Interleukin-6 (IL-6) is a key immunomodulatory cytokine implicated in diverse physiological processes and pathological conditions, including autoimmune diseases, cancers, and cytokine storms. Immunogenic peptides capable of inducing IL-6 expression are key modulators of host immune responses and represent promising candidates for therapeutic design and epitope-based vaccine development. However, experimental identification of IL-6-inducing peptides remains laborious and unsuitable for large-scale screening. Although existing computational approaches show promise, many often struggle to capture both global contextual semantics and local motif-level features essential for peptide immunogenicity. To address these limitations, we present CONTRA-IL6, a novel deep learning framework that integrates Transformer fusion and convolutional localization modules with stacked pretrained protein language model embeddings to predict IL-6-inducing peptides. Comprehensive benchmarking on an independent dataset demonstrates that CONTRA-IL6 achieves superior predictive performance over six state-of-the-art predictors. Notably, it achieves the highest Matthews correlation coefficient (MCC, 0.504) and F1 (0.549) and improves over the best-performing existing method by 3.2% in MCC and 4.3% in F1, demonstrating balanced and robust performance. Feature space visualizations (uniform manifold approximation and projection, kernel density estimation) showed clear class separation, while 1D gradient-weighted class activation mapping++ highlighted strong attention to specific C-terminal regions. Crucially, we moved beyond these attribution methods by employing in silico mutagenesis, which causally confirmed the functional importance and physicochemical constraints. Ablation studies further confirmed the synergistic contribution of global and local modules to model performance. CONTRA-IL6 offers a robust, scalable, and interpretable solution for immunoinformatics research. The standalone package is freely available at https://pypi.org/project/contra-il6/ to facilitate broader community use.

The increasing demand for autonomous systems in complex and dynamic environments has driven significant research into intelligent path planning methodologies. For decades, graph-based search algorithms, linear programming techniques, and evolutionary computation methods have served as foundational approaches in this domain. Recently, deep reinforcement learning (DRL) has emerged as a powerful method for enabling autonomous agents to learn optimal navigation strategies through interaction with their environments. This survey provides a comprehensive overview of traditional approaches as well as the recent advancements in DRL applied to path planning tasks, focusing on autonomous vehicles, drones, and robotic platforms. Key algorithms across both conventional and learning-based paradigms are categorized, with their innovations and practical implementations highlighted. This is followed by a thorough discussion of their respective strengths and limitations in terms of computational efficiency, scalability, adaptability, and robustness. The survey concludes by identifying key open challenges and outlining promising avenues for future research. Special attention is given to hybrid approaches that integrate DRL with classical planning techniques to leverage the benefits of both learning-based adaptability and deterministic reliability, offering promising directions for robust and resilient autonomous navigation.

Large language models (LLMs) have significantly advanced computational biology by enabling the integration of molecular, protein, and natural language data to accelerate drug discovery. However, existing molecular captioning approaches often underutilize diverse molecular modalities and lack interpretability. In this study, we introduce XMolCap, a novel explainable molecular captioning framework that integrates molecular images, SMILES strings, and graph-based structures through a stacked multimodal fusion mechanism. The framework is built upon a BioT5-based encoder-decoder architecture, which serves as the backbone for extracting feature representations from SELFIES. By leveraging specialized models such as SwinOCSR, SciBERT, and GIN-MoMu, XMolCap effectively captures complementary information from each modality. Our model not only achieves state-of-the-art performance on two benchmark datasets (L+M-24 and ChEBI-20), outperforming several strong baselines, but also provides detailed, functional group-aware, and property-specific explanations through graph-based interpretation. XMolCap is publicly available at https://github.com/cbbl-skku-org/XMolCap/ for reproducibility and local deployment. We believe it holds strong potential for clinical and pharmaceutical applications by generating accurate, interpretable molecular descriptions that deepen our understanding of molecular properties and interactions.

The worldwide appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated significant concern and posed a considerable challenge to global health. Phosphorylation is a common post-translational modification that affects many vital cellular functions and is closely associated with SARS-CoV-2 infection. Precise identification of phosphorylation sites could provide more in-depth insight into the processes underlying SARS-CoV-2 infection and help alleviate the continuing COVID-19 crisis. Currently, available computational tools for predicting these sites lack accuracy and effectiveness. In this study, we designed an innovative meta-learning model, Meta-Learning for Serine/Threonine Phosphorylation (MeL-STPhos), to precisely identify protein phosphorylation sites. We initially performed a comprehensive assessment of 29 unique sequence-derived features, establishing prediction models for each using 14 renowned machine learning methods, ranging from traditional classifiers to advanced deep learning algorithms. We then selected the most effective model for each feature by integrating the predicted values. Rigorous feature selection strategies were employed to identify the optimal base models and classifier(s) for each cell-specific dataset. To the best of our knowledge, this is the first study to report two cell-specific models and a generic model for phosphorylation site prediction by utilizing an extensive range of sequence-derived features and machine learning algorithms. Extensive cross-validation and independent testing revealed that MeL-STPhos surpasses existing state-of-the-art tools for phosphorylation site prediction. We also developed a publicly accessible platform at https://balalab-skku.org/MeL-STPhos. We believe that MeL-STPhos will serve as a valuable tool for accelerating the discovery of serine/threonine phosphorylation sites and elucidating their role in post-translational regulation.

2'-O-methylation (2OM) is the most common post-transcriptional modification of RNA. It plays a crucial role in RNA splicing, RNA stability and innate immunity. Despite advances in high-throughput detection, the chemical stability of 2OM makes it difficult to detect and map in messenger RNA. Therefore, bioinformatics tools have been developed using machine learning (ML) algorithms to identify 2OM sites. These tools have made significant progress, but their performances remain unsatisfactory and need further improvement. In this study, we introduced H2Opred, a novel hybrid deep learning (HDL) model for accurately identifying 2OM sites in human RNA. Notably, this is the first application of HDL in developing four nucleotide-specific models [adenine (A2OM), cytosine (C2OM), guanine (G2OM) and uracil (U2OM)] as well as a generic model (N2OM). H2Opred incorporated both stacked 1D convolutional neural network (1D-CNN) blocks and stacked attention-based bidirectional gated recurrent unit (Bi-GRU-Att) blocks. 1D-CNN blocks learned effective feature representations from 14 conventional descriptors, while Bi-GRU-Att blocks learned feature representations from five natural language processing-based embeddings extracted from RNA sequences. H2Opred integrated these feature representations to make the final prediction. Rigorous cross-validation analysis demonstrated that H2Opred consistently outperforms conventional ML-based single-feature models on five different datasets. Moreover, the generic model of H2Opred demonstrated a remarkable performance on both training and testing datasets, significantly outperforming the existing predictor and other four nucleotide-specific H2Opred models. To enhance accessibility and usability, we have deployed a user-friendly web server for H2Opred, accessible at https://balalab-skku.org/H2Opred/. This platform will serve as an invaluable tool for accurately predicting 2OM sites within human RNA, thereby facilitating broader applications in relevant research endeavors.

Abstract Reinforcement learning (RL) has emerged as an effective approach for building an intelligent system, which involves multiple self-operated agents to collectively accomplish a designated task. More importantly, there has been a renewed focus on RL since the introduction of deep learning that essentially makes RL feasible to operate in high-dimensional environments. However, there are many diversified research directions in the current literature, such as multi-agent and multi-objective learning, and human-machine interactions. Therefore, in this paper, we propose a comprehensive software architecture that not only plays a vital role in designing a connect-the-dots deep RL architecture but also provides a guideline to develop a realistic RL application in a short time span. By inheriting the proposed architecture, software managers can foresee any challenges when designing a deep RL-based system. As a result, they can expedite the design process and actively control every stage of software development, which is especially critical in agile development environments. For this reason, we design a deep RL-based framework that strictly ensures flexibility, robustness, and scalability. To enforce generalization, the proposed architecture also does not depend on a specific RL algorithm, a network configuration, the number of agents, or the type of agents.

Recently, speech emotion recognition (SER) has become an active research area in speech processing, particularly with the advent of deep learning (DL). Numerous DL-based methods have been proposed for SER. However, most of the existing DL-based models are complex and require a large amounts of data to achieve a good performance. In this study, a new framework of deep attention-based dilated convolutional-recurrent neural networks coupled with a hybrid data augmentation method was proposed for addressing SER tasks. The hybrid data augmentation method constitutes an upsampling technique for generating more speech data samples based on the traditional and generative adversarial network approaches. By leveraging both convolutional and recurrent neural networks in a dilated form along with an attention mechanism, the proposed DL framework can extract high-level representations from three-dimensional log Mel spectrogram features. Dilated convolutional neural networks acquire larger receptive fields, whereas dilated recurrent neural networks overcome complex dependencies as well as the vanishing and exploding gradient issues. Furthermore, the loss functions are reconfigured by combining the SoftMax loss and the center-based losses to classify various emotional states. The proposed framework was implemented using the Python programming language and the TensorFlow deep learning library. To validate the proposed framework, the EmoDB and ERC benchmark datasets, which are imbalanced and/or small datasets, were employed. The experimental results indicate that the proposed framework outperforms other related state-of-the-art methods, yielding the highest unweighted recall rates of 88.03 ± 1.39 (%) and 66.56 ± 0.67 (%) for the EmoDB and ERC datasets, respectively.

The optimal number of clusters (Copt) is one of the determinants of clustering efficiency. In this article, we present a new method of quantifyingCoptfor centroid-based clustering. First, we propose a new clustering validity index named fRisk(C) based on the fuzzy set theory. It takes the role of normalization and accumulation of local risks coming from each action either splitting data from a cluster or merging data into a cluster. fRisk(C) exploits the local distribution information of the database to catch the global information of the clustering process in the form of the risk degree. Based on the monotonous reduction property of fRisk(C), which is proved theoretically, we present a fRisk-based new algorithm named fRisk4-bA for determiningCopt. In the algorithm, the well-known L-method is employed as a supplemented tool to catchCopton the graph of the fRisk(C). Along with the stable convergence trend of the method to be proved theoretically, numerical surveys are also carried out. The surveys show that the high reliability and stability, as well as the sensitivity in separating/merging clusters in high-density areas, even if the presence of noise in the databases, are the strong points of the proposed method.