Despite the excelling performance of machine learning models, understanding their decisions remains a long-standing goal. Although commonly used attribution methods from explainable AI attempt to address this issue, they typically rely on associational rather than causal relationships. In this study, within the context of time series classification, we introduce a novel model-agnostic attribution method to assess the causal effect of concepts i.e., predefined segments within a time series, on classification outcomes. Our approach compares these causal attributions with closely related associational attributions, both theoretically and empirically. To estimate counterfactual outcomes, we use state-of-the-art diffusion models backed by state space models. We demonstrate the insights gained by our approach for a diverse set of qualitatively different time series classification tasks. Although causal and associational attributions might often share some similarities, in all cases they differ in important details, underscoring the risks associated with drawing causal conclusions from associational data alone. We believe that the proposed approach is also widely applicable in other domains to shed some light on the limits of associational attributions.

XAI gained considerable importance in recent years. Methods based on prototypical case-based reasoning have shown a promising improvement in explainability. However, these methods typically rely on additional post-hoc saliency techniques to explain the semantics of learned prototypes. Multiple critiques have been raised about the reliability and quality of such techniques. For this reason, we study the use of prominent image segmentation foundation models to improve the truthfulness of the mapping between embedding and input space. We aim to restrict the computation area of the saliency map to a predefined semantic image patch to reduce the uncertainty of such visualizations. To perceive the information of an entire image, we use the bounding box from each generated segmentation mask to crop the image. Each mask results in an individual input in our novel model architecture named ProtoMask. We conduct experiments on three popular fine-grained classification datasets with a wide set of metrics, providing a detailed overview on explainability characteristics. The comparison with other popular models demonstrates competitive performance and unique explainability features of our model. https://github.com/uos-sis/quanproto

Measuring the alignment between representations lets us understand similarities between the feature spaces of different models, such as Vision Transformers trained under diverse paradigms. However, traditional measures for representational alignment yield only scalar values that obscure how these spaces agree in terms of learned features. To address this, we combine alignment analysis with concept discovery, allowing a fine-grained breakdown of alignment into individual concepts. This approach reveals both universal concepts across models and each representation’s internal concept structure. We introduce a new definition of concepts as non-linear manifolds, hypothesizing they better capture the geometry of the feature space. A sanity check demonstrates the advantage of this manifold-based definition over linear baselines for concept-based alignment. Finally, our alignment analysis of four different ViTs shows that increased supervision tends to reduce semantic organization in learned representations.

MOTIVATION: We explored how explainable artificial intelligence (XAI) can help to shed light into the inner workings of neural networks for protein function prediction, by extending the widely used XAI method of integrated gradients such that latent representations inside of transformer models, which were finetuned to Gene Ontology term and Enzyme Commission number prediction, can be inspected too. RESULTS: The approach enabled us to identify amino acids in the sequences that the transformers pay particular attention to, and to show that these relevant sequence parts reflect expectations from biology and chemistry, both in the embedding layer and inside of the model, where we identified transformer heads with a statistically significant correspondence of attribution maps with ground truth sequence annotations (e.g. transmembrane regions, active sites) across many proteins. AVAILABILITY AND IMPLEMENTATION: Source code can be accessed at https://github.com/markuswenzel/xai-proteins.

Feature importance methods promise to provide a ranking of features according to importance for a given classification task. A wide range of methods exist but their rankings often disagree and they are inherently difficult to evaluate due to a lack of ground truth beyond synthetic datasets. In this work, we put feature importance methods to the test on real-world data in the domain of cardiology, where we try to distinguish three specific pathologies from healthy subjects based on ECG features comparing to features used in cardiologists' decision rules as ground truth. We found that the SHAP and LIME methods and Chi-squared test all worked well together with the native Random forest and Logistic regression feature rankings. Some methods gave inconsistent results, which included the Maximum Relevance Minimum Redundancy and Neighbourhood Component Analysis methods. The permutation-based methods generally performed quite poorly. A surprising result was found in the case of left bundle branch block, where T-wave morphology features were consistently identified as being important for diagnosis, but are not used by clinicians.

Deep learning has emerged as the preferred modeling approach for automatic ECG analysis. In this study, we investigate three elements aimed at improving the quantitative accuracy of such systems. These components consistently enhance performance beyond the existing state-of-the-art, which is predominantly based on convolutional models. Firstly, we explore more expressive architectures by exploiting structured state space models (SSMs). These models have shown promise in capturing long-term dependencies in time series data. By incorporating SSMs into our approach, we not only achieve better performance, but also gain insights into long-standing questions in the field. Specifically, for standard diagnostic tasks, we find no advantage in using higher sampling rates such as 500 Hz compared to 100 Hz. Similarly, extending the input size of the model beyond 3 seconds does not lead to significant improvements. Secondly, we demonstrate that self-supervised learning using contrastive predictive coding can further improve the performance of SSMs. By leveraging self-supervision, we enable the model to learn more robust and representative features, leading to improved analysis accuracy. Lastly, we depart from synthetic benchmarking scenarios and incorporate basic demographic metadata alongside the ECG signal as input. This inclusion of patient metadata departs from the conventional practice of relying solely on the signal itself. Remarkably, this addition consistently yields positive effects on predictive performance. We firmly believe that all three components should be considered when developing next-generation ECG analysis algorithms.

PredDiff is a model-agnostic, local attribution method that is firmly rooted in probability theory. Its simple intuition is to measure prediction changes while marginalizing features. In this work, we clarify properties of PredDiff and its close connection to Shapley values. We stress important differences between classification and regression, which require a specific treatment within both formalisms. We extend PredDiff by introducing a new, well-founded measure for interaction effects between arbitrary feature subsets. The study of interaction effects represents an inevitable step towards a comprehensive understanding of black-box models and is particularly important for science applications. Equipped with our novel interaction measure, PredDiff is a promising model-agnostic approach for obtaining reliable, numerically inexpensive and theoretically sound attributions.

Electrical impedance tomography (EIT) is a noninvasive imaging modality that allows a continuous assessment of changes in regional bioimpedance of different organs. One of its most common biomedical applications is monitoring regional ventilation distribution in critically ill patients treated in intensive care units. In this work, we put forward a proof-of-principle study that demonstrates how one can reconstruct synchronously measured respiratory or circulatory parameters from the EIT image sequence using a deep learning model trained in an end-to-end fashion. For this purpose, we devise an architecture with a convolutional feature extractor whose output is processed by a recurrent neural network. We demonstrate that one can accurately infer absolute volume, absolute flow, normalized airway pressure and within certain limitations even the normalized arterial blood pressure from the EIT signal alone, in a way that generalizes to unseen patients without prior calibration. As an outlook with direct clinical relevance, we furthermore demonstrate the feasibility of reconstructing the absolute transpulmonary pressure from a combination of EIT and absolute airway pressure, as a way to potentially replace the invasive measurement of esophageal pressure. With these results, we hope to stimulate further studies building on the framework put forward in this work.

Electrocardiography (ECG) is a very common, non-invasive diagnostic procedure and its interpretation is increasingly supported by algorithms. The progress in the field of automatic ECG analysis has up to now been hampered by a lack of appropriate datasets for training as well as a lack of well-defined evaluation procedures to ensure comparability of different algorithms. To alleviate these issues, we put forward first benchmarking results for the recently published, freely accessible clinical 12-lead ECG dataset PTB-XL, covering a variety of tasks from different ECG statement prediction tasks to age and sex prediction. Among the investigated deep-learning-based timeseries classification algorithms, we find that convolutional neural networks, in particular resnet- and inception-based architectures, show the strongest performance across all tasks. We find consistent results on the ICBEB2018 challenge ECG dataset and discuss prospects of transfer learning using classifiers pretrained on PTB-XL. These benchmarking results are complemented by deeper insights into the classification algorithm in terms of hidden stratification, model uncertainty and an exploratory interpretability analysis, which provide connecting points for future research on the dataset. Our results emphasize the prospects of deep-learning-based algorithms in the field of ECG analysis, not only in terms of quantitative accuracy but also in terms of clinically equally important further quality metrics such as uncertainty quantification and interpretability. With this resource, we aim to establish the PTB-XL dataset as a resource for structured benchmarking of ECG analysis algorithms and encourage other researchers in the field to join these efforts.

MOTIVATION: Inferring the properties of a protein from its amino acid sequence is one of the key problems in bioinformatics. Most state-of-the-art approaches for protein classification are tailored to single classification tasks and rely on handcrafted features, such as position-specific-scoring matrices from expensive database searches. We argue that this level of performance can be reached or even be surpassed by learning a task-agnostic representation once, using self-supervised language modeling, and transferring it to specific tasks by a simple fine-tuning step. RESULTS: We put forward a universal deep sequence model that is pre-trained on unlabeled protein sequences from Swiss-Prot and fine-tuned on protein classification tasks. We apply it to three prototypical tasks, namely enzyme class prediction, gene ontology prediction and remote homology and fold detection. The proposed method performs on par with state-of-the-art algorithms that were tailored to these specific tasks or, for two out of three tasks, even outperforms them. These results stress the possibility of inferring protein properties from the sequence alone and, on more general grounds, the prospects of modern natural language processing methods in omics. Moreover, we illustrate the prospects for explainable machine learning methods in this field by selected case studies. AVAILABILITY AND IMPLEMENTATION: Source code is available under https://github.com/nstrodt/UDSMProt. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Immunotherapy is a promising route towards personalized cancer treatment. A key algorithmic challenge in this process is to decide if a given peptide (neoepitope) binds with the major histocompatibility complex (MHC). This is an active area of research and there are many MHC binding prediction algorithms that can predict the MHC binding affinity for a given peptide to a high degree of accuracy. However, most of the state-of-the-art approaches make use of complicated training and model selection procedures, are restricted to peptides of a certain length and/or rely on heuristics. RESULTS: We put forward USMPep, a simple recurrent neural network that reaches state-of-the-art approaches on MHC class I binding prediction with a single, generic architecture and even a single set of hyperparameters both on IEDB benchmark datasets and on the very recent HPV dataset. Moreover, the algorithm is competitive for a single model trained from scratch, while ensembling multiple regressors and language model pretraining can still slightly improve the performance. The direct application of the approach to MHC class II binding prediction shows a solid performance despite of limited training data. CONCLUSIONS: We demonstrate that competitive performance in MHC binding affinity prediction can be reached with a standard architecture and training procedure without relying on any heuristics.

We investigate Early Hybrid Automatic Repeat reQuest (E-HARQ) feedback schemes enhanced by machine learning techniques as a path towards ultra-reliable and low-latency communication (URLLC). To this end, we propose machine learning methods to predict the outcome of the decoding process ahead of the end of the transmission. We discuss different input features and classification algorithms ranging from traditional methods to newly developed supervised autoencoders. These methods are evaluated based on their prospects of complying with the URLLC requirements of effective block error rates below 10-5at small latency overheads. We provide realistic performance estimates in a system model incorporating scheduling effects to demonstrate the feasibility of E-HARQ across different signal-to-noise ratios, subcode lengths, channel conditions and system loads, and show the benefit over regular HARQ and existing E-HARQ schemes without machine learning.