Search

We propose AMP-Designer, an LLM-based foundation model approach for the rapid design of novel antimicrobial peptides (AMPs) with multiple desired properties. Within 11 days, AMP-Designer enables de novo design of 18 novel candidates with broad-spectrum potency against Gram-negative bacteria. Subsequent in vitro validation experiments demonstrate that almost all in silico recommended candidates exhibit notable antibacterial activity, yielding a 94.4% positive rate. Two of these candidates exhibit exceptional activity, minimal hemotoxicity, substantial stability in human plasma, and a low propensity of inducing antibiotic resistance as observed in murine lung infection experiments, showcasing their significant efficacy in reducing bacterial load by approximately one hundredfold. The entire process, from in silico design to in vitro and in vivo validation, is completed within a timeframe of 48 days. Moreover, AMP-Designer demonstrates its remarkable capability in designing specific AMPs to target strains with extremely limited labeled datasets. The most outstanding candidate against Propionibacterium acnes suggested by AMP-Designer exhibits an in vitro minimum inhibitory concentration value of 2.0 $\mu$g/ml. Through the integration of advanced machine learning methodologies such as contrastive prompt tuning, knowledge distillation, and reinforcement learning within the AMP-Designer framework, the process of designing AMPs demonstrates exceptional efficiency. This efficiency remains conspicuous even in the face of challenges posed by constraints arising from a scarcity of labeled data. These findings highlight the tremendous potential of AMP-Designer as a promising approach in combating the global health threat of antibiotic resistance., Comment: 43 pages, 6 figures, 5 tables. Due to the limitation "The abstract field cannot be longer than 1,920 characters", the abstract appearing here is slightly shorter than that in the PDF file

Recombinant adeno-associated virus (rAAV) vectors have revolutionized gene therapy, but their broad tropism and suboptimal transduction efficiency limit their clinical applications. To overcome these limitations, researchers have focused on designing and screening capsid libraries to identify improved vectors. However, the large sequence space and limited resources present challenges in identifying viable capsid variants. In this study, we propose an end-to-end diffusion model to generate capsid sequences with enhanced viability. Using publicly available AAV2 data, we generated 38,000 diverse AAV2 viral protein (VP) sequences, and evaluated 8,000 for viral selection. The results attested the superiority of our model compared to traditional methods. Additionally, in the absence of AAV9 capsid data, apart from one wild-type sequence, we used the same model to directly generate a number of viable sequences with up to 9 mutations. we transferred the remaining 30,000 samples to the AAV9 domain. Furthermore, we conducted mutagenesis on AAV9 VP hypervariable regions VI and V, contributing to the continuous improvement of the AAV9 VP sequence. This research represents a significant advancement in the design and functional validation of rAAV vectors, offering innovative solutions to enhance specificity and transduction efficiency in gene therapy applications.

Conformation Generation is a fundamental problem in drug discovery and cheminformatics. And organic molecule conformation generation, particularly in vacuum and protein pocket environments, is most relevant to drug design. Recently, with the development of geometric neural networks, the data-driven schemes have been successfully applied in this field, both for molecular conformation generation (in vacuum) and binding pose generation (in protein pocket). The former beats the traditional ETKDG method, while the latter achieves similar accuracy compared with the widely used molecular docking software. Although these methods have shown promising results, some researchers have recently questioned whether deep learning (DL) methods perform better in molecular conformation generation via a parameter-free method. To our surprise, what they have designed is some kind analogous to the famous infinite monkey theorem, the monkeys that are even equipped with physics education. To discuss the feasibility of their proving, we constructed a real infinite stochastic monkey for molecular conformation generation, showing that even with a more stochastic sampler for geometry generation, the coverage of the benchmark QM-computed conformations are higher than those of most DL-based methods. By extending their physical monkey algorithm for binding pose prediction, we also discover that the successful docking rate also achieves near-best performance among existing DL-based docking models. Thus, though their conclusions are right, their proof process needs more concern.

Masked image modeling (MIM) has shown great promise for self-supervised learning (SSL) yet been criticized for learning inefficiency. We believe the insufficient utilization of training signals should be responsible. To alleviate this issue, we introduce a conceptually simple yet learning-efficient MIM training scheme, termed Disjoint Masking with Joint Distillation (DMJD). For disjoint masking (DM), we sequentially sample multiple masked views per image in a mini-batch with the disjoint regulation to raise the usage of tokens for reconstruction in each image while keeping the masking rate of each view. For joint distillation (JD), we adopt a dual branch architecture to respectively predict invisible (masked) and visible (unmasked) tokens with superior learning targets. Rooting in orthogonal perspectives for training efficiency improvement, DM and JD cooperatively accelerate the training convergence yet not sacrificing the model generalization ability. Concretely, DM can train ViT with half of the effective training epochs (3.7 times less time-consuming) to report competitive performance. With JD, our DMJD clearly improves the linear probing classification accuracy over ConvMAE by 5.8%. On fine-grained downstream tasks like semantic segmentation, object detection, etc., our DMJD also presents superior generalization compared with state-of-the-art SSL methods. The code and model will be made public at https://github.com/mx-mark/DMJD.

Translation-based knowledge graph embedding has been one of the most important branches for knowledge representation learning since TransE came out. Although many translation-based approaches have achieved some progress in recent years, the performance was still unsatisfactory. This paper proposes a novel knowledge graph embedding method named TripleRE with two versions. The first version of TripleRE creatively divide the relationship vector into three parts. The second version takes advantage of the concept of residual and achieves better performance. In addition, attempts on using NodePiece to encode entities achieved promising results in reducing the parametric size, and solved the problems of scalability. Experiments show that our approach achieved state-of-the-art performance on the large-scale knowledge graph dataset, and competitive performance on other datasets.

Conventional representation learning algorithms for knowledge graphs (KG) map each entity to a unique embedding vector, ignoring the rich information contained in the neighborhood. We propose a method named StarGraph, which gives a novel way to utilize the neighborhood information for large-scale knowledge graphs to obtain entity representations. An incomplete two-hop neighborhood subgraph for each target node is at first generated, then processed by a modified self-attention network to obtain the entity representation, which is used to replace the entity embedding in conventional methods. We achieved SOTA performance on ogbl-wikikg2 and got competitive results on fb15k-237. The experimental results proves that StarGraph is efficient in parameters, and the improvement made on ogbl-wikikg2 demonstrates its great effectiveness of representation learning on large-scale knowledge graphs. The code is now available at \url{https://github.com/hzli-ucas/StarGraph}., Comment: Under review in ICLR 2023 (https://openreview.net/forum?id=mTOB_VK_BWk)

Vision-language pre-training (VLP) on large-scale datasets has shown premier performance on various downstream tasks. In contrast to plenty of available benchmarks with English corpus, large-scale pre-training datasets and downstream datasets with Chinese corpus remain largely unexplored. In this work, we build a large-scale high-quality Chinese Cross-Modal Benchmark named CCMB for the research community, which contains the currently largest public pre-training dataset Zero and five human-annotated fine-tuning datasets for downstream tasks. Zero contains 250 million images paired with 750 million text descriptions, plus two of the five fine-tuning datasets are also currently the largest ones for Chinese cross-modal downstream tasks. Along with the CCMB, we also develop a VLP framework named R2D2, applying a pre-Ranking + Ranking strategy to learn powerful vision-language representations and a two-way distillation method (i.e., target-guided Distillation and feature-guided Distillation) to further enhance the learning capability. With the Zero and the R2D2 VLP framework, we achieve state-of-the-art performance on twelve downstream datasets from five broad categories of tasks including image-text retrieval, image-text matching, image caption, text-to-image generation, and zero-shot image classification. The datasets, models, and codes are available at https://github.com/yuxie11/R2D2

Historically lower-level tasks such as automatic speech recognition (ASR) and speaker identification are the main focus in the speech field. Interest has been growing in higher-level spoken language understanding (SLU) tasks recently, like sentiment analysis (SA). However, improving performances on SLU tasks remains a big challenge. Basically, there are two main methods for SLU tasks: (1) Two-stage method, which uses a speech model to transfer speech to text, then uses a language model to get the results of downstream tasks; (2) One-stage method, which just fine-tunes a pre-trained speech model to fit in the downstream tasks. The first method loses emotional cues such as intonation, and causes recognition errors during ASR process, and the second one lacks necessary language knowledge. In this paper, we propose the Wave BERT (WaBERT), a novel end-to-end model combining the speech model and the language model for SLU tasks. WaBERT is based on the pre-trained speech and language model, hence training from scratch is not needed. We also set most parameters of WaBERT frozen during training. By introducing WaBERT, audio-specific information and language knowledge are integrated in the short-time and low-resource training process to improve results on the dev dataset of SLUE SA tasks by 1.15% of recall score and 0.82% of F1 score. Additionally, we modify the serial Continuous Integrate-and-Fire (CIF) mechanism to achieve the monotonic alignment between the speech and text modalities.

The 2nd Anti-UAV Workshop \& Challenge aims to encourage research in developing novel and accurate methods for multi-scale object tracking. The Anti-UAV dataset used for the Anti-UAV Challenge has been publicly released. There are two subsets in the dataset, $i.e.$, the test-dev subset and test-challenge subset. Both subsets consist of 140 thermal infrared video sequences, spanning multiple occurrences of multi-scale UAVs. Around 24 participating teams from the globe competed in the 2nd Anti-UAV Challenge. In this paper, we provide a brief summary of the 2nd Anti-UAV Workshop \& Challenge including brief introductions to the top three methods.The submission leaderboard will be reopened for researchers that are interested in the Anti-UAV challenge. The benchmark dataset and other information can be found at: https://anti-uav.github.io/.

How can a single fully convolutional neural network (FCN) perform on object detection? We introduce DenseBox, a unified end-to-end FCN framework that directly predicts bounding boxes and object class confidences through all locations and scales of an image. Our contribution is two-fold. First, we show that a single FCN, if designed and optimized carefully, can detect multiple different objects extremely accurately and efficiently. Second, we show that when incorporating with landmark localization during multi-task learning, DenseBox further improves object detection accuray. We present experimental results on public benchmark datasets including MALF face detection and KITTI car detection, that indicate our DenseBox is the state-of-the-art system for detecting challenging objects such as faces and cars.

Face Recognition has been studied for many decades. As opposed to traditional hand-crafted features such as LBP and HOG, much more sophisticated features can be learned automatically by deep learning methods in a data-driven way. In this paper, we propose a two-stage approach that combines a multi-patch deep CNN and deep metric learning, which extracts low dimensional but very discriminative features for face verification and recognition. Experiments show that this method outperforms other state-of-the-art methods on LFW dataset, achieving 99.77% pair-wise verification accuracy and significantly better accuracy under other two more practical protocols. This paper also discusses the importance of data size and the number of patches, showing a clear path to practical high-performance face recognition systems in real world.