MSc.

Ricards Marcinkevics

PhD Student

E-Mail
ricardsm@inf.ethz.ch
Phone
+41 44 632 07 98
Address
Department of Computer Science
CAB G 33.2
Universitätstr. 6
CH – 8092 Zurich, Switzerland
Room
CAB G 33.2

I completed my master's in Statistics in 2019 at the Department of Mathematics, ETH, where I focused on Machine Learning and Biostatistics.

At the moment, I am broadly interested in interpretable and explainable machine learning. In particular, I would like to understand what are the inductive biases for neural networks that may render the model interpretable in specific use-cases and how such inductive biases may be incorporated into the model? Moreover, how can we leverage interpretations and explanations to obtain actionable insights about the data or the model itself, for instance, to perform scientific discovery or make our classifiers fairer or more robust? From the application perspective, I work on time series and survival analysis and enjoy participating in interdisciplinary projects and leveraging ML methods to analyse biomedical data.

Further details can be found on my webpage.

Abstract

Recently, interpretable machine learning has re-explored concept bottleneck models (CBM), comprising step-by-step prediction of the high-level concepts from the raw features and the target variable from the predicted concepts. A compelling advantage of this model class is the user's ability to intervene on the predicted concept values, affecting the model's downstream output. In this work, we introduce a method to perform such concept-based interventions on already-trained neural networks, which are not interpretable by design, given an annotated validation set. Furthermore, we formalise the model's intervenability as a measure of the effectiveness of concept-based interventions and leverage this definition to fine-tune black-box models. Empirically, we explore the intervenability of black-box classifiers on synthetic tabular and natural image benchmarks. We demonstrate that fine-tuning improves intervention effectiveness and often yields better-calibrated predictions. To showcase the practical utility of the proposed techniques, we apply them to deep chest X-ray classifiers and show that fine-tuned black boxes can be as intervenable and more performant than CBMs.

Authors

Ricards Marcinkevics, Sonia Laguna, Moritz Vandenhirtz, Julia E. Vogt

Submitted

Arxiv

Date

24.01.2024

Link

Abstract

Appendicitis is among the most frequent reasons for pediatric abdominal surgeries. Previous decision support systems for appendicitis have focused on clinical, laboratory, scoring, and computed tomography data and have ignored abdominal ultrasound, despite its noninvasive nature and widespread availability. In this work, we present interpretable machine learning models for predicting the diagnosis, management and severity of suspected appendicitis using ultrasound images. Our approach utilizes concept bottleneck models (CBM) that facilitate interpretation and interaction with high-level concepts understandable to clinicians. Furthermore, we extend CBMs to prediction problems with multiple views and incomplete concept sets. Our models were trained on a dataset comprising 579 pediatric patients with 1709 ultrasound images accompanied by clinical and laboratory data. Results show that our proposed method enables clinicians to utilize a human-understandable and intervenable predictive model without compromising performance or requiring time-consuming image annotation when deployed. For predicting the diagnosis, the extended multiview CBM attained an AUROC of 0.80 and an AUPR of 0.92, performing comparably to similar black-box neural networks trained and tested on the same dataset.

Authors

Ricards Marcinkevics*, Patricia Reis Wolfertstetter*, Ugne Klimiene*, Kieran Chin-Cheong, Alyssia Paschke, Julia Zerres, Markus Denzinger, David Niederberger, Sven Wellmann, Ece Özkan Elsen, Christian Knorr, Julia E. Vogt
* denotes shared first authorship, denotes shared last authorship

Submitted

Medical Image Analysis

Date

01.01.2024

LinkDOICode

Abstract

Recently, interpretable machine learning has re-explored concept bottleneck models (CBM), comprising step-by-step prediction of the high-level concepts from the raw features and the target variable from the predicted concepts. A compelling advantage of this model class is the user's ability to intervene on the predicted concept values, consequently affecting the model's downstream output. In this work, we introduce a method to perform such concept-based interventions on already-trained neural networks, which are not interpretable by design. Furthermore, we formalise the model's intervenability as a measure of the effectiveness of concept-based interventions and leverage this definition to fine-tune black-box models. Empirically, we explore the intervenability of black-box classifiers on synthetic tabular and natural image benchmarks. We demonstrate that fine-tuning improves intervention effectiveness and often yields better-calibrated predictions. To showcase the practical utility of the proposed techniques, we apply them to chest X-ray classifiers and show that fine-tuned black boxes can be as intervenable and more performant than CBMs.

Authors

Ricards Marcinkevics, Sonia Laguna, Moritz Vandenhirtz, Julia E. Vogt

Submitted

XAI in Action: Past, Present, and Future Applications, NeurIPS 2023

Date

16.12.2023

Link

Abstract

Chronic obstructive pulmonary disease (COPD) is a significant public health issue, affecting more than 100 million people worldwide. Remote patient monitoring has shown great promise in the efficient management of patients with chronic diseases. This work presents the analysis of the data from a monitoring system developed to track COPD symptoms alongside patients’ self-reports. In particular, we investigate the assessment of COPD severity using multisensory home-monitoring device data acquired from 30 patients over a period of three months. We describe a comprehensive data pre-processing and feature engineering pipeline for multimodal data from the remote home-monitoring of COPD patients. We develop and validate predictive models forecasting i) the absolute and ii) differenced COPD Assessment Test (CAT) scores based on the multisensory data. The best obtained models achieve Pearson’s correlation coefficient of 0.93 and 0.37 for absolute and differenced CAT scores. In addition, we investigate the importance of individual sensor modalities for predicting CAT scores using group sparse regularization techniques. Our results suggest that feature groups indicative of the patient’s general condition, such as static medical and physiological information, date, spirometer, and air quality, are crucial for predicting the absolute CAT score. For predicting changes in CAT scores, sleep and physical activity features are most important, alongside the previous CAT score value. Our analysis demonstrates the potential of remote patient monitoring for COPD management and investigates which sensor modalities are most indicative of COPD severity as assessed by the CAT score. Our findings contribute to the development of effective and data-driven COPD management strategies.

Authors

Zixuan Xiao, Michal Muszynski, Ricards Marcinkevics, Lukas Zimmerli, Adam D. Ivankay, Dario Kohlbrenner, Manuel Kuhn, Yves Nordmann, Ulrich Muehlner, Christian Clarenbach, Julia E. Vogt, Thomas Brunschwiler

Submitted

25th ACM International Conference on Multimodal Interaction, ICMI'23

Date

09.10.2023

LinkDOI

Abstract

Appendicitis is among the most frequent reasons for pediatric abdominal surgeries. With recent advances in machine learning, data-driven decision support could help clinicians diagnose and manage patients while reducing the number of non-critical surgeries. However, previous decision support systems for appendicitis have focused on clinical, laboratory, scoring, and computed tomography data and have ignored the use of abdominal ultrasound, despite its noninvasive nature and widespread availability. In this work, we present interpretable machine learning models for predicting the diagnosis, management and severity of suspected appendicitis using ultrasound images. To this end, our approach utilizes concept bottleneck models (CBM) that facilitate interpretation and interaction with high-level concepts that are understandable to clinicians. Furthermore, we extend CBMs to prediction problems with multiple views and incomplete concept sets. Our models were trained on a dataset comprising 579 pediatric patients with 1709 ultrasound images accompanied by clinical and laboratory data. Results show that our proposed method enables clinicians to utilize a human-understandable and intervenable predictive model without compromising performance or requiring time-consuming image annotation when deployed.

Authors

Ricards Marcinkevics, Patricia Reis Wolfertstetter, Ugne Klimiene, Kieran Chin-Cheong, Alyssia Paschke, Julia Zerres, Markus Denzinger, David Niederberger, Sven Wellmann, Ece Özkan Elsen, Christian Knorr, Julia E. Vogt

Submitted

Workshop on Machine Learning for Multimodal Healthcare Data, Co-located with ICML 2023

Date

29.07.2023

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces B and T cell responses, contributing to virus neutralization. In a cohort of 2,911 young adults, we identified 65 individuals who had an asymptomatic or mildly symptomatic SARS-CoV-2 infection and characterized their humoral and T cell responses to the Spike (S), Nucleocapsid (N) and Membrane (M) proteins. We found that previous infection induced CD4 T cells that vigorously responded to pools of peptides derived from the S and N proteins. By using statistical and machine learning models, we observed that the T cell response highly correlated with a compound titer of antibodies against the Receptor Binding Domain (RBD), S and N. However, while serum antibodies decayed over time, the cellular phenotype of these individuals remained stable over four months. Our computational analysis demonstrates that in young adults, asymptomatic and paucisymptomatic SARS-CoV-2 infections can induce robust and long-lasting CD4 T cell responses that exhibit slower decays than antibody titers. These observations imply that next-generation COVID-19 vaccines should be designed to induce stronger cellular responses to sustain the generation of potent neutralizing antibodies.

Authors

Ricards Marcinkevics, Pamuditha N. Silva, Anna-Katharina Hankele, Charlyn Dörnte, Sarah Kadelka, Katharina Csik, Svenja Godbersen, Algera Goga, Lynn Hasenöhrl, Pascale Hirschi, Hasan Kabakci, Mary P. LaPierre, Johanna Mayrhofer, Alexandra C. Title, Xuan Shu, Nouell Baiioud, Sandra Bernal, Laura Dassisti, Mara D. Saenz-de-Juano, Meret Schmidhauser, Giulia Silvestrelli, Simon Z. Ulbrich, Thea J. Ulbrich, Tamara Wyss, Daniel J. Stekhoven, Faisal S. Al-Quaddoomi, Shuqing Yu, Mascha Binder, Christoph Schultheiβ, Claudia Zindel, Christoph Kolling, Jörg Goldhahn, Bahram Kasmapour Seighalani, Polina Zjablovskaja, Frank Hardung, Marc Schuster, Anne Richter, Yi-Ju Huang, Gereon Lauer, Herrad Baurmann, Jun Siong Low, Daniela Vaqueirinho, Sandra Jovic, Luca Piccoli, Sandra Ciesek, Julia E. Vogt, Federica Sallusto, Markus Stoffel, Susanne E. Ulbrich

Submitted

Frontiers in Immunology

Date

29.05.2023

LinkDOICode

Abstract

Spurious correlations are everywhere. While humans often do not perceive them, neural networks are notorious for learning unwanted associations, also known as biases, instead of the underlying decision rule. As a result, practitioners are often unaware of the biased decision-making of their classifiers. Such a biased model based on spurious correlations might not generalize to unobserved data, leading to unintended, adverse consequences. We propose Signal is Harder (SiH), a variational-autoencoder-based method that simultaneously trains a biased and unbiased classifier using a novel, disentangling reweighting scheme inspired by the focal loss. Using the unbiased classifier, SiH matches or improves upon the performance of state-of-the-art debiasing methods. To improve the interpretability of our technique, we propose a perturbation scheme in the latent space for visualizing the bias that helps practitioners become aware of the sources of spurious correlations.

Authors

Moritz Vandenhirtz, Laura Manduchi, Ricards Marcinkevics, Julia E. Vogt

Submitted

Domain Generalization Workshop, ICLR 2023

Date

04.05.2023

LinkCode

Abstract

Machine learning (ML) is a discipline emerging from computer science with close ties to statistics and applied mathematics. Its fundamental goal is the design of computer programs, or algorithms, that learn to perform a certain task in an automated manner. Without explicit rules or knowledge, ML algorithms observe and possibly, interact with the surrounding world by the use of available data. Typically, as a result of learning, algorithms distil observations of complex phenomena into a general model which summarises the patterns, or regularities, discovered from the data. Modern ML algorithms regularly break records achieving impressive performance at a wide range of tasks, e.g. game playing, protein structure prediction, searching for particles in high-energy physics, and forecasting precipitation. The utility of machine learning methods for healthcare is apparent: it is often argued that given vast amounts of heterogeneous data, our understanding of diseases, patient management and outcomes can be enriched with the insights from machine learning. In this chapter, we will provide a nontechnical introduction to the ML discipline aimed at a general audience with an affinity for biomedical applications. We will familiarise the reader with the common types of algorithms and typical tasks these algorithms can solve and illustrate these basic concepts by concrete examples of current machine learning applications in healthcare. We will conclude with a discussion of the open challenges, limitations, and potential impact of machine-learning-powered medicine.

Authors

Julia E. Vogt, Ece Özkan Elsen, Ricards Marcinkevics

Submitted

Chapter in Digital Medicine: Bringing Digital Solutions to Medical Practice

Date

31.03.2023

LinkDOI

Abstract

Background and Objectives: Remote patient monitoring (RPM) of vital signs and symptoms for lung transplant recipients (LTRs) has become increasingly relevant in many situations. Nevertheless, RPM research integrating multisensory home monitoring in LTRs is scarce. We developed a novel multisensory home monitoring device and tested it in the context of COVID-19 vaccinations. We hypothesize that multisensory RPM and smartphone-based questionnaire feedback on signs and symptoms will be well accepted among LTRs. To assess the usability and acceptability of a remote monitoring system consisting of wearable devices, including home spirometry and a smartphone-based questionnaire application for symptom and vital sign monitoring using wearable devices, during the first and second SARS-CoV-2 vaccination. Materials and Methods: Observational usability pilot study for six weeks of home monitoring with the COVIDA Desk for LTRs. During the first week after the vaccination, intensive monitoring was performed by recording data on physical activity, spirometry, temperature, pulse oximetry and self-reported symptoms, signs and additional measurements. During the subsequent days, the number of monitoring assessments was reduced. LTRs reported on their perceptions of the usability of the monitoring device through a purpose-designed questionnaire. Results: Ten LTRs planning to receive the first COVID-19 vaccinations were recruited. For the intensive monitoring study phase, LTRs recorded symptoms, signs and additional measurements. The most frequent adverse events reported were local pain, fatigue, sleep disturbance and headache. The duration of these symptoms was 5–8 days post-vaccination. Adherence to the main monitoring devices was high. LTRs rated usability as high. The majority were willing to continue monitoring. Conclusions: The COVIDA Desk showed favorable technical performance and was well accepted by the LTRs during the vaccination phase of the pandemic. The feasibility of the RPM system deployment was proven by the rapid recruitment uptake, technical performance (i.e., low number of errors), favorable user experience questionnaires and detailed individual user feedback.

Authors

Mace M. Schuurmans, Michal Muszynski, Xiang Li, Ricards Marcinkevics, Lukas Zimmerli, Diego Monserrat Lopez, Bruno Michel, Jonas Weiss, Rene Hage, Maurice Roeder, Julia E. Vogt, Thomas Brunschwiler

Submitted

Medicina

Date

20.03.2023

LinkDOI

Abstract

Interpretability and explainability are crucial for machine learning (ML) and statistical applications in medicine, economics, law, and natural sciences and form an essential principle for ML model design and development. Although interpretability and explainability have escaped a precise and universal definition, many models and techniques motivated by these properties have been developed over the last 30 years, with the focus currently shifting toward deep learning. We will consider concrete examples of state-of-the-art, including specially tailored rule-based, sparse, and additive classification models, interpretable representation learning, and methods for explaining black-box models post hoc. The discussion will emphasize the need for and relevance of interpretability and explainability, the divide between them, and the inductive biases behind the presented “zoo” of interpretable models and explanation methods.

Authors

Ricards Marcinkevics, Julia E. Vogt

Submitted

WIREs Data Mining and Knowledge Discovery

Date

28.02.2023

LinkDOI

Abstract

Many modern research fields increasingly rely on collecting and analysing massive, often unstructured, and unwieldy datasets. Consequently, there is growing interest in machine learning and artificial intelligence applications that can harness this `data deluge'. This broad nontechnical overview provides a gentle introduction to machine learning with a specific focus on medical and biological applications. We explain the common types of machine learning algorithms and typical tasks that can be solved, illustrating the basics with concrete examples from healthcare. Lastly, we provide an outlook on open challenges, limitations, and potential impacts of machine-learning-powered medicine.

Authors

Ricards Marcinkevics, Ece Özkan Elsen, Julia E. Vogt

Submitted

Arxiv

Date

23.12.2022

LinkDOI

Abstract

Deep neural networks for image-based screening and computer-aided diagnosis have achieved expert-level performance on various medical imaging modalities, including chest radiographs. Recently, several works have indicated that these state-of-the-art classifiers can be biased with respect to sensitive patient attributes, such as race or gender, leading to growing concerns about demographic disparities and discrimination resulting from algorithmic and model-based decision-making in healthcare. Fair machine learning has focused on mitigating such biases against disadvantaged or marginalised groups, mainly concentrating on tabular data or natural images. This work presents two novel intra-processing techniques based on fine-tuning and pruning an already-trained neural network. These methods are simple yet effective and can be readily applied post hoc in a setting where the protected attribute is unknown during the model development and test time. In addition, we compare several intra- and post-processing approaches applied to debiasing deep chest X-ray classifiers. To the best of our knowledge, this is one of the first efforts studying debiasing methods on chest radiographs. Our results suggest that the considered approaches successfully mitigate biases in fully connected and convolutional neural networks offering stable performance under various settings. The discussed methods can help achieve group fairness of deep medical image classifiers when deploying them in domains with different fairness considerations and constraints.

Authors

Ricards Marcinkevics, Ece Özkan Elsen, Julia E. Vogt

Submitted

The Seventh Machine Learning for Healthcare Conference, MLHC 2022

Date

05.08.2022

LinkCode

Abstract

Arguably, interpretability is one of the guiding principles behind the development of machine-learning-based healthcare decision support tools and computer-aided diagnosis systems. There has been a renewed interest in interpretable classification based on high-level concepts, including, among other model classes, the re-exploration of concept bottleneck models. By their nature, medical diagnosis, patient management, and monitoring require the assessment of multiple views and modalities to form a holistic representation of the patient's state. For instance, in ultrasound imaging, a region of interest might be registered from multiple views that are informative about different sets of clinically relevant features. Motivated by this, we extend the classical concept bottleneck model to the multiview classification setting by representation fusion across the views. We apply our multiview concept bottleneck model to the dataset of ultrasound images acquired from a cohort of pediatric patients with suspected appendicitis to predict the disease. The results suggest that auxiliary supervision from the concepts and aggregation across multiple views help develop more accurate and interpretable classifiers.

Authors

Ugne Klimiene, Ricards Marcinkevics, Patricia Reis Wolfertstetter, Ece Özkan Elsen, Alyssia Paschke, David Niederberger, Sven Wellmann, Christian Knorr, Julia E Vogt

Submitted

Oral spotlight at the 2nd Workshop on Interpretable Machine Learning in Healthcare (IMLH), ICML 2022

Date

23.07.2022

LinkCode

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces both B and T cell responses which jointly contribute to effective neutralization and clearance of the virus. Multiple compartments of circulating immune memory to SARS-CoV-2 are not fully understood. We analyzed humoral and T cell immune responses in young convalescent adults with previous asymptomatic SARS-CoV-2 infections or mildly symptomatic COVID-19 disease. We concomitantly measured antibodies in the blood and analyzed SARS-CoV-2-reactive T cell reaction in response to overlapping peptide pools of four viral proteins in peripheral blood mononuclear cells (PBMC). Using statistical and machine learning models, we investigated whether T cell reactivity predicted antibody status. Individuals with previous SARS-CoV-2 infection differed in T cell responses from non-infected individuals. Subjects with previous SARS-CoV-2 infection exhibited CD4+ T cell responses against S1-, N-proteins and CoV-Mix (containing N, M and S protein-derived peptides) that were dominant over CD8+ T cells. At the same time, signals against the M protein were less pronounced. Double positive IL2+/CD154+ and IFN+/TNF+ CD4+ T cells showed the strongest association with antibody titers. T-cell reactivity to CoV-Mix-, S1-, and N-antigens were most strongly associated with humoral immune response, specifically with a compound antibody titer consisting of RBD, S1, S2, and NP. The T cell phenotype of SARS-CoV-2 infected individuals was stable for four months, thereby exceeding antibody decay rates. Our findings demonstrate that mild COVID-19 infections can elicit robust SARS-CoV-2 T-cell reactive immunity against specific components of SARS-CoV-2.

Authors

Ricards Marcinkevics, Pamuditha Silva, Anna-Katharina Hankele, Katharina Csik, Svenja Godbersen, Algera Goga, Lynn Hasenöhrl, Pascale Hirschi, Hasan Kabakci, Mary P LaPierre, Johanna Mayrhofer, Alexandra Title, Xuan Shu, Nouell Baiioud, Sandra Bernal, Laura Dassisti, Mara D Saenz-de-Juano, Meret Schmidhauser, Giulia Silvestrelli, Simon Z Ulbrich, Thea J Ulbrich, Tamara Wyss, Daniel J Stekhoven, Faisal S Al-Quaddoomi, Shuqing Yu, Mascha Binder, Christoph Schultheiss, Claudia Zindel, Christoph Kolling, Jörg Goldhahn, Bahram Kasmapour, Polina Zjablovskaja, Frank Hardung, Anne Richter, Stefan Miltenyi, Luca Piccoli, Sandra Ciesek, Julia E Vogt, Federica Sallusto, Markus Stoffel, Susanne E Ulbrich

Submitted

The 1st Workshop on Healthcare AI and COVID-19 at ICML 2022

Date

22.07.2022

Abstract

Due to growing concerns about demographic disparities and discrimination resulting from algorithmic and model-based decision-making, recent research has focused on mitigating biases against already disadvantaged or marginalised groups in classification models. From the perspective of classification parity, the two commonest metrics for assessing fairness are statistical parity and equality of opportunity. Current approaches to debiasing in classification either require the knowledge of the protected attribute before or during training or are entirely agnostic to the model class and parameters. This work considers differentiable proxy functions for statistical parity and equality of opportunity and introduces two novel debiasing techniques for neural network classifiers based on fine-tuning and pruning an already-trained network. As opposed to the prior work leveraging adversarial training, the proposed methods are simple yet effective and can be readily applied post hoc. Our experimental results encouragingly suggest that these approaches successfully debias fully connected neural networks trained on tabular data and often outperform model-agnostic post-processing methods.

Authors

Ricards Marcinkevics, Ece Özkan Elsen, Julia E. Vogt

Submitted

Contributed talk at ICLR 2022 Workshop on Socially Responsible Machine Learning

Date

29.04.2022

LinkCode

Abstract

In this work, we study the problem of clustering survival data — a challenging and so far under-explored task. We introduce a novel semi-supervised probabilistic approach to cluster survival data by leveraging recent advances in stochastic gradient variational inference. In contrast to previous work, our proposed method employs a deep generative model to uncover the underlying distribution of both the explanatory variables and censored survival times. We compare our model to the related work on clustering and mixture models for survival data in comprehensive experiments on a wide range of synthetic, semi-synthetic, and real-world datasets, including medical imaging data. Our method performs better at identifying clusters and is competitive at predicting survival times. Relying on novel generative assumptions, the proposed model offers a holistic perspective on clustering survival data and holds a promise of discovering subpopulations whose survival is regulated by different generative mechanisms.

Authors

Laura Manduchi, Ricards Marcinkevics, Michela C. Massi, Thomas Weikert, Alexander Sauter, Verena Gotta, Timothy Müller, Flavio Vasella, Marian C. Neidert, Marc Pfister, Bram Stieltjes, Julia E. Vogt

Submitted

The Tenth International Conference on Learning Representations, ICLR 2022

Date

25.04.2022

LinkCode

Abstract

Appendicitis is a common childhood disease, the management of which still lacks consolidated international criteria. In clinical practice, heuristic scoring systems are often used to assess the urgency of patients with suspected appendicitis. Previous work on machine learning for appendicitis has focused on conventional classification models, such as logistic regression and tree-based ensembles. In this study, we investigate the use of risk supersparse linear integer models (risk SLIM) for learning data-driven risk scores to predict the diagnosis, management, and complications in pediatric patients with suspected appendicitis on a dataset consisting of 430 children from a tertiary care hospital. We demonstrate the efficacy of our approach and compare the performance of learnt risk scores to previous analyses with random forests. Risk SLIM is able to detect medically meaningful features and outperforms the traditional appendicitis scores, while at the same time is better suited for the clinical setting than tree-based ensembles.

Authors

Pedro Roig Aparicio, Ricards Marcinkevics, Patricia Reis Wolfertstetter, Sven Wellmann, Christian Knorr, Julia E. Vogt

Submitted

Short paper at 20th IEEE International Conference on Machine Learning and Applications, ICMLA 2021

Date

16.12.2021

LinkDOI

Abstract

Sleep is crucial to restore body functions and metabolism across nearly all tissues and cells, and sleep restriction is linked to various metabolic dysfunctions in humans. Using exhaled breath analysis by secondary electrospray ionization high-resolution mass spectrometry, we measured the human exhaled metabolome at 10-s resolution across a night of sleep in combination with conventional polysomnography. Our subsequent analysis of almost 2,000 metabolite features demonstrates rapid, reversible control of major metabolic pathways by the individual vigilance states. Within this framework, whereas a switch to wake reduces fatty acid oxidation, a switch to slow-wave sleep increases it, and the transition to rapid eye movement sleep results in elevation of tricarboxylic acid (TCA) cycle intermediates. Thus, in addition to daily regulation of metabolism, there exists a surprising and complex underlying orchestration across sleep and wake. Both likely play an important role in optimizing metabolic circuits for human performance and health.

Authors

Nora Nowak, Thomas Gaisl, Djordje Miladinovic, Ricards Marcinkevics, Martin Osswald, Stefan Bauer, Joachim Buhmann, Renato Zenobi, Pablo Sinues, Steven A. Brown, Malcolm Kohler

Submitted

Cell Reports

Date

26.10.2021

LinkDOICode

Abstract

Autonomic peripheral activity is partly governed by brain autonomic centers. However, there is still a lot of uncertainties regarding the precise link between peripheral and central autonomic biosignals. Clarifying these links could have a profound impact on the interpretability, and thus usefulness, of peripheral autonomic biosignals captured with wearable devices. In this study, we take advantage of a unique dataset consisting of intracranial stereo-electroencephalography (SEEG) and peripheral biosignals acquired simultaneously for several days from four subjects undergoing epilepsy monitoring. Compared to previous work, we apply a deep neural network to explore high-dimensional nonlinear correlations between the cerebral brainwaves and variations in heart rate and electrodermal activity (EDA). Further, neural network explainability methods were applied to identify most relevant brainwave frequencies, brain regions and temporal information to predict a specific biosignal. Strongest brain-peripheral correlations were observed from contacts located in the central autonomic network, in particular in the alpha, theta and 52 to 58 Hz frequency band. Furthermore, a temporal delay of 12 to 14 s between SEEG and EDA signal was observed. Finally, we believe that this pilot study demonstrates a promising approach to mapping brain-peripheral relationships in a data-driven manner by leveraging the expressiveness of deep neural networks.

Authors

Alexander H. Hatteland, Ricards Marcinkevics, Renaud Marquis, Thomas Frick, Ilona Hubbard, Julia E. Vogt, Thomas Brunschwiler, Philippe Ryvlin

Submitted

Best paper award at IEEE International Conference on Digital Health, ICDH 2021

Date

05.09.2021

LinkDOI

Abstract

Background: Given the absence of consolidated and standardized international guidelines for managing pediatric appendicitis and the few strictly data-driven studies in this specific, we investigated the use of machine learning (ML) classifiers for predicting the diagnosis, management and severity of appendicitis in children. Materials and Methods: Predictive models were developed and validated on a dataset acquired from 430 children and adolescents aged 0-18 years, based on a range of information encompassing history, clinical examination, laboratory parameters, and abdominal ultrasonography. Logistic regression, random forests, and gradient boosting machines were used for predicting the three target variables. Results: A random forest classifier achieved areas under the precision-recall curve of 0.94, 0.92, and 0.70, respectively, for the diagnosis, management, and severity of appendicitis. We identified smaller subsets of 6, 17, and 18 predictors for each of targets that sufficed to achieve the same performance as the model based on the full set of 38 variables. We used these findings to develop the user-friendly online Appendicitis Prediction Tool for children with suspected appendicitis. Discussion: This pilot study considered the most extensive set of predictor and target variables to date and is the first to simultaneously predict all three targets in children: diagnosis, management, and severity. Moreover, this study presents the first ML model for appendicitis that was deployed as an open access easy-to-use online tool. Conclusion: ML algorithms help to overcome the diagnostic and management challenges posed by appendicitis in children and pave the way toward a more personalized approach to medical decision-making. Further validation studies are needed to develop a finished clinical decision support system.

Authors

Ricards Marcinkevics, Patricia Reis Wolfertstetter, Sven Wellmann, Christian Knorr, Julia E Vogt

Submitted

Frontiers in Pediatrics

Date

29.04.2021

LinkDOICode

Abstract

Survival analysis has gained significant attention in the medical domain with many far-reaching applications. Although a variety of machine learning methods have been introduced for tackling time-to-event prediction in unstructured data with complex dependencies, clustering of survival data remains an under-explored problem. The latter is particularly helpful in discovering patient subpopulations whose survival is regulated by different generative mechanisms, a critical problem in precision medicine. To this end, we introduce a novel probabilistic approach to cluster survival data in a variational deep clustering setting. Our proposed method employs a deep generative model to uncover the underlying distribution of both the explanatory variables and the potentially censored survival times. We compare our model to the related work on survival clustering in comprehensive experiments on a range of synthetic, semi-synthetic, and real-world datasets. Our proposed method performs better at identifying clusters and is competitive at predicting survival times in terms of the concordance index and relative absolute error.

Authors

Laura Manduchi, Ricards Marcinkevics, Julia E. Vogt

Submitted

Contributed talk at AI for Public Health Workshop at ICLR 2021

Date

09.04.2021

Link

Abstract

Exploratory analysis of time series data can yield a better understanding of complex dynamical systems. Granger causality is a practical framework for analysing interactions in sequential data, applied in a wide range of domains. In this paper, we propose a novel framework for inferring multivariate Granger causality under nonlinear dynamics based on an extension of self-explaining neural networks. This framework is more interpretable than other neural-network-based techniques for inferring Granger causality, since in addition to relational inference, it also allows detecting signs of Granger-causal effects and inspecting their variability over time. In comprehensive experiments on simulated data, we show that our framework performs on par with several powerful baseline methods at inferring Granger causality and that it achieves better performance at inferring interaction signs. The results suggest that our framework is a viable and more interpretable alternative to sparse-input neural networks for inferring Granger causality.

Authors

Ricards Marcinkevics, Julia E. Vogt

Submitted

Ninth International Conference on Learning Representations, ICLR 2021

Date

15.01.2021

LinkCode

Abstract

In this review, we examine the problem of designing interpretable and explainable machine learning models. Interpretability and explainability lie at the core of many machine learning and statistical applications in medicine, economics, law, and natural sciences. Although interpretability and explainability have escaped a clear universal definition, many techniques motivated by these properties have been developed over the recent 30 years with the focus currently shifting towards deep learning methods. In this review, we emphasise the divide between interpretability and explainability and illustrate these two different research directions with concrete examples of the state-of-the-art. The review is intended for a general machine learning audience with interest in exploring the problems of interpretation and explanation beyond logistic regression or random forest variable importance. This work is not an exhaustive literature survey, but rather a primer focusing selectively on certain lines of research which the authors found interesting or informative.

Authors

Ricards Marcinkevics, Julia E. Vogt

Submitted

Arxiv

Date

04.12.2020

Link

Abstract

Exploratory analysis of time series data can yield a better understanding of complex dynamical systems. Granger causality is a practical framework for analysing interactions in sequential data, applied in a wide range of domains. In this paper, we propose a novel framework for inferring multivariate Granger causality under nonlinear dynamics based on an extension of self-explaining neural networks. This framework is more interpretable than other neural-network-based techniques for inferring Granger causality, since in addition to relational inference, it also allows detecting signs of Granger-causal effects and inspecting their variability over time. In comprehensive experiments on simulated data, we show that our framework performs on par with several powerful baseline methods at inferring Granger causality and that it achieves better performance at inferring interaction signs. The results suggest that our framework is a viable and more interpretable alternative to sparse-input neural networks for inferring Granger causality.

Authors

Ricards Marcinkevics, Julia E. Vogt

Submitted

Interpretable Inductive Biases and Physically Structured Learning Workshop, NeurIPS 2020

Date

01.11.2020

Link

Abstract

Multimodal generative models learn a joint distribution over multiple modalities and thus have the potential to learn richer representations than unimodal models. However, current approaches are either inefficient in dealing with more than two modalities or fail to capture both modality-specific and shared variations. We introduce a new multimodal generative model that integrates both modality-specific and shared factors and aggregates shared information across any subset of modalities efficiently. Our method partitions the latent space into disjoint subspaces for modality-specific and shared factors and learns to disentangle these in a purely self-supervised manner. In extensive experiments, we show improvements in representation learning and generative performance compared to previous methods and showcase the disentanglement capabilities.

Authors

Imant Daunhawer, Thomas M. Sutter, Ricards Marcinkevics, Julia E. Vogt

Submitted

GCPR 2020

Date

10.09.2020

Link

Abstract

The classification of time series data is a well-studied problem with numerous practical applications, such as medical diagnosis and speech recognition. A popular and effective approach is to classify new time series in the same way as their nearest neighbours, whereby proximity is defined using Dynamic Time Warping (DTW) distance, a measure analogous to sequence alignment in bioinformatics. However, practitioners are not only interested in accurate classification, they are also interested in why a time series is classified a certain way. To this end, we introduce here the problem of finding a minimum length subsequence of a time series, the removal of which changes the outcome of the classification under the nearest neighbour algorithm with DTW distance. Informally, such a subsequence is expected to be relevant for the classification and can be helpful for practitioners in interpreting the outcome. We describe a simple but optimized implementation for detecting these subsequences and define an accompanying measure to quantify the relevance of every time point in the time series for the classification. In tests on electrocardiogram data we show that the algorithm allows discovery of important subsequences and can be helpful in detecting abnormalities in cardiac rhythms distinguishing sick from healthy patients.

Authors

Ricards Marcinkevics, Steven Kelk, Carlo Galuzzi, Berthold Stegemann

Submitted

Arxiv

Date

26.01.2019

Link

Abstract

Aims: The identification of arrhythmogenic right ventricular dysplasia (ARVD) from 12-channel standard electrocardiogram (ECG) is challenging. High density ECG data may identify lead locations and criteria with a higher sensitivity. Methods and results: Eighty-channel ECG recording from patients diagnosed with ARVD and controls were quantified by magnitude and integral measures of QRS and T waves and by a measure (the average silhouette width) of differences in the shapes of the normalized ECG cycles. The channels with the best separability between ARVD patients and controls were near the right ventricular wall, at the third intercostal space. These channels showed pronounced differences in P waves compared to controls as well as the expected differences in QRS and T waves. Conclusion: Multichannel recordings, as in body surface mapping, add little to the reliability of diagnosing ARVD from ECGs. However, repositioning ECG electrodes to a high anterior position can improve the identification of ECG variations in ARVD. Additionally, increased P wave amplitude appears to be associated with ARVD.

Authors

Ricards Marcinkevics, James O’Neill, Hannah Law, Eleftheria Pervolaraki, Andrew Hogarth, Craig Russell, Berthold Stegemann, Arun V Holden, Muzahir H Tayebjee

Submitted

EP Europace

Date

29.08.2017

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