Since its emergence in the 1960s, Artificial Intelligence (AI) has grown to conquer many technology products and their fields of application. Machine learning, as a major part of the current AI solutions, can learn from the data and through experience to reach high performance on various tasks. This growing success of AI algorithms has led to a need for interpretability to understand opaque models such as deep neural networks. Various requirements have been raised from different domains, together with numerous tools to debug, justify outcomes, and establish the safety, fairness and reliability of the models. This variety of tasks has led to inconsistencies in the terminology with, for instance, terms such as interpretable, explainable and transparent being often used interchangeably in methodology papers. These words, however, convey different meanings and are “weighted" differently across domains, for example in the technical and social sciences. In this paper, we propose an overarching terminology of interpretability of AI systems that can be referred to by the technical developers as much as by the social sciences community to pursue clarity and efficiency in the definition of regulations for ethical and reliable AI development. We show how our taxonomy and definition of interpretable AI differ from the ones in previous research and how they apply with high versatility to several domains and use cases, proposing a—highly needed—standard for the communication among interdisciplinary areas of AI.

Deep Learning (DL) can predict biomarkers from cancer histopathology. Several clinically approved applications use this technology. Most approaches, however, predict categorical labels, whereas biomarkers are often continuous measurements. We hypothesize that regression-based DL outperforms classification-based DL. Therefore, we develop and evaluate a self-supervised attention-based weakly supervised regression method that predicts continuous biomarkers directly from 11,671 images of patients across nine cancer types. We test our method for multiple clinically and biologically relevant biomarkers: homologous recombination deficiency score, a clinically used pan-cancer biomarker, as well as markers of key biological processes in the tumor microenvironment. Using regression significantly enhances the accuracy of biomarker prediction, while also improving the predictions’ correspondence to regions of known clinical relevance over classification. In a large cohort of colorectal cancer patients, regression-based prediction scores provide a higher prognostic value than classification-based scores. Our open-source regression approach offers a promising alternative for continuous biomarker analysis in computational pathology.

Deep learning explainability is often reached by gradient-based approaches that attribute the network output to perturbations of the input pixels. However, the relevance of input pixels may be difficult to relate to relevant image features in some applications, e.g. diagnostic measures in medical imaging. The framework described in this paper shifts the attribution focus from pixel values to user-defined concepts. By checking if certain diagnostic measures are present in the learned representations, experts can explain and entrust the network output. Being post-hoc, our method does not alter the network training and can be easily plugged into the latest state-of-the-art convolutional networks. This paper presents the main components of the framework for attribution to concepts, in addition to the introduction of a spatial pooling operation on top of the feature maps to obtain a solid interpretability analysis. Furthermore, regularized regression is analyzed as a solution to the regression overfitting in high-dimensionality latent spaces. The versatility of the proposed approach is shown by experiments on two medical applications, namely histopathology and retinopathy, and on one non-medical task, the task of handwritten digit classification. The obtained explanations are in line with clinicians' guidelines and complementary to widely used visualization tools such as saliency maps.

The diffused practice of pre-training Convolutional Neural Networks (CNNs) on large natural image datasets such as ImageNet causes the automatic learning of invariance to object scale variations. This, however, can be detrimental in medical imaging, where pixel spacing has a known physical correspondence and size is crucial to the diagnosis, for example, the size of lesions, tumors or cell nuclei. In this paper, we use deep learning interpretability to identify at what intermediate layers such invariance is learned. We train and evaluate different regression models on the PASCAL-VOC (Pattern Analysis, Statistical modeling and ComputAtional Learning-Visual Object Classes) annotated data to (i) separate the effects of the closely related yet different notions of image size and object scale, (ii) quantify the presence of scale information in the CNN in terms of the layer-wise correlation between input scale and feature maps in InceptionV3 and ResNet50, and (iii) develop a pruning strategy that reduces the invariance to object scale of the learned features. Results indicate that scale information peaks at central CNN layers and drops close to the softmax, where the invariance is reached. Our pruning strategy uses this to obtain features that preserve scale information. We show that the pruning significantly improves the performance on medical tasks where scale is a relevant factor, for example for the regression of breast histology image magnification. These results show that the presence of scale information at intermediate layers legitimates transfer learning in applications that require scale covariance rather than invariance and that the performance on these tasks can be improved by pruning off the layers where the invariance is learned. All experiments are performed on publicly available data and the code is available on GitHub.

Trial-and-error approaches in chemistry generate abundant unsuccessful experiments, yet the potential of these so-called negative results remains largely underutilized. Here, we demonstrate that information from negative chemical reactions can be leveraged to improve reactivity-prediction models, offering advantages in scenarios with a limited volume of successful data. We extend the tuning of language models with reinforcement learning to the chemistry domain, training a transformer model for chemical reaction prediction. Our approach is evaluated using both a rigorously controlled dataset and a realistic high-throughput dataset comprising extensive reaction screenings across diverse catalysts sets and experimental conditions. The model achieves state-of-the-art performance by leveraging information from as few as 20 positive data points in the controlled dataset, supported by a negative dataset at least 40 times larger. Consistent results on both datasets demonstrate that, with an appropriate optimization strategy and the inclusion of unsuccessful experimental data, models can be effectively trained even when successful reactions are underrepresented.