Existing paper review methods often rely on superficial manuscript features or directly on large language models (LLMs), which are prone to hallucinations, biased scoring, and limited reasoning capabilities. Moreover, these methods often fail to capture the complex argumentative reasoning and negotiation dynamics inherent in reviewer-author interactions. To address these limitations, we propose ReViewGraph (Reviewer-Author Debates Graph Reasoner), a novel framework that performs heterogeneous graph reasoning over LLM-simulated multi-round reviewer-author debates. In our approach, reviewer-author exchanges are simulated through LLM-based multi-agent collaboration. Diverse opinion relations (e.g., acceptance, rejection, clarification, and compromise) are then explicitly extracted and encoded as typed edges within a heterogeneous interaction graph. By applying graph neural networks to reason over these structured debate graphs, ReViewGraph captures fine-grained argumentative dynamics and enables more informed review decisions. Extensive experiments on three datasets demonstrate that ReViewGraph outperforms strong baselines with an average relative improvement of 15.73%, underscoring the value of modeling detailed reviewer–author debate structures.

Feiteng Fang, Dingwei Chen, Xiang Huang, Ting-En Lin, Yuchuan Wu, Xiong Liu, Jing Ye, Ziqiang Liu, Haonan Zhang, Liang Zhu, Hamid Alinejad-Rokny, Min Yang, Yongbin Li. Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers). 2026.

E-commerce platforms increasingly rely on Large Language Models (LLMs) and Vision Language Models (VLMs) to detect illicit or misleading product content. However, these models remain vulnerable to evasive content, which refers to inputs that have been deliberately modified through techniques such as word splitting, euphemistic language, or image cropping to conceal policy violations while still conveying prohibited claims. Crucially, detecting such content requires a model to simultaneously master two capabilities: accurately comprehending complex rules, and correctly inferring the true intent behind deliberately obfuscated multimodal inputs. While prior work has separately explored LLM reasoning over complex rules and LLM-based detection of evasive content, no existing benchmark combines both within a unified evaluation framework. This gap is particularly consequential in e-commerce, where accurate moderation demands that both capabilities operate in concert. To address this gap, we introduce EVADE-Bench, the first expert-curated Chinese multimodal benchmark specifically designed to evaluate LLMs and VLMs on evasive content detection in real-world e-commerce scenarios. The dataset contains 2,833 annotated text samples and 13,961 annotated images spanning six violation categories. Our comprehensive evaluation of 26 open- and closed-source LLMs and VLMs reveals that even state-of-the-art models frequently misclassify evasive samples. We further demonstrate that clearer rule categorization significantly improves model prediction consistency and reduces false predictions, highlighting the critical role of benchmark design in enabling reliable evaluation. We analyze common error patterns across these models and identify systematic limitations in their ability to reason over metaphorical expressions and complex regulatory rules. To explore paths for performance improvement, we investigate the feasibility of multi-agent decomposition for multimodal reasoning, wherein visual description and logical inference are decoupled into separate agents, and find that this strategy yields notable accuracy gains. By releasing EVADE-Bench, we provide the first rigorous standard for evaluating evasive content detection and aim to support the development of safer and more trustworthy content moderation systems. The dataset is publicly available at https://huggingface.co/datasets/koenshen/EVADE-Bench.

MOTIVATION: The American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines represent the gold standard for clinical variant interpretation. Despite the widespread adoption of ACMG/AMP guidelines, a comprehensive comparison of the software tools designed to implement them has been lacking. This represents a significant gap, as clinicians require evidence-based guidance on which tools to use in their practice. RESULTS: We benchmarked four ACMG/AMP-based tools (Franklin, InterVar, TAPES, Genebe) selected from 22 tools, and compared their performance with LIRICAL, a top-performing phenotype-driven tool, using 151 expert-curated datasets from Mendelian disorders. Selection criteria included free availability, VCF compatibility, operational reliability, and not being disease-specific. Our evaluation framework assessed top-N accuracy (N = 1, 5, 10, 20, 50), retention rates, precision, recall, F1 scores, and area under the curve (AUC). Statistical validation employed bootstrap confidence intervals (n = 1000) and Friedman tests. LIRICAL (68.21%) and Franklin (61.59%) demonstrated superior top-10 variant prioritization accuracy in Mendelian disorders, significantly outperforming other tools (P = .0000). Results demonstrate that tools with advanced phenotypic integration significantly outperform those relying primarily on genomic features. AVAILABILITY AND IMPLEMENTATION: All data and source code required to reproduce the findings of this study are openly available in the Code Ocean repository at https://doi.org/10.24433/CO.6562438.v1.

Object recognition is essential for autonomous cars, and the amalgamation of camera and light detection and ranging (LiDAR) sensor data has emerged as a pivotal method for accurate three-dimensional (3D) object recognition. Contemporary algorithms face challenges with fragmented data, high processing costs, insufficient resolution, and limited dynamic information. This study presents a novel approach utilising 3D U-Net deep learning for precise 3D object detection and localisation by integrating camera and LiDAR data. The process involves obtaining and preprocessing camera and LiDAR data, utilising a geometric 3D frustum method to extract 3D information from LiDAR based on 2D camera bounding boxes, and training a You Only Look Once version 4 (YOLO v4) network to recognise these boundaries in camera images. The detected images are combined with LiDAR data, and a deep U-Net network is utilised to define 3D bounding boxes. Performance is assessed at various noise levels (0 %, 1 %, 2 %, 5 %, and 10 %) in the composite images. This method leverages the benefits of both sensors to better object recognition across diverse shapes and sizes, even in challenging situations, signifying a significant progression towards safer and more reliable autonomous vehicles with improved situational awareness in intricate urban environments.

Computational complexity of Bayesian learning is impeding its adoption in practical, large-scale tasks, despite demonstrations of significant merits such as improved robustness and resilience to unseen or out-of-distribution inputs over their non-Bayesian counterparts. Although, Deep ensemble methods (Seligmann et al. 2024; Lakshminarayanan, Pritzel, and Blundell 2017) have proven to be highly effective for Bayesian deep learning, their practical application is hindered by substantial computational cost. In this study, we introduce an innovative framework to mitigate the computational burden of ensemble Bayesian deep learning. We explore a more feasible alternative, inspired by the recent success of low-rank adapters, we introduce Bayesian Low-Rank LeArning (Bella). We show, i) Bella achieves a dramatic reduction in the number of trainable parameters required to approximate a Bayesian posterior; and ii) it not only maintains, but in some instances, surpasses the performance–in accuracy and out-of-distribution generalisation–of conventional Bayesian learning methods and non-Bayesian baselines. Our extensive empirical evaluation in large-scale tasks such as ImageNet, CAMELYON17, DomainNet, VQA with CLIP, LLaVA demonstrate the effectiveness and versatility of Bella in building highly scalable and practical Bayesian deep models for real-world applications.

Longze Chen, Renke Shan, Huiming Wang, Lu Wang, Ziqiang Liu, Run Luo, Jiawei Wang, Hamid Alinejad-Rokny, Min Yang. Proceedings of the 63rd Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers). 2025.

Sunbowen Lee, Junting Zhou, Chang Ao, Kaige Li, Xeron Du, Sirui He, Haihong Wu, Tianci Liu, Jiaheng Liu, Hamid Alinejad-Rokny, Min Yang, Yitao Liang, Zhoufutu Wen, Shiwen Ni. Proceedings of the 63rd Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers). 2025.

Yang Sun, Guanrong Chen, Hamid Alinejad-Rokny, Jianzhu Bao, Yuqi Huang, Bin Liang, Kam-Fai Wong, Min Yang, Ruifeng Xu. Proceedings of the 63rd Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers). 2025.

Numerous medical systems powered by Large Language Models (LLMs) have achieved substantial progress, enabling them to perform diverse healthcare tasks. However, existing research is limited by the absence of real-world datasets specifically addressing medication safety, primarily due to privacy regulations and data accessibility challenges. Moreover, the evaluation of LLM-based systems in realistic clinical consultation settings, particularly with respect to medication safety, remains underexplored. To bridge these gaps, we propose a novel frame-work to simulate and evaluate clinical consultation scenarios for systematically assessing the medication safety capabilities of LLMs. Within this framework, we generate inquiry-diagnosis dialogues embedded with relevant medication risks and construct a dedicated medication safety database, RxRisk DB, comprising 6,725 contraindications, 28,781 drug interactions, and 14,906 indication-drug pairs. A two-stage filtering strategy ensures clinical realism and professional quality, resulting in the final benchmark, RxSafeBench, which includes 2,443 high-quality consultation scenarios evenly split across contraindication and interaction types. We evaluate state-of-the-art open-source and proprietary LLMs using a structured multiple-choice format that tests the models' ability to recommend the most appropriate medication given simulated patient context. Results reveal that current LLMs struggle to reliably incorporate contraindication and drug interaction information, especially when risks are implied rather than explicitly stated. Our findings highlight key challenges in deploying LLMs for medication safety and offer insights into improving their reliability through enhanced prompting strategies and task-specific fine-tuning. By introducing RxSafeBench, we provide the first comprehensive benchmark for assessing medication safety in LLMs, paving the way toward safer and more trustworthy AI-driven clinical decision support systems. Our code and data are released at https://github.com/CAS-SIAT-XinHai/RxSafeBench.

Dingwei Chen, Ziqiang Liu, Feiteng Fang, Chak Tou Leong, Shiwen Ni, Ahmadreza Argha, Hamid Alinejad-Rokny, Min Yang, Chengming Li. Proceedings of the 2025 Conference on Empirical Methods in Natural Language Processing. 2025.

The development of large language models (LLMs) has significantly advanced the emergence of large multimodal models (LMMs). While LMMs have achieved tremendous success by promoting the synergy between multimodal comprehension and creation, they often face challenges when confronted with out-of-distribution data, such as which can hardly distinguish orientation, quantity, color, structure, etc. This is primarily due to their reliance on image encoders trained to encode images into task-relevant features, which may lead them to disregard irrelevant details. Delving into the modeling capabilities of diffusion models for images naturally prompts the question: Can diffusion models serve as the eyes of large language models for image perception? In this paper, we propose DEEM, a simple but effective approach that utilizes the generative feedback of diffusion models to align the semantic distributions of the image encoder. This addresses the drawbacks of previous methods that solely relied on image encoders like CLIP-ViT, thereby enhancing the model's resilience against out-of-distribution samples and reducing visual hallucinations. Importantly, this is achieved without requiring additional training modules and with fewer training parameters. We extensively evaluated DEEM on both our newly constructed RobustVQA benchmark and other well-known benchmarks, POPE and MMVP, for visual hallucination and perception. In particular, DEEM improves LMM's visual perception performance to a large extent (e.g., 4\% ↑ on RobustVQA, 6.5\% ↑ on MMVP and 12.8 \% ↑ on POPE ). Compared to the state-of-the-art interleaved content generation models, DEEM exhibits enhanced robustness and a superior capacity to alleviate model hallucinations while utilizing fewer trainable parameters, less pre-training data (10\%), and a smaller base model size. Extensive experiments demonstrate that DEEM enhances the performance of LMMs on various downstream tasks without inferior performance in the long term, including visual question answering, image captioning, and text-conditioned image synthesis.

Recent advancements in omnimodal learning have significantly improved understanding and generation across images, text, and speech, yet these developments remain predominantly confined to proprietary models. The lack of high-quality omnimodal datasets and the challenges of real-time emotional speech synthesis have notably hindered progress in open-source research. To address these limitations, we introduce OpenOmni, a two-stage training framework that integrates omnimodal alignment and speech generation to develop a state-of-the-art omnimodal large language model. In the alignment phase, a pretrained speech model undergoes further training on image-text tasks, enabling (near) zero-shot generalization from vision to speech, outperforming models trained on tri-modal datasets. In the speech generation phase, a lightweight decoder is trained on speech tasks with direct preference optimization, which enables real-time emotional speech synthesis with high fidelity. Extensive experiments demonstrate that OpenOmni surpasses state-of-the-art models across omnimodal, vision-language, and speech-language benchmarks. It achieves a 4-point absolute improvement on OmniBench over the leading open-source model VITA, despite using 5$\times$ fewer training examples and a smaller model size (7B vs. 7$\times$8B). Besides, OpenOmni achieves real-time speech generation with less than 1 second latency at non-autoregressive mode, reducing inference time by 5$\times$ compared to autoregressive methods, and improves emotion classification accuracy by 7.7\%. The codebase is available at https://github.com/RainBowLuoCS/OpenOmni.

Test time adaptation (TTA) equips deep learning models to handle unseen test data that deviates from the training distribution, even when source data is inaccessible. While traditional TTA methods often rely on entropy as a confidence metric, its effectiveness can be limited, particularly in biased scenarios. Extending existing approaches like the Pseudo Label Probability Difference (PLPD), we introduce ETAGE, a refined TTA method that integrates entropy minimization with gradient norms and PLPD, to enhance sample selection and adaptation. Our method prioritizes samples that are less likely to cause instability by combining high entropy with high gradient norms out of adaptation, thus avoiding the overfitting to noise often observed in previous methods. Extensive experiments on CIFAR-10-C and CIFAR-100-C datasets demonstrate that our approach outperforms existing TTA techniques, particularly in challenging and biased scenarios, leading to more robust and consistent model performance across diverse test scenarios. The codebase for ETAGE is available on https://github.com/afsharshamsi/ETAGE.

Casting defects pose a significant challenge in the manufacturing industry, leading to material waste, production inefficiencies, and compromised product quality. While deep learning models have shown promise in automating defect detection, their effectiveness is often constrained by domain shifts and variability in real-world data distributions. In this work, we propose Bayesian Test-Time Adaptation (BTTA), a novel framework designed to enhance the robustness and adaptability of machine learning models in such dynamic environments. Unlike traditional Test-Time Adaptation (TTA) methods, our approach employs gradient-guided diversification with Stein Variational Gradient Descent (SVGD) to explore diverse optimization paths. Experimental results on benchmark datasets, including CIFAR-10-C , Casting Defects , and GDXray , demonstrate significant performance improvements across key metrics. Notably, the framework achieves an average accuracy improvement of 2-3% under severe corruption levels and excels in cross-domain generalization, highlighting its ability to handle diverse and unseen defect categories. This dynamic adaptability not only addresses the limitations of static models but also offers a practical and cost-effective solution for real-time defect detection in industrial settings. Our study underscores the potential of BTTA to transform quality assurance processes, ensuring reliable performance across varying operational conditions without the need for extensive retraining or large annotated datasets. The codebase for BTTA is available on: https://github.com/afsharshamsi/GradSurgery .

Spatially resolved transcriptomics (SRT) is a pioneering method for simultaneously studying morphological contexts and gene expression at single-cell precision. Data emerging from SRT are multifaceted, presenting researchers with intricate gene expression matrices, precise spatial details and comprehensive histology visuals. Such rich and intricate datasets, unfortunately, render many conventional methods like traditional machine learning and statistical models ineffective. The unique challenges posed by the specialized nature of SRT data have led the scientific community to explore more sophisticated analytical avenues. Recent trends indicate an increasing reliance on deep learning algorithms, especially in areas such as spatial clustering, identification of spatially variable genes and data alignment tasks. In this manuscript, we provide a rigorous critique of these advanced deep learning methodologies, probing into their merits, limitations and avenues for further refinement. Our in-depth analysis underscores that while the recent innovations in deep learning tailored for SRT have been promising, there remains a substantial potential for enhancement. A crucial area that demands attention is the development of models that can incorporate intricate biological nuances, such as phylogeny-aware processing or in-depth analysis of minuscule histology image segments. Furthermore, addressing challenges like the elimination of batch effects, perfecting data normalization techniques and countering the overdispersion and zero inflation patterns seen in gene expression is pivotal. To support the broader scientific community in their SRT endeavors, we have meticulously assembled a comprehensive directory of readily accessible SRT databases, hoping to serve as a foundation for future research initiatives.

BACKGROUND: Copy number variants (CNVs) have become increasingly instrumental in understanding the etiology of all diseases and phenotypes, including Neurocognitive Disorders (NDs). Among the well-established regions associated with ND are small parts of chromosome 16 deletions (16p11.2) and chromosome 15 duplications (15q3). Various methods have been developed to identify associations between CNVs and diseases of interest. The majority of methods are based on statistical inference techniques. However, due to the multi-dimensional nature of the features of the CNVs, these methods are still immature. The other aspect is that regions discovered by different methods are large, while the causative regions may be much smaller. RESULTS: In this study, we propose a regularized deep learning model to select causal regions for the target disease. With the help of the proximal [20] gradient descent algorithm, the model utilizes the group LASSO concept and embraces a deep learning model in a sparsity framework. We perform the CNV analysis for 74,811 individuals with three types of brain disorders, autism spectrum disorder (ASD), schizophrenia (SCZ), and developmental delay (DD), and also perform cumulative analysis to discover the regions that are common among the NDs. The brain expression of genes associated with diseases has increased by an average of 20 percent, and genes with homologs in mice that cause nervous system phenotypes have increased by 18 percent (on average). The DECIPHER data source also seeks other phenotypes connected to the detected regions alongside gene ontology analysis. The target diseases are correlated with some unexplored regions, such as deletions on 1q21.1 and 1q21.2 (for ASD), deletions on 20q12 (for SCZ), and duplications on 8p23.3 (for DD). Furthermore, our method is compared with other machine learning algorithms. CONCLUSIONS: Our model effectively identifies regions associated with phenotypic traits using regularized deep learning. Rather than attempting to analyze the whole genome, CNVDeep allows us to focus only on the causative regions of disease.

Unsupervised spike sorting, a vital processing step in real-time brain-implantable microsystems, is faced with the prominent challenge of managing nonstationarity in neural signals. In long-term recordings, spike waveforms gradually change and new source neurons are likely to become activated. Adaptive spike sorters combined with on-implant training units effectively process the nonstationary signals at the cost of high hardware resource utilization. On the other hand, static approaches, while being hardware-friendly, are subjected to decreased processing performance in such recordings where the neural signal characteristics gradually change. To strike a balance between the hardware cost and processing performance, this study proposes a hardware-efficient novelty-aware spike sorting approach that is capable of dealing with both variated spike waveforms and spike waveforms generated from new source neurons. Its improved hardware efficiency compared to adaptive ones and capability of dealing with nonstationary signals make it attractive for implantable applications. The proposed novelty-aware spike sorting especially would be a good fit for brain–computer interfaces where long-term, real-time interaction with the brain is required, and the available on-implant hardware resources are limited. Our unsupervised spike sorting benefits from a novelty detection process to deal with neural signal variations. It tracks the spike features so that in case of detecting an unexpected change (novelty detection) both on and off-implant parameters are updated to preserve the performance in new state. To make the proposed approach agile enough to be suitable for brain implants, the on-implant computations are reduced while the computational burden is realized off-implant. The performance of our proposed approach is evaluated using both synthetic and real datasets. The results demonstrate that, in the mean, it is capable of detecting 94.31% of novel spikes (wave-drifted or emerged spikes) with a classification accuracy (CA) of 96.31%. Moreover, an FPGA prototype of the on-implant circuit is implemented and tested. It is shown that in comparison to the OSORT algorithm, a pivotal spike sorting method, our spike sorting provides a higher CA at significantly lower hardware resources. The proposed circuit is also implemented in a 180-nm standard CMOS process, achieving a power consumption of 1.78[Formula: see text][Formula: see text] per channel and a chip area of 0.07[Formula: see text]mm2 per channel.

Alzheimer's is progressive and irreversible type of dementia, which causes degeneration and death of cells and their connections in the brain. AD worsens over time and greatly impacts patients' life and affects their important mental functions, including thinking, the ability to carry on a conversation, and judgment and response to environment. Clinically, there is no single test to effectively diagnose Alzheimer disease. However, computed tomography (CT) and magnetic resonance imaging (MRI) scans can be used to help in AD diagnosis by observing critical changes in the size of different brain areas, typically parietal and temporal lobes areas. In this work, an integrative mulitresolutional ensemble deep learning-based framework is proposed to achieve better predictive performance for the diagnosis of Alzheimer disease. Unlike ResNet, DenseNet and their variants proposed pipeline utilizes PartialNet in a hierarchical design tailored to AD detection using brain MRIs. The advantage of the proposed analysis system is that PartialNet diversified the depth and deep supervision. Additionally, it also incorporates the properties of identity mappings which makes it powerful in better learning due to feature reuse. Besides, the proposed ensemble PartialNet is better in vanishing gradient, diminishing forward-flow with low number of parameters and better training time in comparison to its counter network. The proposed analysis pipeline has been tested and evaluated on benchmark ADNI dataset collected from 379 subjects patients. Quantitative validation of the obtained results documented our framework's capability, outperforming state-of-the-art learning approaches for both multi-and binary-class AD detection.

Development of advance surface Electromyogram (sEMG)-based Human-Machine Interface (HMI) systems is of paramount importance to pave the way towards emergence of futuristic Cyber-Physical-Human (CPH) worlds. In this context, the main focus of recent literature was on development of different Deep Neural Network (DNN)-based architectures that perform Hand Gesture Recognition (HGR) at a macroscopic level (i.e., directly from sEMG signals). At the same time, advancements in acquisition of High-Density sEMG signals (HD-sEMG) have resulted in a surge of significant interest on sEMG decomposition techniques to extract microscopic neural drive information. However, due to complexities of sEMG decomposition and added computational overhead, HGR at microscopic level is less explored than its aforementioned macroscopic-level, DNN-based counterparts. In this regard, we propose the HYDRA-HGR framework, which is a hybrid model for HGR that simultaneously extracts a set of temporal and spatial features through its two independent Vision Transformer (ViT)-based parallel architectures (the so called Macro and Micro paths). The Macro Path is trained directly on the pre-processed HD-sEMG signals, while the Micro path is fed with the p-to-p values of the extracted Motor Unit Action Potentials (MUAPs) of each source. Extracted features at macroscopic and microscopic levels are then coupled via a Fully Connected (FC) fusion layer for final gesture classification. We evaluate the proposed hybrid HYDRA-HGR framework through a recently released HD-sEMG dataset, and show that it significantly outperforms its stand-alone counterparts. The proposed HYDRA-HGR framework achieves average accuracy of 94.86% for the 250 ms window size, which is 5.52 % and 8.22 % higher than that of the Macro and Micro paths, respectively.

Abstract Skin cancer, primarily resulting from the abnormal growth of skin cells, is among the most common cancer types. In recent decades, the incidence of skin cancer cases worldwide has risen significantly (one in every three newly diagnosed cancer cases is a skin cancer). Such an increase can be attributed to changes in our social and lifestyle habits coupled with devastating man-made alterations to the global ecosystem. Despite such a notable increase, diagnosis of skin cancer is still challenging, which becomes critical as its early detection is crucial for increasing the overall survival rate. This calls for advancements of innovative computer-aided systems to assist medical experts with their decision making. In this context, there has been a recent surge of interest in machine learning (ML), in particular, deep neural networks (DNNs), to provide complementary assistance to expert physicians. While DNNs have a high processing capacity far beyond that of human experts, their outputs are deterministic, i.e., providing estimates without prediction confidence. Therefore, it is of paramount importance to develop DNNs with uncertainty-awareness to provide confidence in their predictions. Monte Carlo dropout (MCD) is vastly used for uncertainty quantification; however, MCD suffers from overconfidence and being miss calibrated. In this paper, we use MCD algorithm to develop an uncertainty-aware DNN that assigns high predictive entropy to erroneous predictions and enable the model to optimize the hyper-parameters during training, which leads to more accurate uncertainty quantification. We use two synthetic (two moons and blobs) and a real dataset (skin cancer) to validate our algorithm. Our experiments on these datasets prove effectiveness of our approach in quantifying reliable uncertainty. Our method achieved 85.65 ± 0.18 prediction accuracy, 83.03 ± 0.25 uncertainty accuracy, and 1.93 ± 0.3 expected calibration error outperforming vanilla MCD and MCD with loss enhanced based on predicted entropy.

The genetic etiology of brain disorders is highly heterogeneous, characterized by abnormalities in the development of the central nervous system that lead to diminished physical or intellectual capabilities. The process of determining which gene drives disease, known as "gene prioritization," is not entirely understood. Genome-wide searches for gene-disease associations are still underdeveloped due to reliance on previous discoveries and evidence sources with false positive or negative relations. This paper introduces DeepGenePrior, a model based on deep neural networks that prioritizes candidate genes in genetic diseases. Using the well-studied Variational AutoEncoder (VAE), we developed a score to measure the impact of genes on target diseases. Unlike other methods that use prior data to select candidate genes, based on the "guilt by association" principle and auxiliary data sources like protein networks, our study exclusively employs copy number variants (CNVs) for gene prioritization. By analyzing CNVs from 74,811 individuals with autism, schizophrenia, and developmental delay, we identified genes that best distinguish cases from controls. Our findings indicate a 12% increase in fold enrichment in brain-expressed genes compared to previous studies and a 15% increase in genes associated with mouse nervous system phenotypes. Furthermore, we identified common deletions in ZDHHC8, DGCR5, and CATG00000022283 among the top genes related to all three disorders, suggesting a common etiology among these clinically distinct conditions. DeepGenePrior is publicly available online at http://git.dml.ir/z_rahaie/DGP to address obstacles in existing gene prioritization studies identifying candidate genes.

Mental health disorders may cause severe consequences for countries’ economies and health. Identifying early signs of these disorders is vital. The state-of-the-art research in identifying mental health disorder patterns from textual data, uses hand-labeled training sets, especially when a domain expert’s knowledge is required to analyze various symptoms in a patient. This task could be time-consuming and expensive. To address this challenge, in this paper, we study and analyze the various clinical and non-clinical approaches to identifying mental health disorders. We leverage the domain knowledge and expertise in cognitive science to build a domain-specific Knowledge Base for the mental health disorder concepts and patterns. We present a weaker form of supervision by facilitating and generating training data from a domain-specific Knowledge Base. We adopt a typical scenario for analyzing social media to identify depression symptoms from the textual content generated by social users.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Recent studies have observed causative mutations in susceptible genes related to colorectal cancer in 10 to 15% of the patients. This highlights the importance of identifying mutations for early detection of this cancer for more effective treatments among high risk individuals. Mutation is considered as the key point in cancer research. Many studies have performed cancer subtyping based on the type of frequently mutated genes, or the proportion of mutational processes. However, to the best of our knowledge, combination of these features has never been used together for this task. This highlights the potential to introduce better and more inclusive subtype classification approaches using wider range of related features to enable biomarker discovery and thus inform drug development for CRC. RESULTS: In this study, we develop a new pipeline based on a novel concept called 'gene-motif', which merges mutated gene information with tri-nucleotide motif of mutated sites, for colorectal cancer subtype identification. We apply our pipeline to the International Cancer Genome Consortium (ICGC) CRC samples and identify, for the first time, 3131 gene-motif combinations that are significantly mutated in 536 ICGC colorectal cancer samples. Using these features, we identify seven CRC subtypes with distinguishable phenotypes and biomarkers, including unique cancer related signaling pathways, in which for most of them targeted treatment options are currently available. Interestingly, we also identify several genes that are mutated in multiple subtypes but with unique sequence contexts. CONCLUSION: Our results highlight the importance of considering both the mutation type and mutated genes in identification of cancer subtypes and cancer biomarkers. The new CRC subtypes presented in this study demonstrates distinguished phenotypic properties which can be effectively used to develop new treatments. By knowing the genes and phenotypes associated with the subtypes, a personalized treatment plan can be developed that considers the specific phenotypes associated with their genomic lesion.

BACKGROUND: The advent of high throughput sequencing has enabled researchers to systematically evaluate the genetic variations in cancer, identifying many cancer-associated genes. Although cancers in the same tissue are widely categorized in the same group, they demonstrate many differences concerning their mutational profiles. Hence, there is no definitive treatment for most cancer types. This reveals the importance of developing new pipelines to identify cancer-associated genes accurately and re-classify patients with similar mutational profiles. Classification of cancer patients with similar mutational profiles may help discover subtypes of cancer patients who might benefit from specific treatment types. RESULTS: In this study, we propose a new machine learning pipeline to identify protein-coding genes mutated in many samples to identify cancer subtypes. We apply our pipeline to 12,270 samples collected from the international cancer genome consortium, covering 19 cancer types. As a result, we identify 17 different cancer subtypes. Comprehensive phenotypic and genotypic analysis indicates distinguishable properties, including unique cancer-related signaling pathways. CONCLUSIONS: This new subtyping approach offers a novel opportunity for cancer drug development based on the mutational profile of patients. Additionally, we analyze the mutational signatures for samples in each subtype, which provides important insight into their active molecular mechanisms. Some of the pathways we identified in most subtypes, including the cell cycle and the Axon guidance pathways, are frequently observed in cancer disease. Interestingly, we also identified several mutated genes and different rates of mutation in multiple cancer subtypes. In addition, our study on "gene-motif" suggests the importance of considering both the context of the mutations and mutational processes in identifying cancer-associated genes. The source codes for our proposed clustering pipeline and analysis are publicly available at: https://github.com/bcb-sut/Pan-Cancer .

Hi-C is a genome-wide chromosome conformation capture technology that detects interactions between pairs of genomic regions and exploits higher order chromatin structures. Conceptually Hi-C data counts interaction frequencies between every position in the genome and every other position. Biologically functional interactions are expected to occur more frequently than transient background and artefactual interactions. To identify biologically relevant interactions, several background models that take biases such as distance, GC content and mappability into account have been proposed. Here we introduce MaxHiC, a background correction tool that deals with these complex biases and robustly identifies statistically significant interactions in both Hi-C and capture Hi-C experiments. MaxHiC uses a negative binomial distribution model and a maximum likelihood technique to correct biases in both Hi-C and capture Hi-C libraries. We systematically benchmark MaxHiC against major Hi-C background correction tools including Hi-C significant interaction callers (SIC) and Hi-C loop callers using published Hi-C, capture Hi-C, and Micro-C datasets. Our results demonstrate that 1) Interacting regions identified by MaxHiC have significantly greater levels of overlap with known regulatory features (e.g. active chromatin histone marks, CTCF binding sites, DNase sensitivity) and also disease-associated genome-wide association SNPs than those identified by currently existing models, 2) the pairs of interacting regions are more likely to be linked by eQTL pairs and 3) more likely to link known regulatory features including known functional enhancer-promoter pairs validated by CRISPRi than any of the existing methods. We also demonstrate that interactions between different genomic region types have distinct distance distributions only revealed by MaxHiC. MaxHiC is publicly available as a python package for the analysis of Hi-C, capture Hi-C and Micro-C data.

[This corrects the article DOI: 10.1371/journal.pcbi.1010241.].

MOTIVATION: CircRNAs are covalently closed RNA molecules that are particularly abundant in the brain. While circRNA expression data from the human brain is rapidly accumulating, integration of large-scale datasets remains challenging and time-consuming, and consequently an integrative view of circRNA expression in the human brain is currently lacking. RESULTS: NeuroCirc is a web-based resource that allows interactive exploration of multiple types of circRNA data from the human brain, including large-scale expression datasets, circQTL data and circRNA expression across neuronal differentiation and cellular maturation time-courses. NeuroCirc also allows users to upload their own circRNA expression data and explore it in the integrative platform, thereby supporting circRNA prioritization for experimental validation and functional studies. AVAILABILITY AND IMPLEMENTATION: NeuroCirc is freely available at: https://voineagulab.github.io/NeuroCirc/. The source code and user documentation are available at: https://github.com/Voineagulab/NeuroCirc. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Different classifiers with different characteristics and methodologies can complement each other and cover their internal weaknesses; so classifier ensemble is an important approach to handle the weakness of single classifier based systems. In this article we explore an automatic and fast function to approximate the accuracy of a given classifier on a typical dataset. Then employing the function, we can convert the ensemble learning to an optimisation problem. So, in this article, the target is to achieve a model to approximate the performance of a predetermined classifier over each arbitrary dataset. According to this model, an optimisation problem is designed and a genetic algorithm is employed as an optimiser to explore the best classifier set in each subspace. The proposed ensemble methodology is called classifier ensemble based on subspace learning (CEBSL). CEBSL is examined on some datasets and it shows considerable improvements.