Explainable artificial intelligence (XAI) has become increasingly important in biomedical image analysis to promote transparency, trust, and clinical adoption of DL models. While several surveys have reviewed XAI techniques, they often lack a modality-aware perspective, overlook recent advances in multimodal and vision-language paradigms, and provide limited practical guidance. This survey addresses this gap through a comprehensive and structured synthesis of XAI methods tailored to biomedical image analysis.We systematically categorize XAI methods, analyzing their underlying principles, strengths, and limitations within biomedical contexts. A modality-centered taxonomy is proposed to align XAI methods with specific imaging types, highlighting the distinct interpretability challenges across modalities. We further examine the emerging role of multimodal learning and vision-language models in explainable biomedical AI, a topic largely underexplored in previous work. Our contributions also include a summary of widely used evaluation metrics and open-source frameworks, along with a critical discussion of persistent challenges and future directions. This survey offers a timely and in-depth foundation for advancing interpretable DL in biomedical image analysis.
Large Language Models (LLMs) have played a pivotal role in advancing Artificial Intelligence (AI). However, despite their achievements, LLMs often struggle to explain their decision-making processes, making them a 'black box' and presenting a substantial challenge to explainability. This lack of transparency poses a significant obstacle to the adoption of LLMs in high-stakes domain applications, where interpretability is particularly essential. To overcome these limitations, researchers have developed various explainable artificial intelligence (XAI) methods that provide human-interpretable explanations for LLMs. However, a systematic understanding of these methods remains limited. To address this gap, this survey provides a comprehensive review of explainability techniques by categorizing XAI methods based on the underlying transformer architectures of LLMs: encoder-only, decoder-only, and encoder-decoder models. Then these techniques are examined in terms of their evaluation for assessing explainability, and the survey further explores how these explanations are leveraged in practical applications. Finally, it discusses available resources, ongoing research challenges, and future directions, aiming to guide continued efforts toward developing transparent and responsible LLMs.
Integrated Information Theory (IIT) provides a quantitative framework for explaining consciousness phenomenon, positing that conscious systems comprise elements integrated through causal properties. We apply IIT 3.0 and 4.0 -- the latest iterations of this framework -- to sequences of Large Language Model (LLM) representations, analyzing data derived from existing Theory of Mind (ToM) test results. Our study systematically investigates whether the differences of ToM test performances, when presented in the LLM representations, can be revealed by IIT estimates, i.e., $\Phi^{\max}$ (IIT 3.0), $\Phi$ (IIT 4.0), Conceptual Information (IIT 3.0), and $\Phi$-structure (IIT 4.0). Furthermore, we compare these metrics with the Span Representations independent of any estimate for consciousness. This additional effort aims to differentiate between potential "consciousness" phenomena and inherent separations within LLM representational space. We conduct comprehensive experiments examining variations across LLM transformer layers and linguistic spans from stimuli. Our results suggest that sequences of contemporary Transformer-based LLM representations lack statistically significant indicators of observed "consciousness" phenomena but exhibit intriguing patterns under $\textit{spatio}$-permutational analyses. The Appendix and code are available as Supplementary Materials at: https://doi.org/10.1016/j.nlp.2025.100163.
Transformer-based language models excel in a variety of protein-science tasks that range from structure prediction to the design of functional enzymes. However, these models operate as black boxes, and their underlying working principles remain unclear. Here, we survey emerging applications of explainable artificial intelligence (XAI) to protein language models (pLMs) and describe their potential in protein research. We break down the workflow of a generative decoder-only Transformer into four information contexts: (i) training sequences, (ii) input prompt, (iii) model architecture, and (iv) output sequence. For each, we describe existing methods and applications of XAI. Additionally, from published studies we distil five (potential) roles that XAI can play in protein design: Evaluator, Multitasker, Engineer, Coach, and Teacher, with the Evaluator role being the only one widely adopted so far. These roles aim to help both protein science practitioners and model developers understand the possibilities and limitations of implementing XAI for the design of sequences. Finally, we highlight the critical areas of application for the future, including risks related to security, trustworthiness, and bias, and we call for community benchmarks, open-source tooling, and domain-specific visualizations to advance explainable protein design. Overall, our analysis aims to move the discussion toward the use of XAI in protein design.
This article introduces WebXAII, an open-source web framework designed to facilitate research on human interaction with eXplainable Artificial Intelligence (XAI) systems. The field of XAI is rapidly expanding, driven by the growing societal implications of the widespread adoption of AI (and in particular machine learning) across diverse applications. Researchers who study the interaction between humans and XAI techniques typically develop ad hoc interfaces in order to conduct their studies. These interfaces are usually not shared alongside the results of the studies, which limits their reusability and the reproducibility of experiments. In response, we design and implement WebXAII, a web-based platform that can embody full experimental protocols, meaning that it can present all aspects of the experiment to human participants and record their responses. The experimental protocols are translated into a composite architecture of generic views and modules, which offers a lot of flexibility. The architecture is defined in a structured configuration file, so that protocols can be implemented with minimal programming skills. We demonstrate that WebXAII can effectively embody relevant protocols, by reproducing the protocol of a state-of-the-art study of the literature.
Recent developments in the Internet of Bio-Nano Things (IoBNT) are laying the groundwork for innovative applications across the healthcare sector. Nanodevices designed to operate within the body, managed remotely via the internet, are envisioned to promptly detect and actuate on potential diseases. In this vision, an inherent challenge arises due to the limited capabilities of individual nanosensors; specifically, nanosensors must communicate with one another to collaborate as a cluster. Aiming to research the boundaries of the clustering capabilities, this survey emphasizes data-driven communication strategies in molecular communication (MC) channels as a means of linking nanosensors. Relying on the flexibility and robustness of machine learning (ML) methods to tackle the dynamic nature of MC channels, the MC research community frequently refers to neural network (NN) architectures. This interdisciplinary research field encompasses various aspects, including the use of NNs to facilitate communication in MC environments, their implementation at the nanoscale, explainable approaches for NNs, and dataset generation for training. Within this survey, we provide a comprehensive analysis of fundamental perspectives on recent trends in NN architectures for MC, the feasibility of their implementation at the nanoscale, applied explainable artificial intelligence (XAI) techniques, and the accessibility of datasets along with best practices for their generation. Additionally, we offer open-source code repositories that illustrate NN-based methods to support reproducible research for key MC scenarios. Finally, we identify emerging research challenges, such as robust NN architectures, biologically integrated NN modules, and scalable training strategies.
An Advanced Persistent Threat (APT) is a multistage, highly sophisticated, and covert form of cyber threat that gains unauthorized access to networks to either steal valuable data or disrupt the targeted network. These threats often remain undetected for extended periods, emphasizing the critical need for early detection in networks to mitigate potential APT consequences. In this work, we propose a feature selection method for developing a lightweight intrusion detection system capable of effectively identifying APTs at the initial compromise stage. Our approach leverages the XGBoost algorithm and Explainable Artificial Intelligence (XAI), specifically utilizing the SHAP (SHapley Additive exPlanations) method for identifying the most relevant features of the initial compromise stage. The results of our proposed method showed the ability to reduce the selected features of the SCVIC-APT-2021 dataset from 77 to just four while maintaining consistent evaluation metrics for the suggested system. The estimated metrics values are 97% precision, 100% recall, and a 98% F1 score. The proposed method not only aids in preventing successful APT consequences but also enhances understanding of APT behavior at early stages.
Financial literacy is increasingly dependent on the ability to interpret complex financial data and utilize advanced forecasting tools. In this context, this study proposes a novel approach that combines transformer-based time series models with explainable artificial intelligence (XAI) to enhance the interpretability and accuracy of stock price predictions. The analysis focuses on the daily stock prices of the five highest-volume banks listed in the BIST100 index, along with XBANK and XU100 indices, covering the period from January 2015 to March 2025. Models including DLinear, LTSNet, Vanilla Transformer, and Time Series Transformer are employed, with input features enriched by technical indicators. SHAP and LIME techniques are used to provide transparency into the influence of individual features on model outputs. The results demonstrate the strong predictive capabilities of transformer models and highlight the potential of interpretable machine learning to empower individuals in making informed investment decisions and actively engaging in financial markets.
Deep neural networks, particularly Transformers, have been widely adopted for predicting the functional properties of proteins. In this work, we focus on exploring whether Protein Transformers can capture biological intelligence among protein sequences. To achieve our goal, we first introduce a protein function dataset, namely Protein-FN, providing over 9000 protein data with meaningful labels. Second, we devise a new Transformer architecture, namely Sequence Protein Transformers (SPT), for computationally efficient protein function predictions. Third, we develop a novel Explainable Artificial Intelligence (XAI) technique called Sequence Score, which can efficiently interpret the decision-making processes of protein models, thereby overcoming the difficulty of deciphering biological intelligence bided in Protein Transformers. Remarkably, even our smallest SPT-Tiny model, which contains only 5.4M parameters, demonstrates impressive predictive accuracy, achieving 94.3% on the Antibiotic Resistance (AR) dataset and 99.6% on the Protein-FN dataset, all accomplished by training from scratch. Besides, our Sequence Score technique helps reveal that our SPT models can discover several meaningful patterns underlying the sequence structures of protein data, with these patterns aligning closely with the domain knowledge in the biology community. We have officially released our Protein-FN dataset on Hugging Face Datasets https://huggingface.co/datasets/Protein-FN/Protein-FN. Our code is available at https://github.com/fudong03/BioIntelligence.
Brain tumors, regardless of being benign or malignant, pose considerable health risks, with malignant tumors being more perilous due to their swift and uncontrolled proliferation, resulting in malignancy. Timely identification is crucial for enhancing patient outcomes, particularly in nations such as Bangladesh, where healthcare infrastructure is constrained. Manual MRI analysis is arduous and susceptible to inaccuracies, rendering it inefficient for prompt diagnosis. This research sought to tackle these problems by creating an automated brain tumor classification system utilizing MRI data obtained from many hospitals in Bangladesh. Advanced deep learning models, including VGG16, VGG19, and ResNet50, were utilized to classify glioma, meningioma, and various brain cancers. Explainable AI (XAI) methodologies, such as Grad-CAM and Grad-CAM++, were employed to improve model interpretability by emphasizing the critical areas in MRI scans that influenced the categorization. VGG16 achieved the most accuracy, attaining 99.17%. The integration of XAI enhanced the system's transparency and stability, rendering it more appropriate for clinical application in resource-limited environments such as Bangladesh. This study highlights the capability of deep learning models, in conjunction with explainable artificial intelligence (XAI), to enhance brain tumor detection and identification in areas with restricted access to advanced medical technologies.
Over the past decade, Medical Image Segmentation (MIS) using Deep Neural Networks (DNNs) has achieved significant performance improvements and holds great promise for future developments. This paper presents a comprehensive study on MIS based on DNNs. Intelligent Vision Systems are often evaluated based on their output levels, such as Data, Information, Knowledge, Intelligence, and Wisdom (DIKIW),and the state-of-the-art solutions in MIS at these levels are the focus of research. Additionally, Explainable Artificial Intelligence (XAI) has become an important research direction, as it aims to uncover the "black box" nature of previous DNN architectures to meet the requirements of transparency and ethics. The study emphasizes the importance of MIS in disease diagnosis and early detection, particularly for increasing the survival rate of cancer patients through timely diagnosis. XAI and early prediction are considered two important steps in the journey from "intelligence" to "wisdom." Additionally, the paper addresses existing challenges and proposes potential solutions to enhance the efficiency of implementing DNN-based MIS.
Water reuse is a key point when fresh water is a commodity in ever greater demand, but which is also becoming ever more available. Furthermore, the return of clean water to its natural environment is also mandatory. Therefore, wastewater treatment plants (WWTPs) are essential in any policy focused on these serious challenges. WWTPs are complex facilities which need to operate at their best to achieve their goals. Nowadays, they are largely monitored, generating large databases of historical data concerning their functioning over time. All this implies a large amount of embedded information which is not usually easy for plant managers to assimilate, correlate and understand; in other words, for them to know the global operation of the plant at any given time. At this point, the intelligent and Machine Learning (ML) approaches can give support for that need, managing all the data and translating them into manageable, interpretable and explainable knowledge about how the WWTP plant is operating at a glance. Here, an eXplainable Artificial Intelligence (XAI) based methodology is proposed and tested for a real WWTP, in order to extract explainable service knowledge concerning the operation modes of the WWTP managed by AQUAVALL, which is the public service in charge of the integral water cycle in the City Council of Valladolid (Castilla y Le\'on, Spain). By applying well-known approaches of XAI and ML focused on the challenge of WWTP, it has been possible to summarize a large number of historical databases through a few explained operation modes of the plant in a low-dimensional data space, showing the variables and facility units involved in each case.
The use of appropriate methods of Interpretable Machine Learning (IML) and eXplainable Artificial Intelligence (XAI) is essential for adopting black-box predictive models in fields where model and prediction explainability is required. As a novel tool for interpreting black-box models, we introduce the R package midr, which implements Maximum Interpretation Decomposition (MID). MID is a functional decomposition approach that derives a low-order additive representation of a black-box model by minimizing the squared error between the model's prediction function and this additive representation. midr enables learning from black-box models by constructing a global surrogate model with advanced analytical capabilities. After reviewing related work and the theoretical foundation of MID, we demonstrate the package's usage and discuss some of its key features.
Recent explainable artificial intelligence (XAI) methods for time series primarily estimate point-wise attribution magnitudes, while overlooking the directional impact on predictions, leading to suboptimal identification of significant points. Our analysis shows that conventional Integrated Gradients (IG) effectively capture critical points with both positive and negative impacts on predictions. However, current evaluation metrics fail to assess this capability, as they inadvertently cancel out opposing feature contributions. To address this limitation, we propose novel evaluation metrics-Cumulative Prediction Difference (CPD) and Cumulative Prediction Preservation (CPP)-to systematically assess whether attribution methods accurately identify significant positive and negative points in time series XAI. Under these metrics, conventional IG outperforms recent counterparts. However, directly applying IG to time series data may lead to suboptimal outcomes, as generated paths ignore temporal relationships and introduce out-of-distribution samples. To overcome these challenges, we introduce TIMING, which enhances IG by incorporating temporal awareness while maintaining its theoretical properties. Extensive experiments on synthetic and real-world time series benchmarks demonstrate that TIMING outperforms existing time series XAI baselines. Our code is available at https://github.com/drumpt/TIMING.
Counterfactual explanations play a pivotal role in explainable artificial intelligence (XAI) by offering intuitive, human-understandable alternatives that elucidate machine learning model decisions. Despite their significance, existing methods for generating counterfactuals often require constant access to the predictive model, involve computationally intensive optimization for each instance and lack the flexibility to adapt to new user-defined constraints without retraining. In this paper, we propose DiCoFlex, a novel model-agnostic, conditional generative framework that produces multiple diverse counterfactuals in a single forward pass. Leveraging conditional normalizing flows trained solely on labeled data, DiCoFlex addresses key limitations by enabling real-time user-driven customization of constraints such as sparsity and actionability at inference time. Extensive experiments on standard benchmark datasets show that DiCoFlex outperforms existing methods in terms of validity, diversity, proximity, and constraint adherence, making it a practical and scalable solution for counterfactual generation in sensitive decision-making domains.
Artificial Intelligence (AI) is one of the major technological advancements of this century, bearing incredible potential for users through AI-powered applications and tools in numerous domains. Being often black-box (i.e., its decision-making process is unintelligible), developers typically resort to eXplainable Artificial Intelligence (XAI) techniques to interpret the behaviour of AI models to produce systems that are transparent, fair, reliable, and trustworthy. However, presenting explanations to the user is not trivial and is often left as a secondary aspect of the system's design process, leading to AI systems that are not useful to end-users. This paper presents a Systematic Literature Review on Explanation User Interfaces (XUIs) to gain a deeper understanding of the solutions and design guidelines employed in the academic literature to effectively present explanations to users. To improve the contribution and real-world impact of this survey, we also present a framework for Human-cEnteRed developMent of Explainable user interfaceS (HERMES) to guide practitioners and academics in the design and evaluation of XUIs.
Psychiatric disorders affect millions globally, yet their diagnosis faces significant challenges in clinical practice due to subjective assessments and accessibility concerns, leading to potential delays in treatment. To help address this issue, we present Heart2Mind, a human-centered contestable psychiatric disorder diagnosis system using wearable electrocardiogram (ECG) monitors. Our approach leverages cardiac biomarkers, particularly heart rate variability (HRV) and R-R intervals (RRI) time series, as objective indicators of autonomic dysfunction in psychiatric conditions. The system comprises three key components: (1) a Cardiac Monitoring Interface (CMI) for real-time data acquisition from Polar H9/H10 devices; (2) a Multi-Scale Temporal-Frequency Transformer (MSTFT) that processes RRI time series through integrated time-frequency domain analysis; (3) a Contestable Diagnosis Interface (CDI) combining Self-Adversarial Explanations (SAEs) with contestable Large Language Models (LLMs). Our MSTFT achieves 91.7% accuracy on the HRV-ACC dataset using leave-one-out cross-validation, outperforming state-of-the-art methods. SAEs successfully detect inconsistencies in model predictions by comparing attention-based and gradient-based explanations, while LLMs enable clinicians to validate correct predictions and contest erroneous ones. This work demonstrates the feasibility of combining wearable technology with Explainable Artificial Intelligence (XAI) and contestable LLMs to create a transparent, contestable system for psychiatric diagnosis that maintains clinical oversight while leveraging advanced AI capabilities. Our implementation is publicly available at: https://github.com/Analytics-Everywhere-Lab/heart2mind.
Traditional saliency map methods, popularized in computer vision, highlight individual points (pixels) of the input that contribute the most to the model's output. However, in time-series they offer limited insights as semantically meaningful features are often found in other domains. We introduce Cross-domain Integrated Gradients, a generalization of Integrated Gradients. Our method enables feature attributions on any domain that can be formulated as an invertible, differentiable transformation of the time domain. Crucially, our derivation extends the original Integrated Gradients into the complex domain, enabling frequency-based attributions. We provide the necessary theoretical guarantees, namely, path independence and completeness. Our approach reveals interpretable, problem-specific attributions that time-domain methods cannot capture, on three real-world tasks: wearable sensor heart rate extraction, electroencephalography-based seizure detection, and zero-shot time-series forecasting. We release an open-source Tensorflow/PyTorch library to enable plug-and-play cross-domain explainability for time-series models. These results demonstrate the ability of cross-domain integrated gradients to provide semantically meaningful insights in time-series models that are impossible with traditional time-domain saliency.
While Graph Neural Networks (GNNs) have become the de facto model for learning from structured data, their decisional process remains opaque to the end user, undermining their deployment in safety-critical applications. In the case of graph classification, Explainable Artificial Intelligence (XAI) techniques address this major issue by identifying sub-graph motifs that explain predictions. However, advancements in this field are hindered by a chronic scarcity of benchmark datasets with known ground-truth motifs to assess the explanations' quality. Current graph XAI benchmarks are limited to synthetic data or a handful of real-world tasks hand-curated by domain experts. In this paper, we propose a general method to automate the construction of XAI benchmarks for graph classification from real-world datasets. We provide both 15 ready-made benchmarks, as well as the code to generate more than 2000 additional XAI benchmarks with our method. As a use case, we employ our benchmarks to assess the effectiveness of some popular graph explainers.
Counterfactuals play a pivotal role in the two distinct data science fields of causal inference (CI) and explainable artificial intelligence (XAI). While the core idea behind counterfactuals remains the same in both fields--the examination of what would have happened under different circumstances--there are key differences in how they are used and interpreted. We introduce a formal definition that encompasses the multi-faceted concept of the counterfactual in CI and XAI. We then discuss how counterfactuals are used, evaluated, generated, and operationalized in CI vs. XAI, highlighting conceptual and practical differences. By comparing and contrasting the two, we hope to identify opportunities for cross-fertilization across CI and XAI.