Andreas Holzinger

Luca Longo, Mario Brcic, Federico Cabitza et al.

As systems based on opaque Artificial Intelligence (AI) continue to flourish in diverse real-world applications, understanding these black box models has become paramount. In response, Explainable AI (XAI) has emerged as a field of research with practical and ethical benefits across various domains. This paper not only highlights the advancements in XAI and its application in real-world scenarios but also addresses the ongoing challenges within XAI, emphasizing the need for broader perspectives and collaborative efforts. We bring together experts from diverse fields to identify open problems, striving to synchronize research agendas and accelerate XAI in practical applications. By fostering collaborative discussion and interdisciplinary cooperation, we aim to propel XAI forward, contributing to its continued success. Our goal is to put forward a comprehensive proposal for advancing XAI. To achieve this goal, we present a manifesto of 27 open problems categorized into nine categories. These challenges encapsulate the complexities and nuances of XAI and offer a road map for future research. For each problem, we provide promising research directions in the hope of harnessing the collective intelligence of interested stakeholders.

Przemyslaw Biecek, Luca Longo, Jianlong Zhou et al.

We argue that the AI community is now ready to move beyond benchmarking and consolidate scattered efforts in model analysis into a systematic discipline, a direction we term Model Science. Complex AI models now serve billions of users, yet our understanding of how they work lags far behind our ability to deploy them. Decades of benchmark-driven research have delivered remarkable progress: extensive leaderboards, a wide range of performance metrics, tracking capability gains across diverse tasks; yet this success has also revealed the limits of benchmarks as they tell us whether models perform but not why they succeed or fail, they miss critical failure modes, such as hallucinations or shortcuts. Precedents from established sciences point the way forward: cognitive science shows that understanding complex systems requires complementary levels of analysis; neuroscience demonstrates that deep study of single cases reveals what population studies miss; medicine teaches that specialised training must develop alongside research practice; and agriculture models how shared infrastructure and principles enable cumulative progress. These lessons inform three foundations for Model Science. First, we propose to consolidate research around four functional perspectives: Verify, Explore, Steer, and Refine that address complementary questions about model behaviour. Second, we discuss the required infrastructure for cumulative knowledge: catalogues of datasets, models and findings. Third, we highlight the need for deep analysis of individual model instances, not just model families, because single cases can reveal what population studies miss.

Javier Del Ser, Alejandro Barredo-Arrieta, Natalia Díaz-Rodríguez et al.

There is a broad consensus on the importance of deep learning models in tasks involving complex data. Often, an adequate understanding of these models is required when focusing on the transparency of decisions in human-critical applications. Besides other explainability techniques, trustworthiness can be achieved by using counterfactuals, like the way a human becomes familiar with an unknown process: by understanding the hypothetical circumstances under which the output changes. In this work we argue that automated counterfactual generation should regard several aspects of the produced adversarial instances, not only their adversarial capability. To this end, we present a novel framework for the generation of counterfactual examples which formulates its goal as a multi-objective optimization problem balancing three different objectives: 1) plausibility, i.e., the likeliness of the counterfactual of being possible as per the distribution of the input data; 2) intensity of the changes to the original input; and 3) adversarial power, namely, the variability of the model's output induced by the counterfactual. The framework departs from a target model to be audited and uses a Generative Adversarial Network to model the distribution of input data, together with a multi-objective solver for the discovery of counterfactuals balancing among these objectives. The utility of the framework is showcased over six classification tasks comprising image and three-dimensional data. The experiments verify that the framework unveils counterfactuals that comply with intuition, increasing the trustworthiness of the user, and leading to further insights, such as the detection of bias and data misrepresentation.

Bastian Pfeifer, Mateusz Krzyzinski, Hubert Baniecki et al.

Explainable AI (XAI) is an increasingly important area of machine learning research, which aims to make black-box models transparent and interpretable. In this paper, we propose a novel approach to XAI that uses the so-called counterfactual paths generated by conditional permutations of features. The algorithm measures feature importance by identifying sequential permutations of features that most influence changes in model predictions. It is particularly suitable for generating explanations based on counterfactual paths in knowledge graphs incorporating domain knowledge. Counterfactual paths introduce an additional graph dimension to current XAI methods in both explaining and visualizing black-box models. Experiments with synthetic and medical data demonstrate the practical applicability of our approach.

Hubert Baniecki, Maciej Chrabaszcz, Andreas Holzinger et al.

Evaluating explanations of image classifiers regarding ground truth, e.g. segmentation masks defined by human perception, primarily evaluates the quality of the models under consideration rather than the explanation methods themselves. Driven by this observation, we propose a framework for $\textit{jointly}$ evaluating the robustness of safety-critical systems that $\textit{combine}$ a deep neural network with an explanation method. These are increasingly used in real-world applications like medical image analysis or robotics. We introduce a fine-tuning procedure to (mis)align model$\unicode{x2013}$explanation pipelines with ground truth and use it to quantify the potential discrepancy between worst and best-case scenarios of human alignment. Experiments across various model architectures and post-hoc local interpretation methods provide insights into the robustness of vision transformers and the overall vulnerability of such AI systems to potential adversarial attacks.

Heimo Müller, Andreas Holzinger

Truth can mislead not because it is false but because delivering it through the wrong channel or authority to an audience with a different epistemic frame can harden misbelief rather than reduce it. Conventional fact checking assumes a shared epistemology that corrections from credible institutional sources will be received constructively across audiences. Evidence suggests instead that effectiveness declines and can reverse into backfire as the distance between source positioning and recipient epistemic orientation grows. We introduce Phase Aware Coherence Detection PACD which operationalises epistemic orientation from pre intervention assessments across institutional trust scientific epistemology conspiracy or anti elite openness and experiential or alternative epistemology. In a study of 45 participants we stratified individuals into three epistemic clusters and randomly assigned them to traditional fact checking phase aware coherence analysis or control before evaluating three claims 5G health effects urban trees and air quality and mRNA vaccine mechanism. Traditional fact checking shifted beliefs toward truth on average but produced substantial backfire and sharply reduced effectiveness among more sceptical participants. Phase aware coherence analysis produced little average change overall yet remained stable across epistemic clusters and substantially reduced backfire. On identity adjacent claims traditional fact checking increased confidence while reducing accuracy whereas phase aware framing avoided this harm. These findings motivate a shift from content centric to epistemology centric correction when truth misleads the problem is often a mismatch between audience orientation and the reference frame of the intervention.

Tessa Pulli, Jean-Baptiste Weibel, Peter Hönig et al.

6D object pose estimation plays a crucial role in scene understanding for applications such as robotics and augmented reality. To support the needs of ever-changing object sets in such context, modern zero-shot object pose estimators were developed to not require object-specific training but only rely on CAD models. Such models are hard to obtain once deployed, and a continuously changing and growing set of objects makes it harder to reliably identify the instance model of interest. To address this challenge, we introduce an Open-Set CAD Retrieval from a Language Prompt and a Single Image (OSCAR), a novel training-free method that retrieves a matching object model from an unlabeled 3D object database. During onboarding, OSCAR generates multi-view renderings of database models and annotates them with descriptive captions using an image captioning model. At inference, GroundedSAM detects the queried object in the input image, and multi-modal embeddings are computed for both the Region-of-Interest and the database captions. OSCAR employs a two-stage retrieval: text-based filtering using CLIP identifies candidate models, followed by image-based refinement using DINOv2 to select the most visually similar object. In our experiments we demonstrate that OSCAR outperforms all state-of-the-art methods on the cross-domain 3D model retrieval benchmark MI3DOR. Furthermore, we demonstrate OSCAR's direct applicability in automating object model sourcing for 6D object pose estimation. We propose using the most similar object model for pose estimation if the exact instance is not available and show that OSCAR achieves an average precision of 90.48\% during object retrieval on the YCB-V object dataset. Moreover, we demonstrate that the most similar object model can be utilized for pose estimation using Megapose achieving better results than a reconstruction-based approach.

Javier Del Ser, Jesus L. Lobo, Heimo Müller et al.

World Models help Artificial Intelligence (AI) predict outcomes, reason about its environment, and guide decision-making. While widely used in reinforcement learning, they lack the structured, adaptive representations that even young children intuitively develop. Advancing beyond pattern recognition requires dynamic, interpretable frameworks inspired by Piaget's cognitive development theory. We highlight six key research areas -- physics-informed learning, neurosymbolic learning, continual learning, causal inference, human-in-the-loop AI, and responsible AI -- as essential for enabling true reasoning in AI. By integrating statistical learning with advances in these areas, AI can evolve from pattern recognition to genuine understanding, adaptation and reasoning capabilities.

Gernot Fiala, Markus Plass, Robert Harb et al.

A Whole Slide Image (WSI) is a high-resolution digital image created by scanning an entire glass slide containing a biological specimen, such as tissue sections or cell samples, at multiple magnifications. These images can be viewed, analyzed, shared digitally, and are used today for Artificial Intelligence (AI) algorithm development. WSIs are used in a variety of fields, including pathology for diagnosing diseases and oncology for cancer research. They are also utilized in neurology, veterinary medicine, hematology, microbiology, dermatology, pharmacology, toxicology, immunology, and forensic science. When assembling cohorts for the training or validation of an AI algorithm, it is essential to know what is present on such a WSI. However, there is currently no standard for this metadata, so such selection has mainly been done through manual inspection, which is not suitable for large collections with several million objects. We propose a general framework to generate a 2D index map for WSI and a profiling mechanism for specific application domains. We demonstrate this approach in the field of clinical pathology, using common syntax and semantics to achieve interoperability between different catalogs. Our approach augments each WSI collection with a detailed tissue map that provides fine-grained information about the WSI content. The tissue map is organized into three layers: source, tissue type, and pathological alterations, with each layer assigning segments of the WSI to specific classes. We illustrate the advantages and applicability of the proposed standard through specific examples in WSI catalogs, Machine Learning (ML), and graph-based WSI representations.

Jianlong Zhou, Heimo Müller, Andreas Holzinger et al.

Large language models, e.g. ChatGPT are currently contributing enormously to make artificial intelligence even more popular, especially among the general population. However, such chatbot models were developed as tools to support natural language communication between humans. Problematically, it is very much a ``statistical correlation machine" (correlation instead of causality) and there are indeed ethical concerns associated with the use of AI language models such as ChatGPT, such as Bias, Privacy, and Abuse. This paper highlights specific ethical concerns on ChatGPT and articulates key challenges when ChatGPT is used in various applications. Practical commandments for different stakeholders of ChatGPT are also proposed that can serve as checklist guidelines for those applying ChatGPT in their applications. These commandment examples are expected to motivate the ethical use of ChatGPT.

Adrien Bennetot, Ivan Donadello, Ayoub El Qadi et al.

Last years have been characterized by an upsurge of opaque automatic decision support systems, such as Deep Neural Networks (DNNs). Although they have great generalization and prediction skills, their functioning does not allow obtaining detailed explanations of their behaviour. As opaque machine learning models are increasingly being employed to make important predictions in critical environments, the danger is to create and use decisions that are not justifiable or legitimate. Therefore, there is a general agreement on the importance of endowing machine learning models with explainability. EXplainable Artificial Intelligence (XAI) techniques can serve to verify and certify model outputs and enhance them with desirable notions such as trustworthiness, accountability, transparency and fairness. This guide is meant to be the go-to handbook for any audience with a computer science background aiming at getting intuitive insights on machine learning models, accompanied with straight, fast, and intuitive explanations out of the box. This article aims to fill the lack of compelling XAI guide by applying XAI techniques in their particular day-to-day models, datasets and use-cases. Figure 1 acts as a flowchart/map for the reader and should help him to find the ideal method to use according to his type of data. In each chapter, the reader will find a description of the proposed method as well as an example of use on a Biomedical application and a Python notebook. It can be easily modified in order to be applied to specific applications.

Bastian Pfeifer, Hubert Baniecki, Anna Saranti et al.

Machine learning methods can detect complex relationships between variables, but usually do not exploit domain knowledge. This is a limitation because in many scientific disciplines, such as systems biology, domain knowledge is available in the form of graphs or networks, and its use can improve model performance. We need network-based algorithms that are versatile and applicable in many research areas. In this work, we demonstrate subnetwork detection based on multi-modal node features using a novel Greedy Decision Forest with inherent interpretability. The latter will be a crucial factor to retain experts and gain their trust in such algorithms. To demonstrate a concrete application example, we focus on bioinformatics, systems biology and particularly biomedicine, but the presented methodology is applicable in many other domains as well. Systems biology is a good example of a field in which statistical data-driven machine learning enables the analysis of large amounts of multi-modal biomedical data. This is important to reach the future goal of precision medicine, where the complexity of patients is modeled on a system level to best tailor medical decisions, health practices and therapies to the individual patient. Our proposed approach can help to uncover disease-causing network modules from multi-omics data to better understand complex diseases such as cancer.

Julian Matschinske, Julian Späth, Reza Nasirigerdeh et al.

Machine Learning (ML) and Artificial Intelligence (AI) have shown promising results in many areas and are driven by the increasing amount of available data. However, this data is often distributed across different institutions and cannot be shared due to privacy concerns. Privacy-preserving methods, such as Federated Learning (FL), allow for training ML models without sharing sensitive data, but their implementation is time-consuming and requires advanced programming skills. Here, we present the FeatureCloud AI Store for FL as an all-in-one platform for biomedical research and other applications. It removes large parts of this complexity for developers and end-users by providing an extensible AI Store with a collection of ready-to-use apps. We show that the federated apps produce similar results to centralized ML, scale well for a typical number of collaborators and can be combined with Secure Multiparty Computation (SMPC), thereby making FL algorithms safely and easily applicable in biomedical and clinical environments.

André M. Carrington, Douglas G. Manuel, Paul W. Fieguth et al.

Optimal performance is critical for decision-making tasks from medicine to autonomous driving, however common performance measures may be too general or too specific. For binary classifiers, diagnostic tests or prognosis at a timepoint, measures such as the area under the receiver operating characteristic curve, or the area under the precision recall curve, are too general because they include unrealistic decision thresholds. On the other hand, measures such as accuracy, sensitivity or the F1 score are measures at a single threshold that reflect an individual single probability or predicted risk, rather than a range of individuals or risk. We propose a method in between, deep ROC analysis, that examines groups of probabilities or predicted risks for more insightful analysis. We translate esoteric measures into familiar terms: AUC and the normalized concordant partial AUC are balanced average accuracy (a new finding); the normalized partial AUC is average sensitivity; and the normalized horizontal partial AUC is average specificity. Along with post-test measures, we provide a method that can improve model selection in some cases and provide interpretation and assurance for patients in each risk group. We demonstrate deep ROC analysis in two case studies and provide a toolkit in Python.

Andreas Holzinger, Anna Saranti, Heimo Mueller

Machine intelligence is very successful at standard recognition tasks when having high-quality training data. There is still a significant gap between machine-level pattern recognition and human-level concept learning. Humans can learn under uncertainty from only a few examples and generalize these concepts to solve new problems. The growing interest in explainable machine intelligence, requires experimental environments and diagnostic tests to analyze weaknesses in existing approaches to drive progress in the field. In this paper, we discuss existing diagnostic tests and test data sets such as CLEVR, CLEVERER, CLOSURE, CURI, Bongard-LOGO, V-PROM, and present our own experimental environment: The KANDINSKYPatterns, named after the Russian artist Wassily Kandinksy, who made theoretical contributions to compositivity, i.e. that all perceptions consist of geometrically elementary individual components. This was experimentally proven by Hubel &Wiesel in the 1960s and became the basis for machine learning approaches such as the Neocognitron and the even later Deep Learning. While KANDINSKYPatterns have computationally controllable properties on the one hand, bringing ground truth, they are also easily distinguishable by human observers, i.e., controlled patterns can be described by both humans and algorithms, making them another important contribution to international research in machine intelligence.

Ellery Wulczyn, Kunal Nagpal, Matthew Symonds et al.

Gleason grading of prostate cancer is an important prognostic factor but suffers from poor reproducibility, particularly among non-subspecialist pathologists. Although artificial intelligence (A.I.) tools have demonstrated Gleason grading on-par with expert pathologists, it remains an open question whether A.I. grading translates to better prognostication. In this study, we developed a system to predict prostate-cancer specific mortality via A.I.-based Gleason grading and subsequently evaluated its ability to risk-stratify patients on an independent retrospective cohort of 2,807 prostatectomy cases from a single European center with 5-25 years of follow-up (median: 13, interquartile range 9-17). The A.I.'s risk scores produced a C-index of 0.84 (95%CI 0.80-0.87) for prostate cancer-specific mortality. Upon discretizing these risk scores into risk groups analogous to pathologist Grade Groups (GG), the A.I. had a C-index of 0.82 (95%CI 0.78-0.85). On the subset of cases with a GG in the original pathology report (n=1,517), the A.I.'s C-indices were 0.87 and 0.85 for continuous and discrete grading, respectively, compared to 0.79 (95%CI 0.71-0.86) for GG obtained from the reports. These represent improvements of 0.08 (95%CI 0.01-0.15) and 0.07 (95%CI 0.00-0.14) respectively. Our results suggest that A.I.-based Gleason grading can lead to effective risk-stratification and warrants further evaluation for improving disease management.

Reihaneh Torkzadehmahani, Reza Nasirigerdeh, David B. Blumenthal et al.

Artificial intelligence (AI) has been successfully applied in numerous scientific domains. In biomedicine, AI has already shown tremendous potential, e.g. in the interpretation of next-generation sequencing data and in the design of clinical decision support systems. However, training an AI model on sensitive data raises concerns about the privacy of individual participants. For example, summary statistics of a genome-wide association study can be used to determine the presence or absence of an individual in a given dataset. This considerable privacy risk has led to restrictions in accessing genomic and other biomedical data, which is detrimental for collaborative research and impedes scientific progress. Hence, there has been a substantial effort to develop AI methods that can learn from sensitive data while protecting individuals' privacy. This paper provides a structured overview of recent advances in privacy-preserving AI techniques in biomedicine. It places the most important state-of-the-art approaches within a unified taxonomy and discusses their strengths, limitations, and open problems. As the most promising direction, we suggest combining federated machine learning as a more scalable approach with other additional privacy preserving techniques. This would allow to merge the advantages to provide privacy guarantees in a distributed way for biomedical applications. Nonetheless, more research is necessary as hybrid approaches pose new challenges such as additional network or computation overhead.

Andreas Holzinger, André Carrington, Heimo Müller

Recent success in Artificial Intelligence (AI) and Machine Learning (ML) allow problem solving automatically without any human intervention. Autonomous approaches can be very convenient. However, in certain domains, e.g., in the medical domain, it is necessary to enable a domain expert to understand, why an algorithm came up with a certain result. Consequently, the field of Explainable AI (xAI) rapidly gained interest worldwide in various domains, particularly in medicine. Explainable AI studies transparency and traceability of opaque AI/ML and there are already a huge variety of methods. For example with layer-wise relevance propagation relevant parts of inputs to, and representations in, a neural network which caused a result, can be highlighted. This is a first important step to ensure that end users, e.g., medical professionals, assume responsibility for decision making with AI/ML and of interest to professionals and regulators. Interactive ML adds the component of human expertise to AI/ML processes by enabling them to re-enact and retrace AI/ML results, e.g. let them check it for plausibility. This requires new human-AI interfaces for explainable AI. In order to build effective and efficient interactive human-AI interfaces we have to deal with the question of how to evaluate the quality of explanations given by an explainable AI system. In this paper we introduce our System Causability Scale (SCS) to measure the quality of explanations. It is based on our notion of Causability (Holzinger et al., 2019) combined with concepts adapted from a widely accepted usability scale.

Marcus D. Bloice, Peter M. Roth, Andreas Holzinger

In this paper a neural network is trained to perform simple arithmetic using images of concatenated handwritten digit pairs. A convolutional neural network was trained with images consisting of two side-by-side handwritten digits, where the image's label is the summation of the two digits contained in the combined image. Crucially, the network was tested on permutation pairs that were not present during training in an effort to see if the network could learn the task of addition, as opposed to simply mapping images to labels. A dataset was generated for all possible permutation pairs of length 2 for the digits 0-9 using MNIST as a basis for the images, with one thousand samples generated for each permutation pair. For testing the network, samples generated from previously unseen permutation pairs were fed into the trained network, and its predictions measured. Results were encouraging, with the network achieving an accuracy of over 90% on some permutation train/test splits. This suggests that the network learned at first digit recognition, and subsequently the further task of addition based on the two recognised digits. As far as the authors are aware, no previous work has concentrated on learning a mathematical operation in this way.

Marcus D. Bloice, Peter M. Roth, Andreas Holzinger

In this paper we propose a new augmentation technique, called patch augmentation, that, in our experiments, improves model accuracy and makes networks more robust to adversarial attacks. In brief, this data-independent approach creates new image data based on image/label pairs, where a patch from one of the two images in the pair is superimposed on to the other image, creating a new augmented sample. The new image's label is a linear combination of the image pair's corresponding labels. Initial experiments show a several percentage point increase in accuracy on CIFAR-10, from a baseline of approximately 81% to 89%. CIFAR-100 sees larger improvements still, from a baseline of 52% to 68% accuracy. Networks trained using patch augmentation are also more robust to adversarial attacks, which we demonstrate using the Fast Gradient Sign Method.

Heimo Mueller, Andreas Holzinger

Kandinsky Figures and Kandinsky Patterns are mathematically describable, simple self-contained hence controllable test data sets for the development, validation and training of explainability in artificial intelligence. Whilst Kandinsky Patterns have these computationally manageable properties, they are at the same time easily distinguishable from human observers. Consequently, controlled patterns can be described by both humans and computers. We define a Kandinsky Pattern as a set of Kandinsky Figures, where for each figure an "infallible authority" defines that the figure belongs to the Kandinsky Pattern. With this simple principle we build training and validation data sets for automatic interpretability and context learning. In this paper we describe the basic idea and some underlying principles of Kandinsky Patterns and provide a Github repository to invite the international machine learning research community to a challenge to experiment with our Kandinsky Patterns to expand and thus make progress in the field of explainable AI and to contribute to the upcoming field of explainability and causability.

Deepika Singh, Erinc Merdivan, Ismini Psychoula et al.

Human activity recognition using smart home sensors is one of the bases of ubiquitous computing in smart environments and a topic undergoing intense research in the field of ambient assisted living. The increasingly large amount of data sets calls for machine learning methods. In this paper, we introduce a deep learning model that learns to classify human activities without using any prior knowledge. For this purpose, a Long Short Term Memory (LSTM) Recurrent Neural Network was applied to three real world smart home datasets. The results of these experiments show that the proposed approach outperforms the existing ones in terms of accuracy and performance.

Ismini Psychoula, Erinc Merdivan, Deepika Singh et al.

In the era of Internet of Things (IoT) technologies the potential for privacy invasion is becoming a major concern especially in regards to healthcare data and Ambient Assisted Living (AAL) environments. Systems that offer AAL technologies make extensive use of personal data in order to provide services that are context-aware and personalized. This makes privacy preservation a very important issue especially since the users are not always aware of the privacy risks they could face. A lot of progress has been made in the deep learning field, however, there has been lack of research on privacy preservation of sensitive personal data with the use of deep learning. In this paper we focus on a Long Short Term Memory (LSTM) Encoder-Decoder, which is a principal component of deep learning, and propose a new encoding technique that allows the creation of different AAL data views, depending on the access level of the end user and the information they require access to. The efficiency and effectiveness of the proposed method are demonstrated with experiments on a simulated AAL dataset. Qualitatively, we show that the proposed model learns privacy operations such as disclosure, deletion and generalization and can perform encoding and decoding of the data with almost perfect recovery.

Bernd Malle, Nicola Giuliani, Peter Kieseberg et al.

AI applications pose increasing demands on performance, so it is not surprising that the era of client-side distributed software is becoming important. On top of many AI applications already using mobile hardware, and even browsers for computationally demanding AI applications, we are already witnessing the emergence of client-side (federated) machine learning algorithms, driven by the interests of large corporations and startups alike. Apart from mathematical and algorithmic concerns, this trend especially demands new levels of computational efficiency from client environments. Consequently, this paper deals with the question of state-of-the-art performance by presenting a comparison study between native code and different browser-based implementations: JavaScript, ASM.js as well as WebAssembly on a representative mix of algorithms. Our results show that current efforts in runtime optimization push the boundaries well towards (and even beyond) native binary performance. We analyze the results obtained and speculate on the reasons behind some surprises, rounding the paper off by outlining future possibilities as well as some of our own research efforts.

Andreas Holzinger, Chris Biemann, Constantinos S. Pattichis et al.

Artificial intelligence (AI) generally and machine learning (ML) specifically demonstrate impressive practical success in many different application domains, e.g. in autonomous driving, speech recognition, or recommender systems. Deep learning approaches, trained on extremely large data sets or using reinforcement learning methods have even exceeded human performance in visual tasks, particularly on playing games such as Atari, or mastering the game of Go. Even in the medical domain there are remarkable results. The central problem of such models is that they are regarded as black-box models and even if we understand the underlying mathematical principles, they lack an explicit declarative knowledge representation, hence have difficulty in generating the underlying explanatory structures. This calls for systems enabling to make decisions transparent, understandable and explainable. A huge motivation for our approach are rising legal and privacy aspects. The new European General Data Protection Regulation entering into force on May 25th 2018, will make black-box approaches difficult to use in business. This does not imply a ban on automatic learning approaches or an obligation to explain everything all the time, however, there must be a possibility to make the results re-traceable on demand. In this paper we outline some of our research topics in the context of the relatively new area of explainable-AI with a focus on the application in medicine, which is a very special domain. This is due to the fact that medical professionals are working mostly with distributed heterogeneous and complex sources of data. In this paper we concentrate on three sources: images, *omics data and text. We argue that research in explainable-AI would generally help to facilitate the implementation of AI/ML in the medical domain, and specifically help to facilitate transparency and trust.

Andreas Holzinger, Bernd Malle, Peter Kieseberg et al.

Digital pathology is not only one of the most promising fields of diagnostic medicine, but at the same time a hot topic for fundamental research. Digital pathology is not just the transfer of histopathological slides into digital representations. The combination of different data sources (images, patient records, and *omics data) together with current advances in artificial intelligence/machine learning enable to make novel information accessible and quantifiable to a human expert, which is not yet available and not exploited in current medical settings. The grand goal is to reach a level of usable intelligence to understand the data in the context of an application task, thereby making machine decisions transparent, interpretable and explainable. The foundation of such an "augmented pathologist" needs an integrated approach: While machine learning algorithms require many thousands of training examples, a human expert is often confronted with only a few data points. Interestingly, humans can learn from such few examples and are able to instantly interpret complex patterns. Consequently, the grand goal is to combine the possibilities of artificial intelligence with human intelligence and to find a well-suited balance between them to enable what neither of them could do on their own. This can raise the quality of education, diagnosis, prognosis and prediction of cancer and other diseases. In this paper we describe some (incomplete) research issues which we believe should be addressed in an integrated and concerted effort for paving the way towards the augmented pathologist.

Marcus D. Bloice, Christof Stocker, Andreas Holzinger

The generation of artificial data based on existing observations, known as data augmentation, is a technique used in machine learning to improve model accuracy, generalisation, and to control overfitting. Augmentor is a software package, available in both Python and Julia versions, that provides a high level API for the expansion of image data using a stochastic, pipeline-based approach which effectively allows for images to be sampled from a distribution of augmented images at runtime. Augmentor provides methods for most standard augmentation practices as well as several advanced features such as label-preserving, randomised elastic distortions, and provides many helper functions for typical augmentation tasks used in machine learning.

Andreas Holzinger, Markus Plass, Katharina Holzinger et al.

The goal of Machine Learning to automatically learn from data, extract knowledge and to make decisions without any human intervention. Such automatic (aML) approaches show impressive success. Recent results even demonstrate intriguingly that deep learning applied for automatic classification of skin lesions is on par with the performance of dermatologists, yet outperforms the average. As human perception is inherently limited, such approaches can discover patterns, e.g. that two objects are similar, in arbitrarily high-dimensional spaces what no human is able to do. Humans can deal only with limited amounts of data, whilst big data is beneficial for aML; however, in health informatics, we are often confronted with a small number of data sets, where aML suffer of insufficient training samples and many problems are computationally hard. Here, interactive machine learning (iML) may be of help, where a human-in-the-loop contributes to reduce the complexity of NP-hard problems. A further motivation for iML is that standard black-box approaches lack transparency, hence do not foster trust and acceptance of ML among end-users. Rising legal and privacy aspects, e.g. with the new European General Data Protection Regulations, make black-box approaches difficult to use, because they often are not able to explain why a decision has been made. In this paper, we present some experiments to demonstrate the effectiveness of the human-in-the-loop approach, particularly in opening the black-box to a glass-box and thus enabling a human directly to interact with an learning algorithm. We selected the Ant Colony Optimization framework, and applied it on the Traveling Salesman Problem, which is a good example, due to its relevance for health informatics, e.g. for the study of protein folding. From studies of how humans extract so much from so little data, fundamental ML-research also may benefit.

Irina Kuznetsova, Yuliya V Karpievitch, Aleksandra Filipovska et al.

In biological research machine learning algorithms are part of nearly every analytical process. They are used to identify new insights into biological phenomena, interpret data, provide molecular diagnosis for diseases and develop personalized medicine that will enable future treatments of diseases. In this paper we (1) illustrate the importance of machine learning in the analysis of large scale sequencing data, (2) present an illustrative standardized workflow of the analysis process, (3) perform a Differential Expression (DE) analysis of a publicly available RNA sequencing (RNASeq) data set to demonstrate the capabilities of various algorithms at each step of the workflow, and (4) show a machine learning solution in improving the computing time, storage requirements, and minimize utilization of computer memory in analyses of RNA-Seq datasets. The source code of the analysis pipeline and associated scripts are presented in the paper appendix to allow replication of experiments.