on temporal emotion localization. The repository of this work is at https://github.com/YYJMJC/Temporal-Emotion-Localization-in-Videos.

BOSS: Bottom-up Cross-modal Semantic Composition with Hybrid Counterfactual Training for Robust Content-based Image Retrieval

Content-Based Image Retrieval (CIR) aims to search for a target image by concurrently comprehending the composition of an example image and a complementary text, which potentially impacts a wide variety of real-world applications, such as internet search and fashion retrieval. In this scenario, the input image serves as an intuitive context and background for the search, while the corresponding language expressly requests new traits on how specific characteristics of the query image should be modified in order to get the intended target image. This task is challenging since it necessitates learning and understanding the composite image-text representation by incorporating cross-granular semantic updates. In this paper, we tackle this task by a novel \underline{\textbf{B}}ottom-up cr\underline{\textbf{O}}ss-modal \underline{\textbf{S}}emantic compo\underline{\textbf{S}}ition (\textbf{BOSS}) with Hybrid Counterfactual Training framework, which sheds new light on the CIR task by studying it from two previously overlooked perspectives: \emph{implicitly bottom-up composition of visiolinguistic representation} and \emph{explicitly fine-grained correspondence of query-target construction}. On the one hand, we leverage the implicit interaction and composition of cross-modal embeddings from the bottom local characteristics to the top global semantics, preserving and transforming the visual representation conditioned on language semantics in several continuous steps for effective target image search. On the other hand, we devise a hybrid counterfactual training strategy that can reduce the model's ambiguity for similar queries.

Intelligent Request Strategy Design in Recommender System

Waterfall Recommender System (RS), a popular form of RS in mobile applications, is a stream of recommended items consisting of successive pages that can be browsed by scrolling. In waterfall RS, when a user finishes browsing a page, the edge (e.g., mobile phones) would send a request to the cloud server to get a new page of recommendations, known as the paging request mechanism. RSs typically put a large number of items into one page to reduce excessive resource consumption from numerous paging requests, which, however, would diminish the RSs' ability to timely renew the recommendations according to users' real-time interest and lead to a poor user experience. Intuitively, inserting additional requests inside pages to update the recommendations with a higher frequency can alleviate the problem. However, previous attempts, including only non-adaptive strategies (e.g., insert requests uniformly), would eventually lead to resource overconsumption. To this end, we envision a new learning task of edge intelligence named Intelligent Request Strategy Design (IRSD). It aims to improve the effectiveness of waterfall RSs by determining the appropriate occasions of request insertion based on users' real-time intention. Moreover, we propose a new paradigm of adaptive request insertion strategy named Uplift-based On-edge Smart Request Framework (AdaRequest). AdaRequest 1) captures the dynamic change of users' intentions by matching their real-time behaviors with their historical interests based on attention-based neural networks. 2) estimates the counterfactual uplift of user purchase brought by an inserted request based on causal inference. 3) determines the final request insertion strategy by maximizing the utility function under online resource constraints. We conduct extensive experiments on both offline dataset and online A/B test to verify the effectiveness of AdaRequest.

ODBO: Bayesian Optimization with Search Space Prescreening for Directed Protein Evolution

Directed evolution is a versatile technique in protein engineering that mimics the process of natural selection by iteratively alternating between mutagenesis and screening in order to search for sequences that optimize a given property of interest, such as catalytic activity and binding affinity to a specified target. However, the space of possible proteins is too large to search exhaustively in the laboratory, and functional proteins are scarce in the vast sequence space. Machine learning (ML) approaches can accelerate directed evolution by learning to map protein sequences to functions without building a detailed model of the underlying physics, chemistry and biological pathways. Despite the great potentials held by these ML methods, they encounter severe challenges in identifying the most suitable sequences for a targeted function. These failures can be attributed to the common practice of adopting a high-dimensional feature representation for protein sequences and inefficient search methods. To address these issues, we propose an efficient, experimental design-oriented closed-loop optimization framework for protein directed evolution, termed ODBO, which employs a combination of novel low-dimensional protein encoding strategy and Bayesian optimization enhanced with search space prescreening via outlier detection. We further design an initial sample selection strategy to minimize the number of experimental samples for training ML models. We conduct and report four protein directed evolution experiments that substantiate the capability of the proposed framework for finding of the variants with properties of interest. We expect the ODBO framework to greatly reduce the experimental cost and time cost of directed evolution, and can be further generalized as a powerful tool for adaptive experimental design in a broader context.

Contrastive Learning with Positive-Negative Frame Mask for Music Representation

Self-supervised learning, especially contrastive learning, has made an outstanding contribution to the development of many deep learning research fields. Recently, researchers in the acoustic signal processing field noticed its success and leveraged contrastive learning for better music representation. Typically, existing approaches maximize the similarity between two distorted audio segments sampled from the same music. In other words, they ensure a semantic agreement at the music level. However, those coarse-grained methods neglect some inessential or noisy elements at the frame level, which may be detrimental to the model to learn the effective representation of music. Towards this end, this paper proposes a novel Positive-nEgative frame mask for Music Representation based on the contrastive learning framework, abbreviated as PEMR. Concretely, PEMR incorporates a Positive-Negative Mask Generation module, which leverages transformer blocks to generate frame masks on the Log-Mel spectrogram. We can generate self-augmented negative and positive samples by masking important components or inessential components, respectively. We devise a novel contrastive learning objective to accommodate both self-augmented positives/negatives sampled from the same music. We conduct experiments on four public datasets. The experimental results of two music-related downstream tasks, music classification, and cover song identification, demonstrate the generalization ability and transferability of music representation learned by PEMR.

BoostMIS: Boosting Medical Image Semi-supervised Learning with Adaptive Pseudo Labeling and Informative Active Annotation

In this paper, we propose a novel semi-supervised learning (SSL) framework named BoostMIS that combines adaptive pseudo labeling and informative active annotation to unleash the potential of medical image SSL models: (1) BoostMIS can adaptively leverage the cluster assumption and consistency regularization of the unlabeled data according to the current learning status. This strategy can adaptively generate one-hot "hard" labels converted from task model predictions for better task model training. (2) For the unselected unlabeled images with low confidence, we introduce an Active learning (AL) algorithm to find the informative samples as the annotation candidates by exploiting virtual adversarial perturbation and model's density-aware entropy. These informative candidates are subsequently fed into the next training cycle for better SSL label propagation. Notably, the adaptive pseudo-labeling and informative active annotation form a learning closed-loop that are mutually collaborative to boost medical image SSL. To verify the effectiveness of the proposed method, we collected a metastatic epidural spinal cord compression (MESCC) dataset that aims to optimize MESCC diagnosis and classification for improved specialist referral and treatment. We conducted an extensive experimental study of BoostMIS on MESCC and another public dataset COVIDx. The experimental results verify our framework's effectiveness and generalisability for different medical image datasets with a significant improvement over various state-of-the-art methods.