A Generalist Cross-Domain Molecular Learning Framework for Structure-Based Drug Discovery

Structure-based drug discovery (SBDD) is a systematic scientific process that develops new drugs by leveraging the detailed physical structure of the target protein. Recent advancements in pre-trained models for biomolecules have demonstrated remarkable success across various biochemical applications, including drug discovery and protein engineering. However, in most approaches, the pre-trained models primarily focus on the characteristics of either small molecules or proteins, without delving into their binding interactions which are essential cross-domain relationships pivotal to SBDD. To fill this gap, we propose a general-purpose foundation model named BIT (an abbreviation for Biomolecular Interaction Transformer), which is capable of encoding a range of biochemical entities, including small molecules, proteins, and protein-ligand complexes, as well as various data formats, encompassing both 2D and 3D structures. Specifically, we introduce Mixture-of-Domain-Experts (MoDE) to handle the biomolecules from diverse biochemical domains and Mixture-of-Structure-Experts (MoSE) to capture positional dependencies in the molecular structures. The proposed mixture-of-experts approach enables BIT to achieve both deep fusion and domain-specific encoding, effectively capturing fine-grained molecular interactions within protein-ligand complexes. Then, we perform cross-domain pre-training on the shared Transformer backbone via several unified self-supervised denoising tasks. Experimental results on various benchmarks demonstrate that BIT achieves exceptional performance in downstream tasks, including binding affinity prediction, structure-based virtual screening, and molecular property prediction.

GENERator: A Long-Context Generative Genomic Foundation Model

Advancements in DNA sequencing technologies have significantly improved our ability to decode genomic sequences. However, the prediction and interpretation of these sequences remain challenging due to the intricate nature of genetic material. Large language models (LLMs) have introduced new opportunities for biological sequence analysis. Recent developments in genomic language models have underscored the potential of LLMs in deciphering DNA sequences. Nonetheless, existing models often face limitations in robustness and application scope, primarily due to constraints in model structure and training data scale. To address these limitations, we present GENERator, a generative genomic foundation model featuring a context length of 98k base pairs (bp) and 1.2B parameters. Trained on an expansive dataset comprising 386B bp of eukaryotic DNA, the GENERator demonstrates state-of-the-art performance across both established and newly proposed benchmarks. The model adheres to the central dogma of molecular biology, accurately generating protein-coding sequences that translate into proteins structurally analogous to known families. It also shows significant promise in sequence optimization, particularly through the prompt-responsive generation of promoter sequences with specific activity profiles. These capabilities position the GENERator as a pivotal tool for genomic research and biotechnological advancement, enhancing our ability to interpret and predict complex biological systems and enabling precise genomic interventions.

ProtCLIP: Function-Informed Protein Multi-Modal Learning

Multi-modality pre-training paradigm that aligns protein sequences and biological descriptions has learned general protein representations and achieved promising performance in various downstream applications. However, these works were still unable to replicate the extraordinary success of language-supervised visual foundation models due to the ineffective usage of aligned protein-text paired data and the lack of an effective function-informed pre-training paradigm. To address these issues, this paper curates a large-scale protein-text paired dataset called ProtAnno with a property-driven sampling strategy, and introduces a novel function-informed protein pre-training paradigm. Specifically, the sampling strategy determines selecting probability based on the sample confidence and property coverage, balancing the data quality and data quantity in face of large-scale noisy data. Furthermore, motivated by significance of the protein specific functional mechanism, the proposed paradigm explicitly model protein static and dynamic functional segments by two segment-wise pre-training objectives, injecting fine-grained information in a function-informed manner. Leveraging all these innovations, we develop ProtCLIP, a multi-modality foundation model that comprehensively represents function-aware protein embeddings. On 22 different protein benchmarks within 5 types, including protein functionality classification, mutation effect prediction, cross-modal transformation, semantic similarity inference and protein-protein interaction prediction, our ProtCLIP consistently achieves SOTA performance, with remarkable improvements of 75% on average in five cross-modal transformation benchmarks, 59.9% in GO-CC and 39.7% in GO-BP protein function prediction. The experimental results verify the extraordinary potential of ProtCLIP serving as the protein multi-modality foundation model.

RS-vHeat: Heat Conduction Guided Efficient Remote Sensing Foundation Model

Remote sensing foundation models largely break away from the traditional paradigm of designing task-specific models, offering greater scalability across multiple tasks. However, they face challenges such as low computational efficiency and limited interpretability, especially when dealing with high-resolution remote sensing images. To overcome these, we draw inspiration from heat conduction, a physical process modeling local heat diffusion. Building on this idea, we are the first to explore the potential of using the parallel computing model of heat conduction to simulate the local region correlations in high-resolution remote sensing images, and introduce RS-vHeat, an efficient multi-modal remote sensing foundation model. Specifically, RS-vHeat 1) applies the Heat Conduction Operator (HCO) with a complexity of $O(N^{1.5})$ and a global receptive field, reducing computational overhead while capturing remote sensing object structure information to guide heat diffusion; 2) learns the frequency distribution representations of various scenes through a self-supervised strategy based on frequency domain hierarchical masking and multi-domain reconstruction; 3) significantly improves efficiency and performance over state-of-the-art techniques across 4 tasks and 10 datasets. Compared to attention-based remote sensing foundation models, we reduces memory consumption by 84%, decreases FLOPs by 24% and improves throughput by 2.7 times.

NavAgent: Multi-scale Urban Street View Fusion For UAV Embodied Vision-and-Language Navigation

Vision-and-Language Navigation (VLN), as a widely discussed research direction in embodied intelligence, aims to enable embodied agents to navigate in complicated visual environments through natural language commands. Most existing VLN methods focus on indoor ground robot scenarios. However, when applied to UAV VLN in outdoor urban scenes, it faces two significant challenges. First, urban scenes contain numerous objects, which makes it challenging to match fine-grained landmarks in images with complex textual descriptions of these landmarks. Second, overall environmental information encompasses multiple modal dimensions, and the diversity of representations significantly increases the complexity of the encoding process. To address these challenges, we propose NavAgent, the first urban UAV embodied navigation model driven by a large Vision-Language Model. NavAgent undertakes navigation tasks by synthesizing multi-scale environmental information, including topological maps (global), panoramas (medium), and fine-grained landmarks (local). Specifically, we utilize GLIP to build a visual recognizer for landmark capable of identifying and linguisticizing fine-grained landmarks. Subsequently, we develop dynamically growing scene topology map that integrate environmental information and employ Graph Convolutional Networks to encode global environmental data. In addition, to train the visual recognizer for landmark, we develop NavAgent-Landmark2K, the first fine-grained landmark dataset for real urban street scenes. In experiments conducted on the Touchdown and Map2seq datasets, NavAgent outperforms strong baseline models. The code and dataset will be released to the community to facilitate the exploration and development of outdoor VLN.

TokenSelect: Efficient Long-Context Inference and Length Extrapolation for LLMs via Dynamic Token-Level KV Cache Selection

With the development of large language models (LLMs), the ability to handle longer contexts has become a key capability for Web applications such as cross-document understanding and LLM-powered search systems. However, this progress faces two major challenges: performance degradation due to sequence lengths out-of-distribution, and excessively long inference times caused by the quadratic computational complexity of attention. These issues hinder the application of LLMs in long-context scenarios. In this paper, we propose Dynamic Token-Level KV Cache Selection (TokenSelect), a model-agnostic, training-free method for efficient and accurate long-context inference. TokenSelect builds upon the observation of non-contiguous attention sparsity, using Query-Key dot products to measure per-head KV Cache criticality at token-level. By per-head soft voting mechanism, TokenSelect selectively involves a small number of critical KV cache tokens in the attention calculation without sacrificing accuracy. To further accelerate TokenSelect, we designed the Selection Cache based on observations of consecutive Query similarity and implemented efficient dot product kernel, significantly reducing the overhead of token selection. A comprehensive evaluation of TokenSelect demonstrates up to 23.84x speedup in attention computation and up to 2.28x acceleration in end-to-end latency, while providing superior performance compared to state-of-the-art long-context inference methods.

Structure-Enhanced Protein Instruction Tuning: Towards General-Purpose Protein Understanding

Proteins, as essential biomolecules, play a central role in biological processes, including metabolic reactions and DNA replication. Accurate prediction of their properties and functions is crucial in biological applications. Recent development of protein language models (pLMs) with supervised fine tuning provides a promising solution to this problem. However, the fine-tuned model is tailored for particular downstream prediction task, and achieving general-purpose protein understanding remains a challenge. In this paper, we introduce Structure-Enhanced Protein Instruction Tuning (SEPIT) framework to bridge this gap. Our approach integrates a noval structure-aware module into pLMs to inform them with structural knowledge, and then connects these enhanced pLMs to large language models (LLMs) to generate understanding of proteins. In this framework, we propose a novel two-stage instruction tuning pipeline that first establishes a basic understanding of proteins through caption-based instructions and then refines this understanding using a mixture of experts (MoEs) to learn more complex properties and functional information with the same amount of activated parameters. Moreover, we construct the largest and most comprehensive protein instruction dataset to date, which allows us to train and evaluate the general-purpose protein understanding model. Extensive experimental results on open-ended generation and closed-set answer tasks demonstrate the superior performance of SEPIT over both closed-source general LLMs and open-source LLMs trained with protein knowledge.

Prompt-and-Transfer: Dynamic Class-aware Enhancement for Few-shot Segmentation

For more efficient generalization to unseen domains (classes), most Few-shot Segmentation (FSS) would directly exploit pre-trained encoders and only fine-tune the decoder, especially in the current era of large models. However, such fixed feature encoders tend to be class-agnostic, inevitably activating objects that are irrelevant to the target class. In contrast, humans can effortlessly focus on specific objects in the line of sight. This paper mimics the visual perception pattern of human beings and proposes a novel and powerful prompt-driven scheme, called ``Prompt and Transfer" (PAT), which constructs a dynamic class-aware prompting paradigm to tune the encoder for focusing on the interested object (target class) in the current task. Three key points are elaborated to enhance the prompting: 1) Cross-modal linguistic information is introduced to initialize prompts for each task. 2) Semantic Prompt Transfer (SPT) that precisely transfers the class-specific semantics within the images to prompts. 3) Part Mask Generator (PMG) that works in conjunction with SPT to adaptively generate different but complementary part prompts for different individuals. Surprisingly, PAT achieves competitive performance on 4 different tasks including standard FSS, Cross-domain FSS (e.g., CV, medical, and remote sensing domains), Weak-label FSS, and Zero-shot Segmentation, setting new state-of-the-arts on 11 benchmarks.

AeroVerse: UAV-Agent Benchmark Suite for Simulating, Pre-training, Finetuning, and Evaluating Aerospace Embodied World Models

Aerospace embodied intelligence aims to empower unmanned aerial vehicles (UAVs) and other aerospace platforms to achieve autonomous perception, cognition, and action, as well as egocentric active interaction with humans and the environment. The aerospace embodied world model serves as an effective means to realize the autonomous intelligence of UAVs and represents a necessary pathway toward aerospace embodied intelligence. However, existing embodied world models primarily focus on ground-level intelligent agents in indoor scenarios, while research on UAV intelligent agents remains unexplored. To address this gap, we construct the first large-scale real-world image-text pre-training dataset, AerialAgent-Ego10k, featuring urban drones from a first-person perspective. We also create a virtual image-text-pose alignment dataset, CyberAgent Ego500k, to facilitate the pre-training of the aerospace embodied world model. For the first time, we clearly define 5 downstream tasks, i.e., aerospace embodied scene awareness, spatial reasoning, navigational exploration, task planning, and motion decision, and construct corresponding instruction datasets, i.e., SkyAgent-Scene3k, SkyAgent-Reason3k, SkyAgent-Nav3k and SkyAgent-Plan3k, and SkyAgent-Act3k, for fine-tuning the aerospace embodiment world model. Simultaneously, we develop SkyAgentEval, the downstream task evaluation metrics based on GPT-4, to comprehensively, flexibly, and objectively assess the results, revealing the potential and limitations of 2D/3D visual language models in UAV-agent tasks. Furthermore, we integrate over 10 2D/3D visual-language models, 2 pre-training datasets, 5 finetuning datasets, more than 10 evaluation metrics, and a simulator into the benchmark suite, i.e., AeroVerse, which will be released to the community to promote exploration and development of aerospace embodied intelligence.

Twin Deformable Point Convolutions for Point Cloud Semantic Segmentation in Remote Sensing Scenes

Thanks to the application of deep learning technology in point cloud processing of the remote sensing field, point cloud segmentation has become a research hotspot in recent years, which can be applied to real-world 3D, smart cities, and other fields. Although existing solutions have made unprecedented progress, they ignore the inherent characteristics of point clouds in remote sensing fields that are strictly arranged according to latitude, longitude, and altitude, which brings great convenience to the segmentation of point clouds in remote sensing fields. To consider this property cleverly, we propose novel convolution operators, termed Twin Deformable point Convolutions (TDConvs), which aim to achieve adaptive feature learning by learning deformable sampling points in the latitude-longitude plane and altitude direction, respectively. First, to model the characteristics of the latitude-longitude plane, we propose a Cylinder-wise Deformable point Convolution (CyDConv) operator, which generates a two-dimensional cylinder map by constructing a cylinder-like grid in the latitude-longitude direction. Furthermore, to better integrate the features of the latitude-longitude plane and the spatial geometric features, we perform a multi-scale fusion of the extracted latitude-longitude features and spatial geometric features, and realize it through the aggregation of adjacent point features of different scales. In addition, a Sphere-wise Deformable point Convolution (SpDConv) operator is introduced to adaptively offset the sampling points in three-dimensional space by constructing a sphere grid structure, aiming at modeling the characteristics in the altitude direction. Experiments on existing popular benchmarks conclude that our TDConvs achieve the best segmentation performance, surpassing the existing state-of-the-art methods.