Research Papers

Geometric deep learning assists protein engineering. Opportunities and Challenges

Julián García-Vinuesa, Jorge Rojas, Nicole Soto-García +7

Protein engineering is experiencing a paradigmatic shift through the integration of geometric deep learning into computational design workflows. While traditional strategies, such as rational design and directed evolution, have enabled relevant advances, they remain limited by the complexity of sequence space and the cost of experimental validation. Geometric deep learning addresses these limitations by operating on non-Euclidean domains, capturing spatial, topological, and physicochemical features essential to protein function. This perspective outlines the current applications of GDL across stability prediction, functional annotation, molecular interaction modeling, and de novo protein design. We highlight recent methodological advances in model generalization, interpretability, and robustness, particularly under data-scarce conditions. A unified framework is proposed that integrates GDL with explainable AI and structure-based validation to support transparent, autonomous design. As GDL converges with generative modeling and high-throughput experimentation, it is emerging as a central technology in next-generation protein engineering and synthetic biology.

We Are AI: Taking Control of Technology

Julia Stoyanovich, Armanda Lewis, Eric Corbett +3

Responsible AI (RAI) is the science and practice of ensuring the design, development, use, and oversight of AI are socially sustainable--benefiting diverse stakeholders while controlling the risks. Achieving this goal requires active engagement and participation from the broader public. This paper introduces "We are AI: Taking Control of Technology," a public education course that brings the topics of AI and RAI to the general audience in a peer-learning setting. We outline the goals behind the course's development, discuss the multi-year iterative process that shaped its creation, and summarize its content. We also discuss two offerings of We are AI to an active and engaged group of librarians and professional staff at New York University, highlighting successes and areas for improvement. The course materials, including a multilingual comic book series by the same name, are publicly available and can be used independently. By sharing our experience in creating and teaching We are AI, we aim to introduce these resources to the community of AI educators, researchers, and practitioners, supporting their public education efforts.

Creating systems that are aligned with our goals is seen as a leading approach to create safe and beneficial AI in both leading AI companies and the academic field of AI safety. We defend the view that misaligned AGI - future, generally intelligent (robotic) AI agents - poses catastrophic risks. At the same time, we support the view that aligned AGI creates a substantial risk of catastrophic misuse by humans. While both risks are severe and stand in tension with one another, we show that - in principle - there is room for alignment approaches which do not increase misuse risk. We then investigate how the tradeoff between misalignment and misuse looks empirically for different technical approaches to AI alignment. Here, we argue that many current alignment techniques and foreseeable improvements thereof plausibly increase risks of catastrophic misuse. Since the impacts of AI depend on the social context, we close by discussing important social factors and suggest that to reduce the risk of a misuse catastrophe due to aligned AGI, techniques such as robustness, AI control methods and especially good governance seem essential.

Multi-criteria Rank-based Aggregation for Explainable AI

Sujoy Chatterjee, Everton Romanzini Colombo, Marcos Medeiros Raimundo

Explainability is crucial for improving the transparency of black-box machine learning models. With the advancement of explanation methods such as LIME and SHAP, various XAI performance metrics have been developed to evaluate the quality of explanations. However, different explainers can provide contrasting explanations for the same prediction, introducing trade-offs across conflicting quality metrics. Although available aggregation approaches improve robustness, reducing explanations' variability, very limited research employed a multi-criteria decision-making approach. To address this gap, this paper introduces a multi-criteria rank-based weighted aggregation method that balances multiple quality metrics simultaneously to produce an ensemble of explanation models. Furthermore, we propose rank-based versions of existing XAI metrics (complexity, faithfulness and stability) to better evaluate ranked feature importance explanations. Extensive experiments on publicly available datasets demonstrate the robustness of the proposed model across these metrics. Comparative analyses of various multi-criteria decision-making and rank aggregation algorithms showed that TOPSIS and WSUM are the best candidates for this use case.

Understanding the reasoning behind deep learning model predictions is crucial in cheminformatics and drug discovery, where molecular design determines their properties. However, current evaluation frameworks for Explainable AI (XAI) in this domain often rely on artificial datasets or simplified tasks, employing data-derived metrics that fail to capture the complexity of real-world scenarios and lack a direct link to explanation faithfulness. To address this, we introduce B-XAIC, a novel benchmark constructed from real-world molecular data and diverse tasks with known ground-truth rationales for assigned labels. Through a comprehensive evaluation using B-XAIC, we reveal limitations of existing XAI methods for Graph Neural Networks (GNNs) in the molecular domain. This benchmark provides a valuable resource for gaining deeper insights into the faithfulness of XAI, facilitating the development of more reliable and interpretable models.

The introduction of the AI Act in the European Union presents the AI research and practice community with a set of new challenges related to compliance. While it is certain that AI practitioners will require additional guidance and tools to meet these requirements, previous research on toolkits that aim to translate the theory of AI ethics into development and deployment practice suggests that such resources suffer from multiple limitations. These limitations stem, in part, from the fact that the toolkits are either produced by industry-based teams or by academics whose work tends to be abstract and divorced from the realities of industry. In this paper, we discuss the challenge of developing an AI ethics toolkit for practitioners that helps them comply with new AI-focused regulation, but that also moves beyond mere compliance to consider broader socio-ethical questions throughout development and deployment. The toolkit was created through a cross-sectoral collaboration between an academic team based in the UK and an industry team in Italy. We outline the background and rationale for creating a pro-justice AI Act compliance toolkit, detail the process undertaken to develop it, and describe the collaboration and negotiation efforts that shaped its creation. We aim for the described process to serve as a blueprint for other teams navigating the challenges of academia-industry partnerships and aspiring to produce usable and meaningful AI ethics resources.

A Participatory Strategy for AI Ethics in Education and Rehabilitation grounded in the Capability Approach

Valeria Cesaroni, Eleonora Pasqua, Piercosma Bisconti +1

AI-based technologies have significant potential to enhance inclusive education and clinical-rehabilitative contexts for children with Special Educational Needs and Disabilities. AI can enhance learning experiences, empower students, and support both teachers and rehabilitators. However, their usage presents challenges that require a systemic-ecological vision, ethical considerations, and participatory research. Therefore, research and technological development must be rooted in a strong ethical-theoretical framework. The Capability Approach - a theoretical model of disability, human vulnerability, and inclusion - offers a more relevant perspective on functionality, effectiveness, and technological adequacy in inclusive learning environments. In this paper, we propose a participatory research strategy with different stakeholders through a case study on the ARTIS Project, which develops an AI-enriched interface to support children with text comprehension difficulties. Our research strategy integrates ethical, educational, clinical, and technological expertise in designing and implementing AI-based technologies for children's learning environments through focus groups and collaborative design sessions. We believe that this holistic approach to AI adoption in education can help bridge the gap between technological innovation and ethical responsibility.

What makes safety claims about general purpose AI systems such as large language models trustworthy? We show that rather than the capabilities of security tools such as alignment and red teaming procedures, it is security practices based on these tools that contributed to reconfiguring the image of AI safety and made the claims acceptable. After showing what causes the gap between the capabilities of security tools and the desired safety guarantees, we critically investigate how AI security practices attempt to fill the gap and identify several shortcomings in diversity and participation. We found that these security practices are part of securitization processes aiming to support (commercial) development of general purpose AI systems whose trustworthiness can only be imperfectly tested instead of guaranteed. We conclude by offering several improvements to the current AI security practices.

QuXAI: Explainers for Hybrid Quantum Machine Learning Models

Saikat Barua, Mostafizur Rahman, Shehenaz Khaled +3

The emergence of hybrid quantum-classical machine learning (HQML) models opens new horizons of computational intelligence but their fundamental complexity frequently leads to black box behavior that undermines transparency and reliability in their application. Although XAI for quantum systems still in its infancy, a major research gap is evident in robust global and local explainability approaches that are designed for HQML architectures that employ quantized feature encoding followed by classical learning. The gap is the focus of this work, which introduces QuXAI, an framework based upon Q-MEDLEY, an explainer for explaining feature importance in these hybrid systems. Our model entails the creation of HQML models incorporating quantum feature maps, the use of Q-MEDLEY, which combines feature based inferences, preserving the quantum transformation stage and visualizing the resulting attributions. Our result shows that Q-MEDLEY delineates influential classical aspects in HQML models, as well as separates their noise, and competes well against established XAI techniques in classical validation settings. Ablation studies more significantly expose the virtues of the composite structure used in Q-MEDLEY. The implications of this work are critically important, as it provides a route to improve the interpretability and reliability of HQML models, thus promoting greater confidence and being able to engage in safer and more responsible use of quantum-enhanced AI technology. Our code and experiments are open-sourced at: https://github.com/GitsSaikat/QuXAI

The integration of AI into daily life has generated considerable attention and excitement, while also raising concerns about automating algorithmic harms and re-entrenching existing social inequities. While the responsible deployment of trustworthy AI systems is a worthy goal, there are many possible ways to realize it, from policy and regulation to improved algorithm design and evaluation. In fact, since AI trains on social data, there is even a possibility for everyday users, citizens, or workers to directly steer the AI system's behavior through Algorithmic Collective Action, by deliberately modifying the data they share with a platform to drive its learning process in their favor. This paper considers how these grassroots efforts to influence AI interact with methods used by AI firms and governments to improve model trustworthiness. In particular, we focus on the setting where the AI firm deploys a differentially private model, motivated by the growing regulatory focus on privacy and data protection. We investigate how the use of Differentially Private Stochastic Gradient Descent (DP-SGD) affects the collective's ability to influence the learning process. Our findings show that while differential privacy protects individual data, it introduces challenges for effective algorithmic collective action. We establish this trade-off formally by characterizing lower bounds on the success of algorithmic collective action under differential privacy as a function of the collective's size and the firm's privacy parameters. We then verify these trends experimentally by simulating collective action during the training of deep neural network classifiers across several datasets. Finally, we perform a stylized economic analysis of privacy costs to integrate additional incentives, analyzing how utility and participation costs influence the formation of collectives under private training regimes.

As Natural Language Processing (NLP) models continue to evolve and become integral to high-stakes applications, ensuring their interpretability remains a critical challenge. Given the growing variety of explainability methods and diverse stakeholder requirements, frameworks that help stakeholders select appropriate explanations tailored to their specific use cases are increasingly important. To address this need, we introduce EvalxNLP, a Python framework for benchmarking state-of-the-art feature attribution methods for transformer-based NLP models. EvalxNLP integrates eight widely recognized explainability techniques from the Explainable AI (XAI) literature, enabling users to generate and evaluate explanations based on key properties such as faithfulness, plausibility, and complexity. Our framework also provides interactive, LLM-based textual explanations, facilitating user understanding of the generated explanations and evaluation outcomes. Human evaluation results indicate high user satisfaction with EvalxNLP, suggesting it is a promising framework for benchmarking explanation methods across diverse user groups. By offering a user-friendly and extensible platform, EvalxNLP aims at democratizing explainability tools and supporting the systematic comparison and advancement of XAI techniques in NLP.

Explanations as Bias Detectors: A Critical Study of Local Post-hoc XAI Methods for Fairness Exploration

Vasiliki Papanikou, Danae Pla Karidi, Evaggelia Pitoura +2

As Artificial Intelligence (AI) is increasingly used in areas that significantly impact human lives, concerns about fairness and transparency have grown, especially regarding their impact on protected groups. Recently, the intersection of explainability and fairness has emerged as an important area to promote responsible AI systems. This paper explores how explainability methods can be leveraged to detect and interpret unfairness. We propose a pipeline that integrates local post-hoc explanation methods to derive fairness-related insights. During the pipeline design, we identify and address critical questions arising from the use of explanations as bias detectors such as the relationship between distributive and procedural fairness, the effect of removing the protected attribute, the consistency and quality of results across different explanation methods, the impact of various aggregation strategies of local explanations on group fairness evaluations, and the overall trustworthiness of explanations as bias detectors. Our results show the potential of explanation methods used for fairness while highlighting the need to carefully consider the aforementioned critical aspects.