Computer Science Program, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology, Center of Excellence for Smart Health, Center of Excellence on Generative AI, King Abdullah University of Science and Technology
Abstract:Existing PLMs generate protein sequences based on a single-condition constraint from a specific modality, struggling to simultaneously satisfy multiple constraints across different modalities. In this work, we introduce CFP-Gen, a novel diffusion language model for Combinatorial Functional Protein GENeration. CFP-Gen facilitates the de novo protein design by integrating multimodal conditions with functional, sequence, and structural constraints. Specifically, an Annotation-Guided Feature Modulation (AGFM) module is introduced to dynamically adjust the protein feature distribution based on composable functional annotations, e.g., GO terms, IPR domains and EC numbers. Meanwhile, the Residue-Controlled Functional Encoding (RCFE) module captures residue-wise interaction to ensure more precise control. Additionally, off-the-shelf 3D structure encoders can be seamlessly integrated to impose geometric constraints. We demonstrate that CFP-Gen enables high-throughput generation of novel proteins with functionality comparable to natural proteins, while achieving a high success rate in designing multifunctional proteins. Code and data available at https://github.com/yinjunbo/cfpgen.
Abstract:Chromosome analysis is vital for diagnosing genetic disorders and guiding cancer therapy decisions through the identification of somatic clonal aberrations. However, developing an AI model are hindered by the overwhelming complexity and diversity of chromosomal abnormalities, requiring extensive annotation efforts, while automated methods remain task-specific and lack generalizability due to the scarcity of comprehensive datasets spanning diverse resource conditions. Here, we introduce CHROMA, a foundation model for cytogenomics, designed to overcome these challenges by learning generalizable representations of chromosomal abnormalities. Pre-trained on over 84,000 specimens (~4 million chromosomal images) via self-supervised learning, CHROMA outperforms other methods across all types of abnormalities, even when trained on fewer labelled data and more imbalanced datasets. By facilitating comprehensive mapping of instability and clonal leisons across various aberration types, CHROMA offers a scalable and generalizable solution for reliable and automated clinical analysis, reducing the annotation workload for experts and advancing precision oncology through the early detection of rare genomic abnormalities, enabling broad clinical AI applications and making advanced genomic analysis more accessible.
Abstract:The advent of single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) offers an innovative perspective for deciphering regulatory mechanisms by assembling a vast repository of single-cell chromatin accessibility data. While foundation models have achieved significant success in single-cell transcriptomics, there is currently no foundation model for scATAC-seq that supports zero-shot high-quality cell identification and comprehensive multi-omics analysis simultaneously. Key challenges lie in the high dimensionality and sparsity of scATAC-seq data, as well as the lack of a standardized schema for representing open chromatin regions (OCRs). Here, we present \textbf{ChromFound}, a foundation model tailored for scATAC-seq. ChromFound utilizes a hybrid architecture and genome-aware tokenization to effectively capture genome-wide long contexts and regulatory signals from dynamic chromatin landscapes. Pretrained on 1.97 million cells from 30 tissues and 6 disease conditions, ChromFound demonstrates broad applicability across 6 diverse tasks. Notably, it achieves robust zero-shot performance in generating universal cell representations and exhibits excellent transferability in cell type annotation and cross-omics prediction. By uncovering enhancer-gene links undetected by existing computational methods, ChromFound offers a promising framework for understanding disease risk variants in the noncoding genome.
Abstract:Accurate lymph node metastasis (LNM) assessment in rectal cancer is essential for treatment planning, yet current MRI-based evaluation shows unsatisfactory accuracy, leading to suboptimal clinical decisions. Developing automated systems also faces significant obstacles, primarily the lack of node-level annotations. Previous methods treat lymph nodes as isolated entities rather than as an interconnected system, overlooking valuable spatial and contextual information. To solve this problem, we present WeGA, a novel weakly-supervised global-local affinity learning framework that addresses these challenges through three key innovations: 1) a dual-branch architecture with DINOv2 backbone for global context and residual encoder for local node details; 2) a global-local affinity extractor that aligns features across scales through cross-attention fusion; and 3) a regional affinity loss that enforces structural coherence between classification maps and anatomical regions. Experiments across one internal and two external test centers demonstrate that WeGA outperforms existing methods, achieving AUCs of 0.750, 0.822, and 0.802 respectively. By effectively modeling the relationships between individual lymph nodes and their collective context, WeGA provides a more accurate and generalizable approach for lymph node metastasis prediction, potentially enhancing diagnostic precision and treatment selection for rectal cancer patients.
Abstract:Accurate multi-modal medical image translation requires ha-rmonizing global anatomical semantics and local structural fidelity, a challenge complicated by intermodality information loss and structural distortion. We propose ABS-Mamba, a novel architecture integrating the Segment Anything Model 2 (SAM2) for organ-aware semantic representation, specialized convolutional neural networks (CNNs) for preserving modality-specific edge and texture details, and Mamba's selective state-space modeling for efficient long- and short-range feature dependencies. Structurally, our dual-resolution framework leverages SAM2's image encoder to capture organ-scale semantics from high-resolution inputs, while a parallel CNNs branch extracts fine-grained local features. The Robust Feature Fusion Network (RFFN) integrates these epresentations, and the Bidirectional Mamba Residual Network (BMRN) models spatial dependencies using spiral scanning and bidirectional state-space dynamics. A three-stage skip fusion decoder enhances edge and texture fidelity. We employ Efficient Low-Rank Adaptation (LoRA+) fine-tuning to enable precise domain specialization while maintaining the foundational capabilities of the pre-trained components. Extensive experimental validation on the SynthRAD2023 and BraTS2019 datasets demonstrates that ABS-Mamba outperforms state-of-the-art methods, delivering high-fidelity cross-modal synthesis that preserves anatomical semantics and structural details to enhance diagnostic accuracy in clinical applications. The code is available at https://github.com/gatina-yone/ABS-Mamba
Abstract:The development of model ensemble attacks has significantly improved the transferability of adversarial examples, but this progress also poses severe threats to the security of deep neural networks. Existing methods, however, face two critical challenges: insufficient capture of shared gradient directions across models and a lack of adaptive weight allocation mechanisms. To address these issues, we propose a novel method Harmonized Ensemble for Adversarial Transferability (HEAT), which introduces domain generalization into adversarial example generation for the first time. HEAT consists of two key modules: Consensus Gradient Direction Synthesizer, which uses Singular Value Decomposition to synthesize shared gradient directions; and Dual-Harmony Weight Orchestrator which dynamically balances intra-domain coherence, stabilizing gradients within individual models, and inter-domain diversity, enhancing transferability across models. Experimental results demonstrate that HEAT significantly outperforms existing methods across various datasets and settings, offering a new perspective and direction for adversarial attack research.
Abstract:Large language models (LLMs) have demonstrated remarkable capabilities, especially the recent advancements in reasoning, such as o1 and o3, pushing the boundaries of AI. Despite these impressive achievements in mathematics and coding, the reasoning abilities of LLMs in domains requiring cryptographic expertise remain underexplored. In this paper, we introduce CipherBank, a comprehensive benchmark designed to evaluate the reasoning capabilities of LLMs in cryptographic decryption tasks. CipherBank comprises 2,358 meticulously crafted problems, covering 262 unique plaintexts across 5 domains and 14 subdomains, with a focus on privacy-sensitive and real-world scenarios that necessitate encryption. From a cryptographic perspective, CipherBank incorporates 3 major categories of encryption methods, spanning 9 distinct algorithms, ranging from classical ciphers to custom cryptographic techniques. We evaluate state-of-the-art LLMs on CipherBank, e.g., GPT-4o, DeepSeek-V3, and cutting-edge reasoning-focused models such as o1 and DeepSeek-R1. Our results reveal significant gaps in reasoning abilities not only between general-purpose chat LLMs and reasoning-focused LLMs but also in the performance of current reasoning-focused models when applied to classical cryptographic decryption tasks, highlighting the challenges these models face in understanding and manipulating encrypted data. Through detailed analysis and error investigations, we provide several key observations that shed light on the limitations and potential improvement areas for LLMs in cryptographic reasoning. These findings underscore the need for continuous advancements in LLM reasoning capabilities.
Abstract:Artificial intelligence (AI) systems, particularly those based on deep learning models, have increasingly achieved expert-level performance in medical applications. However, there is growing concern that such AI systems may reflect and amplify human bias, and reduce the quality of their performance in historically under-served populations. The fairness issue has attracted considerable research interest in the medical imaging classification field, yet it remains understudied in the text generation domain. In this study, we investigate the fairness problem in text generation within the medical field and observe significant performance discrepancies across different races, sexes, and age groups, including intersectional groups, various model scales, and different evaluation metrics. To mitigate this fairness issue, we propose an algorithm that selectively optimizes those underperformed groups to reduce bias. The selection rules take into account not only word-level accuracy but also the pathology accuracy to the target reference, while ensuring that the entire process remains fully differentiable for effective model training. Our evaluations across multiple backbones, datasets, and modalities demonstrate that our proposed algorithm enhances fairness in text generation without compromising overall performance. Specifically, the disparities among various groups across different metrics were diminished by more than 30% with our algorithm, while the relative change in text generation accuracy was typically within 2%. By reducing the bias generated by deep learning models, our proposed approach can potentially alleviate concerns about the fairness and reliability of text generation diagnosis in medical domain. Our code is publicly available to facilitate further research at https://github.com/iriscxy/GenFair.
Abstract:While the diffusion transformer (DiT) has become a focal point of interest in recent years, its application in low-light image enhancement remains a blank area for exploration. Current methods recover the details from low-light images while inevitably amplifying the noise in images, resulting in poor visual quality. In this paper, we firstly introduce DiT into the low-light enhancement task and design a novel Structure-guided Diffusion Transformer based Low-light image enhancement (SDTL) framework. We compress the feature through wavelet transform to improve the inference efficiency of the model and capture the multi-directional frequency band. Then we propose a Structure Enhancement Module (SEM) that uses structural prior to enhance the texture and leverages an adaptive fusion strategy to achieve more accurate enhancement effect. In Addition, we propose a Structure-guided Attention Block (SAB) to pay more attention to texture-riched tokens and avoid interference from noisy areas in noise prediction. Extensive qualitative and quantitative experiments demonstrate that our method achieves SOTA performance on several popular datasets, validating the effectiveness of SDTL in improving image quality and the potential of DiT in low-light enhancement tasks.
Abstract:In multi-agent safety-critical scenarios, traditional autonomous driving frameworks face significant challenges in balancing safety constraints and task performance. These frameworks struggle to quantify dynamic interaction risks in real-time and depend heavily on manual rules, resulting in low computational efficiency and conservative strategies. To address these limitations, we propose a Dynamic Residual Safe Reinforcement Learning (DRS-RL) framework grounded in a safety-enhanced networked Markov decision process. It's the first time that the weak-to-strong theory is introduced into multi-agent decision-making, enabling lightweight dynamic calibration of safety boundaries via a weak-to-strong safety correction paradigm. Based on the multi-agent dynamic conflict zone model, our framework accurately captures spatiotemporal coupling risks among heterogeneous traffic participants and surpasses the static constraints of conventional geometric rules. Moreover, a risk-aware prioritized experience replay mechanism mitigates data distribution bias by mapping risk to sampling probability. Experimental results reveal that the proposed method significantly outperforms traditional RL algorithms in safety, efficiency, and comfort. Specifically, it reduces the collision rate by up to 92.17%, while the safety model accounts for merely 27% of the main model's parameters.