Next activity prediction represents a fundamental challenge for optimizing business processes in service-oriented architectures such as microservices environments, distributed enterprise systems, and cloud-native platforms, which enables proactive resource allocation and dynamic service composition. Despite the prevalence of sequence-based methods, these approaches fail to capture non-sequential relationships that arise from parallel executions and conditional dependencies. Even though graph-based approaches address structural preservation, they suffer from homogeneous representations and static structures that apply uniform modeling strategies regardless of individual process complexity characteristics. To address these limitations, we introduce RLHGNN, a novel framework that transforms event logs into heterogeneous process graphs with three distinct edge types grounded in established process mining theory. Our approach creates four flexible graph structures by selectively combining these edges to accommodate different process complexities, and employs reinforcement learning formulated as a Markov Decision Process to automatically determine the optimal graph structure for each specific process instance. RLHGNN then applies heterogeneous graph convolution with relation-specific aggregation strategies to effectively predict the next activity. This adaptive methodology enables precise modeling of both sequential and non-sequential relationships in service interactions. Comprehensive evaluation on six real-world datasets demonstrates that RLHGNN consistently outperforms state-of-the-art approaches. Furthermore, it maintains an inference latency of approximately 1 ms per prediction, representing a highly practical solution suitable for real-time business process monitoring applications. The source code is available at https://github.com/Joker3993/RLHGNN.
Peptide-drug conjugates (PDCs) represent a promising therapeutic avenue for human diseases, particularly in cancer treatment. Systematic elucidation of structure-activity relationships (SARs) and accurate prediction of the activity of PDCs are critical for the rational design and optimization of these conjugates. To this end, we carefully design and construct a benchmark PDCs dataset compiled from literature-derived collections and PDCdb database, and then develop PDCNet, the first unified deep learning framework for forecasting the activity of PDCs. The architecture systematically captures the complex factors underlying anticancer decisions of PDCs in real-word scenarios through a multi-level feature fusion framework that collaboratively characterizes and learns the features of peptides, linkers, and payloads. Leveraging a curated PDCs benchmark dataset, comprehensive evaluation results show that PDCNet demonstrates superior predictive capability, with the highest AUC, F1, MCC and BA scores of 0.9213, 0.7656, 0.7071 and 0.8388 for the test set, outperforming eight established traditional machine learning models. Multi-level validations, including 5-fold cross-validation, threshold testing, ablation studies, model interpretability analysis and external independent testing, further confirm the superiority, robustness, and usability of the PDCNet architecture. We anticipate that PDCNet represents a novel paradigm, incorporating both a benchmark dataset and advanced models, which can accelerate the design and discovery of new PDC-based therapeutic agents.
Predicting guide RNA (gRNA) activity is critical for effective CRISPR-Cas12 genome editing but remains challenging due to limited data, variation across protospacer adjacent motifs (PAMs-short sequence requirements for Cas binding), and reliance on large-scale training. We investigate whether pre-trained biological foundation model originally trained on transcriptomic data can improve gRNA activity estimation even without domain-specific pre-training. Using embeddings from existing RNA foundation model as input to lightweight regressor, we show substantial gains over traditional baselines. We also integrate chromatin accessibility data to capture regulatory context, improving performance further. Our results highlight the effectiveness of pre-trained foundation models and chromatin accessibility data for gRNA activity prediction.
Artificial Intelligence (AI) is accelerating the transformation of scientific research paradigms, not only enhancing research efficiency but also driving innovation. We introduce NovelSeek, a unified closed-loop multi-agent framework to conduct Autonomous Scientific Research (ASR) across various scientific research fields, enabling researchers to tackle complicated problems in these fields with unprecedented speed and precision. NovelSeek highlights three key advantages: 1) Scalability: NovelSeek has demonstrated its versatility across 12 scientific research tasks, capable of generating innovative ideas to enhance the performance of baseline code. 2) Interactivity: NovelSeek provides an interface for human expert feedback and multi-agent interaction in automated end-to-end processes, allowing for the seamless integration of domain expert knowledge. 3) Efficiency: NovelSeek has achieved promising performance gains in several scientific fields with significantly less time cost compared to human efforts. For instance, in reaction yield prediction, it increased from 27.6% to 35.4% in just 12 hours; in enhancer activity prediction, accuracy rose from 0.52 to 0.79 with only 4 hours of processing; and in 2D semantic segmentation, precision advanced from 78.8% to 81.0% in a mere 30 hours.
We present the Boltzmann classifier, a novel distance based probabilistic classification algorithm inspired by the Boltzmann distribution. Unlike traditional classifiers that produce hard decisions or uncalibrated probabilities, the Boltzmann classifier assigns class probabilities based on the average distance to the nearest neighbors within each class, providing interpretable, physically meaningful outputs. We evaluate the performance of the method across three application domains: molecular activity prediction, oxidation state classification of transition metal complexes, and breast cancer diagnosis. In the molecular activity task, the classifier achieved the highest accuracy in predicting active compounds against two protein targets, with strong correlations observed between the predicted probabilities and experimental pIC50 values. For metal complexes, the classifier accurately distinguished between oxidation states II and III for Fe, Mn, and Co, using only metal-ligand bond lengths extracted from crystallographic data, and demonstrated high consistency with known chemical trends. In the breast cancer dataset, the classifier achieved 97% accuracy, with low confidence predictions concentrated in inherently ambiguous cases. Across all tasks, the Boltzmann classifier performed competitively or better than standard models such as logistic regression, support vector machines, random forests, and k-nearest neighbors. Its probabilistic outputs were found to correlate with continuous physical or biological properties, highlighting its potential utility in both classification and regression contexts. The results suggest that the Boltzmann classifier is a robust and interpretable alternative to conventional machine learning approaches, particularly in scientific domains where underlying structure property relationships are important.
With robots increasingly integrating into human environments, understanding and predicting human motion is essential for safe and efficient interactions. Modern human motion and activity prediction approaches require high quality and quantity of data for training and evaluation, usually collected from motion capture systems, onboard or stationary sensors. Setting up these systems is challenging due to the intricate setup of hardware components, extensive calibration procedures, occlusions, and substantial costs. These constraints make deploying such systems in new and large environments difficult and limit their usability for in-the-wild measurements. In this paper we investigate the possibility to apply the novel Ultra-Wideband (UWB) localization technology as a scalable alternative for human motion capture in crowded and occlusion-prone environments. We include additional sensing modalities such as eye-tracking, onboard robot LiDAR and radar sensors, and record motion capture data as ground truth for evaluation and comparison. The environment imitates a museum setup, with up to four active participants navigating toward random goals in a natural way, and offers more than 130 minutes of multi-modal data. Our investigation provides a step toward scalable and accurate motion data collection beyond vision-based systems, laying a foundation for evaluating sensing modalities like UWB in larger and complex environments like warehouses, airports, or convention centers.
Predicting human behavior in shared environments is crucial for safe and efficient human-robot interaction. Traditional data-driven methods to that end are pre-trained on domain-specific datasets, activity types, and prediction horizons. In contrast, the recent breakthroughs in Large Language Models (LLMs) promise open-ended cross-domain generalization to describe various human activities and make predictions in any context. In particular, Multimodal LLMs (MLLMs) are able to integrate information from various sources, achieving more contextual awareness and improved scene understanding. The difficulty in applying general-purpose MLLMs directly for prediction stems from their limited capacity for processing large input sequences, sensitivity to prompt design, and expensive fine-tuning. In this paper, we present a systematic analysis of applying pre-trained MLLMs for context-aware human behavior prediction. To this end, we introduce a modular multimodal human activity prediction framework that allows us to benchmark various MLLMs, input variations, In-Context Learning (ICL), and autoregressive techniques. Our evaluation indicates that the best-performing framework configuration is able to reach 92.8% semantic similarity and 66.1% exact label accuracy in predicting human behaviors in the target frame.
Tasks in Predictive Business Process Monitoring (PBPM), such as Next Activity Prediction, focus on generating useful business predictions from historical case logs. Recently, Deep Learning methods, particularly sequence-to-sequence models like Long Short-Term Memory (LSTM), have become a dominant approach for tackling these tasks. However, to enhance model transparency, build trust in the predictions, and gain a deeper understanding of business processes, it is crucial to explain the decisions made by these models. Existing explainability methods for PBPM decisions are typically *post-hoc*, meaning they provide explanations only after the model has been trained. Unfortunately, these post-hoc approaches have shown to face various challenges, including lack of faithfulness, high computational costs and a significant sensitivity to out-of-distribution samples. In this work, we introduce, to the best of our knowledge, the first *self-explaining neural network* architecture for predictive process monitoring. Our framework trains an LSTM model that not only provides predictions but also outputs a concise explanation for each prediction, while adapting the optimization objective to improve the reliability of the explanation. We first demonstrate that incorporating explainability into the training process does not hurt model performance, and in some cases, actually improves it. Additionally, we show that our method outperforms post-hoc approaches in terms of both the faithfulness of the generated explanations and substantial improvements in efficiency.
The effectiveness of Spatio-temporal Graph Neural Networks (STGNNs) in time-series applications is often limited by their dependence on fixed, hand-crafted input graph structures. Motivated by insights from the Topological Data Analysis (TDA) paradigm, of which real-world data exhibits multi-scale patterns, we construct several graphs using \textit{Persistent Homology Filtration} -- a mathematical framework describing the multiscale structural properties of data points. Then, we use the constructed graphs as an input to create an ensemble of Graph Neural Networks. The ensemble aggregates the signals from the individual learners via an attention-based routing mechanism, thus systematically encoding the inherent multiscale structures of data. Four different real-world experiments on seismic activity prediction and traffic forecasting (PEMS-BAY, METR-LA) demonstrate that our approach consistently outperforms single-graph baselines while providing interpretable insights.
Data-driven benchmarks have led to significant progress in key scientific modeling domains including weather and structural biology. Here, we introduce the Zebrafish Activity Prediction Benchmark (ZAPBench) to measure progress on the problem of predicting cellular-resolution neural activity throughout an entire vertebrate brain. The benchmark is based on a novel dataset containing 4d light-sheet microscopy recordings of over 70,000 neurons in a larval zebrafish brain, along with motion stabilized and voxel-level cell segmentations of these data that facilitate development of a variety of forecasting methods. Initial results from a selection of time series and volumetric video modeling approaches achieve better performance than naive baseline methods, but also show room for further improvement. The specific brain used in the activity recording is also undergoing synaptic-level anatomical mapping, which will enable future integration of detailed structural information into forecasting methods.
Large-scale neuronal activity recordings with fluorescent calcium indicators are increasingly common, yielding high-resolution 2D or 3D videos. Traditional analysis pipelines reduce this data to 1D traces by segmenting regions of interest, leading to inevitable information loss. Inspired by the success of deep learning on minimally processed data in other domains, we investigate the potential of forecasting neuronal activity directly from volumetric videos. To capture long-range dependencies in high-resolution volumetric whole-brain recordings, we design a model with large receptive fields, which allow it to integrate information from distant regions within the brain. We explore the effects of pre-training and perform extensive model selection, analyzing spatio-temporal trade-offs for generating accurate forecasts. Our model outperforms trace-based forecasting approaches on ZAPBench, a recently proposed benchmark on whole-brain activity prediction in zebrafish, demonstrating the advantages of preserving the spatial structure of neuronal activity.
Accurate prediction of CB2 receptor ligand activity is pivotal for advancing drug discovery targeting this receptor, which is implicated in inflammation, pain management, and neurodegenerative conditions. Although conventional machine learning and deep learning techniques have shown promise, their limited interpretability remains a significant barrier to rational drug design. In this work, we introduce CB2former, a framework that combines a Graph Convolutional Network with a Transformer architecture to predict CB2 receptor ligand activity. By leveraging the Transformer's self attention mechanism alongside the GCN's structural learning capability, CB2former not only enhances predictive performance but also offers insights into the molecular features underlying receptor activity. We benchmark CB2former against diverse baseline models including Random Forest, Support Vector Machine, K Nearest Neighbors, Gradient Boosting, Extreme Gradient Boosting, Multilayer Perceptron, Convolutional Neural Network, and Recurrent Neural Network and demonstrate its superior performance with an R squared of 0.685, an RMSE of 0.675, and an AUC of 0.940. Moreover, attention weight analysis reveals key molecular substructures influencing CB2 receptor activity, underscoring the model's potential as an interpretable AI tool for drug discovery. This ability to pinpoint critical molecular motifs can streamline virtual screening, guide lead optimization, and expedite therapeutic development. Overall, our results showcase the transformative potential of advanced AI approaches exemplified by CB2former in delivering both accurate predictions and actionable molecular insights, thus fostering interdisciplinary collaboration and innovation in drug discovery.
Purpose - In Business Process Management (BPM), accurate prediction of the next activities is vital for operational efficiency and decision-making. Current Artificial Intelligence (AI)/Machine Learning (ML) models struggle with the complexity and evolving nature of business process event logs, balancing accuracy and interpretability. This paper proposes an entropy-driven model selection approach and DAW-Transformer, which stands for Dynamic Attribute-Aware Transformer, to integrate all attributes with a dynamic window for better accuracy. Design/methodology/approach - This paper introduces a novel next-activity prediction approach that uses process entropy to assess the complexity of event logs and dynamically select the most suitable ML model. A new transformer-based architecture with multi-head attention and dynamic windowing mechanism, DAW-Transformer, is proposed to capture long-range dependencies and utilize all relevant event log attributes. Experiments were conducted on six public datasets, and the performance was evaluated with process entropy. Finding - The results demonstrate the effectiveness of the approach across these publicly available datasets. DAW-Transformer achieved superior performance, especially on high-entropy datasets such as Sepsis exceeding Limited window Multi-Transformers by 4.69% and a benchmark CNN-LSTM-SAtt model by 3.07%. For low-entropy datasets like Road Traffic Fine, simpler, more interpretable algorithms like Random Forest performed nearly as well as the more complex DAW-Transformer and offered better handling of imbalanced data and improved explainability. Originality/ value - This work's novelty lies in the proposed DAW-Transformer, with a dynamic window and considering all relevant attributes. Also, entropy-driven selection methods offer a robust, accurate, and interpretable solution for next-activity prediction.
Monoclonal antibodies (mAbs) represent one of the most prevalent FDA-approved modalities for treating autoimmune diseases, infectious diseases, and cancers. However, discovery and development of therapeutic antibodies remains a time-consuming and expensive process. Recent advancements in machine learning (ML) and artificial intelligence (AI) have shown significant promise in revolutionizing antibody discovery and optimization. In particular, models that predict antibody biological activity enable in-silico evaluation of binding and functional properties; such models can prioritize antibodies with the highest likelihoods of success in costly and time-intensive laboratory testing procedures. We here explore an AI model for predicting the binding and receptor blocking activity of antibodies against influenza A hemagglutinin (HA) antigens. Our present model is developed with the MAMMAL framework for biologics discovery to predict antibody-antigen interactions using only sequence information. To evaluate the model's performance, we tested it under various data split conditions to mimic real-world scenarios. Our models achieved an AUROC $\geq$ 0.91 for predicting the activity of existing antibodies against seen HAs and an AUROC of 0.9 for unseen HAs. For novel antibody activity prediction, the AUROC was 0.73, which further declined to 0.63-0.66 under stringent constraints on similarity to existing antibodies. These results demonstrate the potential of AI foundation models to transform antibody design by reducing dependence on extensive laboratory testing and enabling more efficient prioritization of antibody candidates. Moreover, our findings emphasize the critical importance of diverse and comprehensive antibody datasets to improve the generalization of prediction models, particularly for novel antibody development.
Accurate prediction of molecular activities is crucial for efficient drug discovery, yet remains challenging due to limited and noisy datasets. We introduce Similarity-Quantized Relative Learning (SQRL), a learning framework that reformulates molecular activity prediction as relative difference learning between structurally similar pairs of compounds. SQRL uses precomputed molecular similarities to enhance training of graph neural networks and other architectures, and significantly improves accuracy and generalization in low-data regimes common in drug discovery. We demonstrate its broad applicability and real-world potential through benchmarking on public datasets as well as proprietary industry data. Our findings demonstrate that leveraging similarity-aware relative differences provides an effective paradigm for molecular activity prediction.
Biologists frequently desire protein inhibitors for a variety of reasons, including use as research tools for understanding biological processes and application to societal problems in agriculture, healthcare, etc. Immunotherapy, for instance, relies on immune checkpoint inhibitors to block checkpoint proteins, preventing their binding with partner proteins and boosting immune cell function against abnormal cells. Inhibitor discovery has long been a tedious process, which in recent years has been accelerated by computational approaches. Advances in artificial intelligence now provide an opportunity to make inhibitor discovery smarter than ever before. While extensive research has been conducted on computer-aided inhibitor discovery, it has mainly focused on either sequence-to-structure mapping, reverse mapping, or bio-activity prediction, making it unrealistic for biologists to utilize such tools. Instead, our work proposes a new method of computer-assisted inhibitor discovery: de novo pocket-aware peptide structure and sequence generation network. Our approach consists of two sequential diffusion models for end-to-end structure generation and sequence prediction. By leveraging angle and dihedral relationships between backbone atoms, we ensure an E(3)-invariant representation of peptide structures. Our results demonstrate that our method achieves comparable performance to state-of-the-art models, highlighting its potential in pocket-aware peptide design. This work offers a new approach for precise drug discovery using receptor-specific peptide generation.
Peptide therapeutics, including macrocycles, peptide inhibitors, and bioactive linear peptides, play a crucial role in therapeutic development due to their unique physicochemical properties. However, predicting these properties remains challenging. While structure-based models primarily focus on local interactions, language models are capable of capturing global therapeutic properties of both modified and linear peptides. Protein language models like ESM-2, though effective for natural peptides, cannot however encode chemical modifications. Conversely, pre-trained chemical language models excel in representing small molecule properties but are not optimized for peptides. To bridge this gap, we introduce PepDoRA, a unified peptide representation model. Leveraging Weight-Decomposed Low-Rank Adaptation (DoRA), PepDoRA efficiently fine-tunes the ChemBERTa-77M-MLM on a masked language model objective to generate optimized embeddings for downstream property prediction tasks involving both modified and unmodified peptides. By tuning on a diverse and experimentally valid set of 100,000 modified, bioactive, and binding peptides, we show that PepDoRA embeddings capture functional properties of input peptides, enabling the accurate prediction of membrane permeability, non-fouling and hemolysis propensity, and via contrastive learning, target protein-specific binding. Overall, by providing a unified representation for chemically and biologically diverse peptides, PepDoRA serves as a versatile tool for function and activity prediction, facilitating the development of peptide therapeutics across a broad spectrum of applications.
Real-time lower limb movement resistance monitoring is critical for various applications in clinical and sports settings, such as rehabilitation and athletic training. Current methods often face limitations in accuracy, computational efficiency, and generalizability, which hinder their practical implementation. To address these challenges, we propose a novel Mobile Multi-Task Learning Network (MMTL-Net) that integrates MobileNetV3 for efficient feature extraction and employs multi-task learning to simultaneously predict resistance levels and recognize activities. The advantages of MMTL-Net include enhanced accuracy, reduced latency, and improved computational efficiency, making it highly suitable for real-time applications. Experimental results demonstrate that MMTL-Net significantly outperforms existing models on the UCI Human Activity Recognition and Wireless Sensor Data Mining Activity Prediction datasets, achieving a lower Force Error Rate (FER) of 6.8% and a higher Resistance Prediction Accuracy (RPA) of 91.2%. Additionally, the model shows a Real-time Responsiveness (RTR) of 12 milliseconds and a Throughput (TP) of 33 frames per second. These findings underscore the model's robustness and effectiveness in diverse real-world scenarios. The proposed framework not only advances the state-of-the-art in resistance monitoring but also paves the way for more efficient and accurate systems in clinical and sports applications. In real-world settings, the practical implications of MMTL-Net include its potential to enhance patient outcomes in rehabilitation and improve athletic performance through precise, real-time monitoring and feedback.
Current generative models for drug discovery primarily use molecular docking as an oracle to guide the generation of active compounds. However, such models are often not useful in practice because even compounds with high docking scores do not consistently show real-world experimental activity. More accurate methods for activity prediction exist, such as molecular dynamics based binding free energy calculations, but they are too computationally expensive to use in a generative model. To address this challenge, we propose Multi-Fidelity Latent space Active Learning (MF-LAL), a generative modeling framework that integrates a set of oracles with varying cost-accuracy tradeoffs. Using active learning, we train a surrogate model for each oracle and use these surrogates to guide generation of compounds with high predicted activity. Unlike previous approaches that separately learn the surrogate model and generative model, MF-LAL combines the generative and multi-fidelity surrogate models into a single framework, allowing for more accurate activity prediction and higher quality samples. Our experiments on two disease-relevant proteins show that MF-LAL produces compounds with significantly better binding free energy scores than other single and multi-fidelity approaches (~50% improvement in mean binding free energy score). The code is available at https://github.com/Rose-STL-Lab/MF-LAL.
Antibody-drug conjugates (ADCs) have emerged as a promising class of targeted cancer therapeutics, but the design and optimization of their cytotoxic payloads remain challenging. This study introduces DumplingGNN, a novel hybrid Graph Neural Network architecture specifically designed for predicting ADC payload activity based on chemical structure. By integrating Message Passing Neural Networks (MPNN), Graph Attention Networks (GAT), and GraphSAGE layers, DumplingGNN effectively captures multi-scale molecular features and leverages both 2D topological and 3D structural information. We evaluate DumplingGNN on a comprehensive ADC payload dataset focusing on DNA Topoisomerase I inhibitors, as well as on multiple public benchmarks from MoleculeNet. DumplingGNN achieves state-of-the-art performance across several datasets, including BBBP (96.4\% ROC-AUC), ToxCast (78.2\% ROC-AUC), and PCBA (88.87\% ROC-AUC). On our specialized ADC payload dataset, it demonstrates exceptional accuracy (91.48\%), sensitivity (95.08\%), and specificity (97.54\%). Ablation studies confirm the synergistic effects of the hybrid architecture and the critical role of 3D structural information in enhancing predictive accuracy. The model's strong interpretability, enabled by attention mechanisms, provides valuable insights into structure-activity relationships. DumplingGNN represents a significant advancement in molecular property prediction, with particular promise for accelerating the design and optimization of ADC payloads in targeted cancer therapy development.