Large-scale tuberculosis (TB) screening is limited by the high cost and operational complexity of traditional diagnostics, creating a need for artificial-intelligence solutions. We propose DeepGB-TB, a non-invasive system that instantly assigns TB risk scores using only cough audio and basic demographic data. The model couples a lightweight one-dimensional convolutional neural network for audio processing with a gradient-boosted decision tree for tabular features. Its principal innovation is a Cross-Modal Bidirectional Cross-Attention module (CM-BCA) that iteratively exchanges salient cues between modalities, emulating the way clinicians integrate symptoms and risk factors. To meet the clinical priority of minimizing missed cases, we design a Tuberculosis Risk-Balanced Loss (TRBL) that places stronger penalties on false-negative predictions, thereby reducing high-risk misclassifications. DeepGB-TB is evaluated on a diverse dataset of 1,105 patients collected across seven countries, achieving an AUROC of 0.903 and an F1-score of 0.851, representing a new state of the art. Its computational efficiency enables real-time, offline inference directly on common mobile devices, making it ideal for low-resource settings. Importantly, the system produces clinically validated explanations that promote trust and adoption by frontline health workers. By coupling AI innovation with public-health requirements for speed, affordability, and reliability, DeepGB-TB offers a tool for advancing global TB control.

Sign language is the primary communication mode for 72 million hearing-impaired individuals worldwide, necessitating effective bidirectional Sign Language Production and Sign Language Translation systems. However, functional bidirectional systems require a unified linguistic environment, hindered by the lack of suitable unified datasets, particularly those providing the necessary pose information for accurate Sign Language Production (SLP) evaluation. Concurrently, current SLP evaluation methods like back-translation ignore pose accuracy, and high-quality coordinated generation remains challenging. To create this crucial environment and overcome these challenges, we introduce CNText2Sign and CNSign, which together constitute the first unified dataset aimed at supporting bidirectional accessibility systems for Chinese sign language; CNText2Sign provides 15,000 natural language-to-sign mappings and standardized skeletal keypoints for 8,643 vocabulary items supporting pose assessment. Building upon this foundation, we propose the AuraLLM model, which leverages a decoupled architecture with CNText2Sign's pose data for novel direct gesture accuracy assessment. The model employs retrieval augmentation and Cascading Vocabulary Resolution to handle semantic mapping and out-of-vocabulary words, and achieves all-scenario production with controllable coordination of gestures and facial expressions via pose-conditioned video synthesis. Concurrently, our Sign Language Translation model SignMST-C employs targeted self-supervised pretraining for dynamic feature capture, achieving new SOTA results on PHOENIX2014-T with BLEU-4 scores up to 32.08. AuraLLM establishes a strong performance baseline on CNText2Sign with a BLEU-4 score of 50.41 under direct evaluation.

Early detection of retinal lesions is critical for preventing vision loss. While supervised learning has shown promise, existing methods often rely on extensive labeled data, which is costly and difficult to obtain in medical applications. Unsupervised anomaly detection provides an attractive alternative by requiring only healthy retinal images and no abnormal annotations. However, current methods face significant challenges in modeling the complex structures of normal retinal anatomy, learning discriminative features for detecting subtle lesions, and capturing multi-scale features to handle anomalies of varying sizes – highlighting the need for holistic feature modeling that comprehensively represents both retinal anatomy and pathology. To address these challenges, we propose HolistAno, a novel unsupervised anomaly detection framework with holistic retinal modeling. HolistAno adopts a two-stage network architecture, incorporating a novel anomaly generator and a Balanced Mamba Scale Fusion (BMSF) module to effectively learn comprehensive retinal feature representations. This enables accurate detection of subtle lesions, diverse lesion types, and anomalies across multiple scales. Extensive experiments on five benchmark datasets demonstrate that HolistAno achieves state-of-the-art performance in both anomaly classification and localization tasks, with superior generalization and robustness across multiple datasets and cross-dataset scenarios compared to existing methods.

Artificial intelligence has achieved notable results in sign language recognition and translation. However, relatively few efforts have been made to significantly improve the quality of life for the 72 million hearing-impaired people worldwide. Sign language translation models, relying on video inputs, involves with large parameter sizes, making it time-consuming and computationally intensive to be deployed. This directly contributes to the scarcity of human-centered technology in this field. Additionally, the lack of datasets in sign language translation hampers research progress in this area. To address these, we first propose a cross-modal multi-knowledge distillation technique from 3D to 1D and a novel end-to-end pre-training text correction framework. Compared to other pre-trained models, our framework achieves significant advancements in correcting text output errors. Our model achieves a decrease in Word Error Rate (WER) of at least 1.4% on PHOENIX14 and PHOENIX14T datasets compared to the state-of-the-art CorrNet. Additionally, the TensorFlow Lite (TFLite) quantized model size is reduced to 12.93 MB, making it the smallest, fastest, and most accurate model to date. We have also collected and released extensive Chinese sign language datasets, and developed a specialized training vocabulary. To address the lack of research on data augmentation for landmark data, we have designed comparative experiments on various augmentation methods. Moreover, we performed a simulated deployment and prediction of our model on Intel platform CPUs and assessed the feasibility of deploying the model on other platforms.

In medical image analysis, multi-organ semi-supervised segmentation faces challenges such as insufficient labels and low contrast in soft tissues. To address these issues, existing studies typically employ semi-supervised segmentation techniques using pseudo-labeling and consistency regularization. However, these methods mainly rely on individual data samples for training, ignoring the rich neighborhood information present in the feature space. In this work, we argue that supervisory information can be directly extracted from the geometry of the feature space. Inspired by the density-based clustering hypothesis, we propose using feature density to locate sparse regions within feature clusters. Our goal is to increase intra-class compactness by addressing sparsity issues. To achieve this, we propose a Density-Aware Contrastive Learning (DACL) strategy, pushing anchored features in sparse regions towards cluster centers approximated by high-density positive samples, resulting in more compact clusters. Specifically, our method constructs density-aware neighbor graphs using labeled and unlabeled data samples to estimate feature density and locate sparse regions. We also combine label-guided co-training with density-guided geometric regularization to form complementary supervision for unlabeled data. Experiments on the Multi-Organ Segmentation Challenge dataset demonstrate that our proposed method outperforms state-of-the-art methods, highlighting its efficacy in medical image segmentation tasks.

The application of Contrastive Language-Image Pre-training (CLIP) in Weakly Supervised Semantic Segmentation (WSSS) research demonstrates powerful cross-modal semantic understanding capabilities. Existing methods attempt to optimize input text prompts for improved alignment of images and text, specifically by finely adjusting text prototypes to facilitate semantic matching. Nevertheless, given the modality gap between text and vision spaces, the text prototypes employed by these methods have not effectively established a close correspondence with pixel-level vision features. In this work, our theoretical analysis indicates that the inherent modality gap results in misalignment of text and region features, and that this gap cannot be sufficiently reduced by minimizing contrast loss in CLIP. To mitigate the impact of the modality gap, we propose a Vision Prototype Learning (VPL) framework, by introducing more representative vision prototypes. The core of this framework is to learn class-specific vision prototypes in vision space with the help of text prototypes, to capture high-quality localization maps. Moreover, we propose a regional semantic contrast module that contrasts regions embedding with corresponding prototypes, leading to more comprehensive and robust feature learning. Experimental results show that our proposed framework achieves state-of-the-art performance on two benchmark datasets.

Recent multimodal large language models (MLLMs) have demonstrated significant potential in open-ended conversation, generating more accurate and personalized responses. However, their abilities to memorize, recall, and reason in sustained interactions within real-world scenarios remain underexplored. This paper introduces MMRC, a Multi-Modal Real-world Conversation benchmark for evaluating six core open-ended abilities of MLLMs: information extraction, multi-turn reasoning, information update, image management, memory recall, and answer refusal. With data collected from real-world scenarios, MMRC comprises 5,120 conversations and 28,720 corresponding manually labeled questions, posing a significant challenge to existing MLLMs. Evaluations on 20 MLLMs in MMRC indicate an accuracy drop during open-ended interactions. We identify four common failure patterns: long-term memory degradation, inadequacies in updating factual knowledge, accumulated assumption of error propagation, and reluctance to “say no.” To mitigate these issues, we propose a simple yet effective NOTE-TAKING strategy, which can record key information from the conversation and remind the model during its responses, enhancing conversational capabilities. Experiments across six MLLMs demonstrate significant performance improvements.

Long-sequence causal reasoning seeks to uncover causal relationships within extended time series data but is hindered by complex dependencies and the challenges of validating causal links. To address the limitations of large-scale language models (e.g., GPT-4) in capturing intricate emotional causality within extended dialogues, we propose CauseMotion, an innovative framework combining emotional causal dynamic mapping with multimodal feature fusion. CauseMotion implements dynamic mapping through a sliding window mechanism and fusion strategies, while integrating audio features—vocal emotion, intensity, and speech rate—to enrich semantic representations. This design enables efficient retrieval of contextually relevant information and precise inference of emotional causal chains spanning multiple conversational turns. We constructed the first benchmark dataset for long-sequence emotional causal reasoning, featuring dialogues with over 70 turns. Experimental results show that CauseMotion significantly enhances emotional understanding and causal inference capabilities in large language models. A GLM-4 integrated with CauseMotion achieves an 8.7% improvement in causal accuracy over the original model and surpasses GPT-4o by 1.2%. On the DiaASQ dataset, CauseMotion-GLM-4 achieves state-of-the-art results in accuracy, F1 score, and causal reasoning accuracy.

Digital orthodontics increasingly depends on accurate 3D dental models, yet conventional intraoral scanning remains inaccessible in remote tele-orthodontics, which typically relies on sparse smartphone imagery. While 3D Gaussian Splatting (3DGS) shows promise for novel view synthesis, its application to the standard clinical triad of unposed anterior and bilateral buccal photographs is challenging. The limitations of sparse-view photometric supervision, combined with large baselines, inconsistent illumination, and specular surfaces, can destabilize simultaneous pose and geometry estimation, often inducing frequency bias and over-smoothed reconstructions that lose critical diagnostic details. To address these issues, we propose Dental3R, a pose-free, graph-guided pipeline for robust, highfidelity reconstruction from sparse intraoral photographs. Our method first constructs a Geometry-Aware Pairing Strategy (GAPS) to select a compact subgraph of high-value image pairs, improving correspondence matching, stabilizing geometry initialization, and reducing memory usage. Leveraging on the recovered poses and point cloud, we train the 3DGS model with a wavelet-regularized objective. By enforcing band-limited fidelity via a discrete wavelet transform, our approach preserves fine enamel boundaries and interproximal edges while suppressing high-frequency artifacts. We validate our approach on a largescale dataset of 950 clinical cases and an additional video-based test set of 195 cases, demonstrating that Dental3R effectively handles sparse, unposed inputs and achieves superior novel-view synthesis quality over state-of-the-art methods.

Reliable 3D-2D alignment between intraoral scan (IOS) models and lateral cephalometric radiographs is critical for orthodontic diagnosis, yet conventional intensity-driven registration methods struggle under real clinical conditions, where cephalograms exhibit magnification, distortion, low-contrast dental crowns, and acquisition-dependent variation. These factors hinder the stability of appearance-based metrics and often lead to convergence failures or anatomically implausible alignments. To address these limitations, we propose DentalSCR, named for its silhouette-to-contour registration scheme, a pose-stable and contour-guided framework for accurate and interpretable alignment that achieves state-of-the-art performance. Our method constructs a U-Midline Dental Axis (UMDA) to establish a unified cross-arch anatomical coordinate system, stabilizing initialization and standardizing projection geometry across cases. Using this reference frame, we generate radiograph-like projections via a surface-based DRR (Digitally Reconstructed Radiograph) formulation with coronal-axis perspective and Gaussian splatting, which preserves clinically accurate magnification and emphasizes external silhouettes. Registration is formulated as a 2D similarity transform optimized with a symmetric bidirectional Chamfer distance under a hierarchical coarse-to-fine schedule, enabling both large capture range and subpixel-level contour agreement. We evaluate DentalSCR on 34 expert-annotated cases. Results demonstrate substantial reductions in landmark error, particularly at posterior teeth, tighter lower-jaw dispersion, and low Chamfer and controlled Hausdorff distances. These findings indicate that DentalSCR robustly handles real-world cephalograms and delivers high-fidelity, clinically inspectable 3D-2D alignment, consistently outperforming baselines and establishing a new state-of-the-art.

Segment Anything Model (SAM) demonstrates powerful zero-shot capabilities; however, its accuracy and robustness significantly decrease when applied to medical image segmentation. Existing methods address this issue through modality fusion, integrating textual and image information to provide more detailed priors. In this study, we argue that the granularity of text and the domain gap affect the accuracy of the priors. Furthermore, the discrepancy between high-level abstract semantics and pixel-level boundary details in images can introduce noise into the fusion process. To address this, we propose Prior-Guided SAM (PG-SAM), which employs a fine-grained modality prior aligner to leverage specialized medical knowledge for better modality alignment. The core of our method lies in efficiently addressing the domain gap with fine-grained text from a medical large language model (LLM). Meanwhile, it also enhances the priors' quality after modality alignment, ensuring more accurate segmentation. In addition, our decoder enhances the model's expressive capabilities through multi-level feature fusion and iterative mask optimizer operations, supporting unprompted learning. We also propose a unified pipeline that effectively supplies high-quality semantic information to SAM. Extensive experiments on the datasets demonstrate that the proposed PG-SAM achieves state-of-the-art performance. Our anonymous code is released at https://github.com/logan-0623/PG-SAM.

Deep reinforcement learning (DRL) has been applied in financial portfolio management to improve returns in changing market conditions. However, unlike most fields where DRL is widely used, the stock market is more volatile and dynamic as it is affected by several factors such as global events and investor sentiment. Therefore, it remains a challenge to construct a DRL-based portfolio management framework with strong return capability, stable training, and generalization ability. This study introduces a new framework utilizing the Memory Instance Gated Transformer (MIGT) for effective portfolio management. By incorporating a novel Gated Instance Attention module, which combines a transformer variant, instance normalization, and a Lite Gate Unit, our approach aims to maximize investment returns while ensuring the learning process's stability and reducing outlier impacts. Tested on the Dow Jones Industrial Average 30, our framework's performance is evaluated against fifteen other strategies using key financial metrics like the cumulative return and risk-return ratios (Sharpe, Sortino, and Omega ratios). The results highlight MIGT's advantage, showcasing at least a 9.75% improvement in cumulative returns and a minimum 2.36% increase in risk-return ratios over competing strategies, marking a significant advancement in DRL for portfolio management.

A structured understanding of intraoral 3D scans is essential for digital orthodontics. However, existing deep-learning approaches rely heavily on modality-specific training, large annotated datasets, and controlled scanning conditions, which limit generalization across devices and hinder deployment in real clinical workflows. Moreover, raw intraoral meshes exhibit substantial variation in arch pose, incomplete geometry caused by occlusion or tooth contact, and a lack of texture cues, making unified semantic interpretation highly challenging. To address these limitations, we propose ArchMap, a training-free and knowledge-guided framework for robust structured dental understanding. ArchMap first introduces a geometry-aware arch-flattening module that standardizes raw 3D meshes into spatially aligned, continuity-preserving multi-view projections. We then construct a Dental Knowledge Base (DKB) encoding hierarchical tooth ontology, dentition-stage policies, and clinical semantics to constrain the symbolic reasoning space. We validate ArchMap on 1060 pre-/post-orthodontic cases, demonstrating robust performance in tooth counting, anatomical partitioning, dentition-stage classification, and the identification of clinical conditions such as crowding, missing teeth, prosthetics, and caries. Compared with supervised pipelines and prompted VLM baselines, ArchMap achieves higher accuracy, reduced semantic drift, and superior stability under sparse or artifact-prone conditions. As a fully training-free system, ArchMap demonstrates that combining geometric normalization with ontology-guided multimodal reasoning offers a practical and scalable solution for the structured analysis of 3D intraoral scans in modern digital orthodontics.

Recent advancements in multimodal large language models (MLLMs) have significantly improved performance in visual question answering. However, they often suffer from hallucinations. In this work, hallucinations are categorized into two main types: initial hallucinations and snowball hallucinations. We argue that adequate contextual information can be extracted directly from the token interaction process. Inspired by causal inference in the decoding strategy, we propose to leverage causal masks to establish information propagation between multimodal tokens. The hypothesis is that insufficient interaction between those tokens may lead the model to rely on outlier tokens, overlooking dense and rich contextual cues. Therefore, we propose to intervene in the propagation process by tackling outlier tokens to enhance in-context inference. With this goal, we present FarSight, a versatile plug-and-play decoding strategy to reduce attention interference from outlier tokens merely by optimizing the causal mask. The heart of our method is effective token propagation. We design an attention register structure within the upper triangular matrix of the causal mask, dynamically allocating attention to capture attention diverted to outlier tokens. Moreover, a positional awareness encoding method with a diminishing masking rate is proposed, allowing the model to attend to further preceding tokens, especially for video sequence tasks. With extensive experiments, FarSight demonstrates significant hallucination-mitigating performance across different MLLMs on both image and video benchmarks, proving its effectiveness.

Tong Chen, Zimu Wang, Yiyi Miao, Haoran Luo, Sun Yuanfei, Wei Wang, Zhengyong Jiang, Procheta Sen, Jionglong Su. Proceedings of the 2025 Conference on Empirical Methods in Natural Language Processing. 2025.

Multimodal sentiment analysis (MSA) aims to understand human sentiment through multimodal data. In real-world scenarios, practical factors often lead to uncertain modality missingness. Existing methods for handling modality missingness are based on data reconstruction or common subspace projections. However, these methods neglect the confidence in multi-modal combinations and impose constraints on intra-class representation, hindering the capture of modality-specific information and resulting in suboptimal performance. To address these challenges, we propose a Confidence-Aware Self-Distillation (CASD) strategy that effectively incorporates multimodal probabilistic embeddings via a mixture of Student’s t-distributions, enhancing its robustness by incorporating confidence and accommodating heavy-tailed properties. This strategy estimates joint distributions with uncertainty scores and reduces uncertainty in the student network by consistency distillation. Furthermore, we introduce a reparameterization representation module that facilitates CASD in robust multimodal learning by sampling embeddings from the joint distribution for the prediction module to calculate the task loss. As a result, the directional constraint from the loss minimization is alleviated by the sampled representation. Experimental results on three benchmark datasets demonstrate that our method achieves state-of-the-art performance.

In endovascular surgery, the precise identification of catheters and guidewires in X-ray images is essential for reducing intervention risks. However, accurately segmenting catheter and guidewire structures is challenging due to the limited availability of labeled data. Foundation models offer a promising solution by enabling the collection of similar-domain data to train models whose weights can be fine-tuned for downstream tasks. Nonetheless, large-scale data collection for training is constrained by the necessity of maintaining patient privacy. This paper proposes a new method to train a foundation model in a decentralized federated learning setting for endovascular intervention. To ensure the feasibility of the training, we tackle the unseen data issue using differentiable Earth Mover's Distance within a knowledge distillation frame-work. Once trained, our foundation model's weights provide valuable initialization for downstream tasks, thereby enhancing task-specific performance. Intensive experiments show that our approach achieves new state-of-the-art results, contributing to advancements in endovascular intervention and robotic-assisted endovascular surgery, while addressing the critical issue of data sharing in the medical domain.

Causal mediation analysis is crucial for deconstructing complex mechanisms of action. However, in current mediation analysis, complex structures derived from causal discovery lack direct interpretation of mediation pathways, while traditional mediation analysis and effect estimation are limited by the reliance on pre-specified pathways, leading to a disconnection between structure discovery and causal mechanism understanding. Therefore, a unified framework integrating structure discovery, pathway identification, and effect estimation systematically quantifies mediation pathways under structural uncertainty, enabling automated identification and inference of mediation pathways. To this end, we propose Structure-Informed Guided Mediation Analysis (SIGMA), which guides automated mediation pathway identification through probabilistic causal structure discovery and uncertainty quantification, enabling end-to-end propagation of structural uncertainty from structure learning to effect estimation. Specifically, SIGMA employs differentiable Flow-Structural Equation Models to learn structural posteriors, generating diverse Directed Acyclic Graphs (DAGs) to quantify structural uncertainty. Based on these DAGs, we introduce the Path Stability Score to evaluate the marginal probability of pathways, identifying high-confidence mediation paths. For identified mediation pathways, we integrate Efficient Influence Functions with Bayesian model averaging to fuse within-structure estimation uncertainty and between-structure effect variation, propagating uncertainty to the final effect estimates. In synthetic data experiments, SIGMA achieves state-of-the-art performance in pathway identification accuracy and effect quantification precision under structures uncertainty, concurrent multiple pathways, and nonlinear scenarios. In real-world applications using Human Phenotype Project data, SIGMA identifies mediation effects of sleep quality on cardiovascular health through inflammatory and metabolic pathways, uncovering previously unspecified multiple mediation paths.

Zhilu Zhang, Procheta Sen, Zimu Wang, Ruoyu Sun, Zhengyong Jiang, Jionglong Su. Proceedings of the 18th Conference of the European Chapter of the Association for Computational Linguistics (Volume 1: Long Papers). 2024.

Self-supervised learning is well known for its remarkable performance in representation learning and various downstream computer vision tasks. Recently, Positive-pair-Only Contrastive Learning (POCL) has achieved reliable performance without the need to construct positive-negative training sets. It reduces memory requirements by lessening the dependency on the batch size. The POCL method typically uses a single objective function to extract the distortion invariant representation (DIR) which describes the proximity of positive-pair representations affected by different distortions. This objective function implicitly enables the model to filter out or ignore the distortion variant representation (DVR) affected by different distortions. However, some recent studies have shown that proper use of DVR in contrastive can optimize the performance of models in some downstream domain-specific tasks. In addition, these POCL methods have been observed to be sensitive to augmentation strategies. To address these limitations, we propose a novel POCL framework named Distortion-Disentangled Contrastive Learning (DDCL) and a Distortion-Disentangled Loss (DDL). Our approach is the first to explicitly and adaptively disentangle and exploit the DVR inside the model and feature stream to improve the representation utilization efficiency, robustness and representation ability. Experiments demonstrate our framework’s superiority to Barlow Twins and Simsiam in terms of convergence, representation quality (including transferability and generalization), and robustness on several datasets.

Accurate fovea localization is essential for analyzing retinal diseases to prevent irreversible vision loss. While current deep learning-based methods outperform traditional ones, they still face challenges such as the lack of local anatomical landmarks around the fovea, the inability to robustly handle diseased retinal images, and the variations in image conditions. In this paper, we propose a novel transformer-based architecture called DualStreamFoveaNet (DSFN) for multi-cue fusion. This architecture explicitly incorporates long-range connections and global features using retina and vessel distributions for robust fovea localization. We introduce a spatial attention mechanism in the dual-stream encoder to extract and fuse self-learned anatomical information, focusing more on features distributed along blood vessels and significantly reducing computational costs by decreasing token numbers. Our extensive experiments show that the proposed architecture achieves state-of-the-art performance on two public datasets and one large-scale private dataset. Furthermore, we demonstrate that the DSFN is more robust on both normal and diseased retina images and has better generalization capacity in cross-dataset experiments.

In typical data-based grasping methods, a grasp based on parallel-jaw grippers is parameterized by the center of the gripper, the rotation angle, and the gripper opening width so as to predict the quality and pose of grasps at every pixel. In contrast, a grasp is represented using only two contact points for contact-points-based grasp representation, which allows for fusion with tactile sensors more naturally. In this work, we propose a method using contact-points-based grasp representation to get a robust grasp using only one contact points quality map generated by a neural network, which significantly reduces the complexity of the network with fewer parameters. We provide a synthetic dataset including depth image and contact points quality map generated by thousands of 3D models. We also provide the method for data generation, which can be used for contact-points-based multi-fingers grasp. Experiments show that contact points quality network can plan an available grasp in 0.15 seconds. The grasping success rate for unknown household objects is 94%. Our method is also available for deformable objects with a success rate of 95%. The dataset and reference code can be found on the project website: https://sites.google.com/view/cpqnet.

Motivation N6-methyladenosine (m6A) is the most prevalent RNA modification on mRNAs and lncRNAs. Evidence increasingly demonstrates its crucial importance in essential molecular mechanisms and various diseases. With recent advances in sequencing techniques, tens of thousands of m6A sites are identified in a typical high-throughput experiment, posing a key challenge to distinguish the functional m6A sites from the remaining 'passenger' (or 'silent') sites. Results: We performed a comparative conservation analysis of the human and mouse m6A epitranscriptomes at single site resolution. A novel scoring framework, ConsRM, was devised to quantitatively measure the degree of conservation of individual m6A sites. ConsRM integrates multiple information sources and a positive-unlabeled learning framework, which integrated genomic and sequence features to trace subtle hints of epitranscriptome layer conservation. With a series validation experiments in mouse, fly and zebrafish, we showed that ConsRM outperformed well-adopted conservation scores (phastCons and phyloP) in distinguishing the conserved and unconserved m6A sites. Additionally, the m6A sites with a higher ConsRM score are more likely to be functionally important. An online database was developed containing the conservation metrics of 177 998 distinct human m6A sites to support conservation analysis and functional prioritization of individual m6A sites. And it is freely accessible at: https://www.xjtlu.edu.cn/biologicalsciences/con.

MOTIVATION: Increasing evidence suggests that post-transcriptional ribonucleic acid (RNA) modifications regulate essential biomolecular functions and are related to the pathogenesis of various diseases. Precise identification of RNA modification sites is essential for understanding the regulatory mechanisms of RNAs. To date, many computational approaches for predicting RNA modifications have been developed, most of which were based on strong supervision enabled by base-resolution epitranscriptome data. However, high-resolution data may not be available. RESULTS: We propose WeakRM, the first weakly supervised learning framework for predicting RNA modifications from low-resolution epitranscriptome datasets, such as those generated from acRIP-seq and hMeRIP-seq. Evaluations on three independent datasets (corresponding to three different RNA modification types and their respective sequencing technologies) demonstrated the effectiveness of our approach in predicting RNA modifications from low-resolution data. WeakRM outperformed state-of-the-art multi-instance learning methods for genomic sequences, such as WSCNN, which was originally designed for transcription factor binding site prediction. Additionally, our approach captured motifs that are consistent with existing knowledge, and visualization of the predicted modification-containing regions unveiled the potentials of detecting RNA modifications with improved resolution. AVAILABILITY IMPLEMENTATION: The source code for the WeakRM algorithm, along with the datasets used, are freely accessible at: https://github.com/daiyun02211/WeakRM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: The distribution of biological features strongly indicates their functional relevance. Compared to DNA-related features, deciphering the distribution of mRNA-related features is non-trivial due to the existence of isoform ambiguity and compositional diversity of mRNAs. RESULTS: We propose here a rigorous statistical framework, MetaTX, for deciphering the distribution of mRNA-related features. Through a standardized mRNA model, MetaTX firstly unifies various mRNA transcripts of diverse compositions, and then corrects the isoform ambiguity by incorporating the overall distribution pattern of the features through an EM algorithm. MetaTX was tested on both simulated and real data. Results suggested that MetaTX substantially outperformed existing direct methods on simulated datasets, and that a more informative distribution pattern was produced for all the three datasets tested, which contain N6-Methyladenosine sites generated by different technologies. MetaTX should make a useful tool for studying the distribution and functions of mRNA-related biological features, especially for mRNA modifications such as N6-Methyladenosine. AVAILABILITY AND IMPLEMENTATION: The MetaTX R package is freely available at GitHub: https://github.com/yue-wang-biomath/MetaTX.1.0. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Recent progress in N7-methylguanosine (m7G) RNA methylation studies has focused on its internal (rather than capped) presence within mRNAs. Tens of thousands of internal mRNA m7G sites have been identified within mammalian transcriptomes, and a single resource to best share, annotate and analyze the massive m7G data generated recently are sorely needed. RESULTS: We report here m7GHub, a comprehensive online platform for deciphering the location, regulation and pathogenesis of internal mRNA m7G. The m7GHub consists of four main components, including: the first internal mRNA m7G database containing 44 058 experimentally validated internal mRNA m7G sites, a sequence-based high-accuracy predictor, the first web server for assessing the impact of mutations on m7G status, and the first database recording 1218 disease-associated genetic mutations that may function through regulation of m7G methylation. Together, m7GHub will serve as a useful resource for research on internal mRNA m7G modification. AVAILABILITY AND IMPLEMENTATION: m7GHub is freely accessible online at www.xjtlu.edu.cn/biologicalsciences/m7ghub. CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Ye Ma, Lu Zong, Yikang Yang, Jionglong Su. Proceedings of the 2019 Conference on Empirical Methods in Natural Language Processing and the 9th International Joint Conference on Natural Language Processing (EMNLP-IJCNLP). 2019.

Over one hundred different types of post-transcriptional RNA modifications have been identified in human. Researchers discovered that RNA modifications can regulate various biological processes, and RNA methylation, especially N6-methyladenosine, has become one of the most researched topics in epigenetics. To date, the study of epitranscriptome layer gene regulation is mostly focused on the function of mediator proteins of RNA methylation, i.e., the readers, writers and erasers. There is limited investigation of the functional relevance of individual m6A RNA methylation site. To address this, we annotated human m6A sites in large-scale based on the guilt-by-association principle from an RNA co-methylation network. It is constructed based on public human MeRIP-Seq datasets profiling the m6A epitranscriptome under 32 independent experimental conditions. By systematically examining the network characteristics obtained from the RNA methylation profiles, a total of 339,158 putative gene ontology functions associated with 1446 human m6A sites were identified. These are biological functions that may be regulated at epitranscriptome layer via reversible m6A RNA methylation. The results were further validated on a soft benchmark by comparing to a random predictor. An online web server m6Acomet was constructed to support direct query for the predicted biological functions of m6A sites as well as the sites exhibiting co-methylated patterns at the epitranscriptome layer. The m6Acomet web server is freely available at: www.xjtlu.edu.cn/biologicalsciences/m6acomet .