Welcome to the Biomedical Informatics Lab of Prof. Dr. Gunnar Rätsch

The research in our group lies at the interface between methods research in Machine Learning, Genomics and Medical Informatics and relevant applications in biology and medicine.

We develop new analysis techniques that are capable of dealing with large amounts of medical and genomic data. These techniques aim to provide accurate predictions on the phenomenon at hand and to comprehensibly provide reasons for their prognoses, and thereby assist in gaining new biomedical insights.

Current research includes a) Machine Learning related to time-series analysis and iterative optimization algorithms, b) methods for transcriptome analyses to study transcriptome alterations in cancer, c) developing clinical decision support systems, in particular, for time series data from intensive care units, d) new graph genome algorithms to store and analyze very large sets of genomic sequences, and e) developing methods and resources for international sharing of genomic and clinical data, for instance, about variants in BRCA1/2.

Abstract The recent success of machine learning methods applied to time series collected from Intensive Care Units (ICU) exposes the lack of standardized machine learning benchmarks for developing and comparing such methods. While raw datasets, such as MIMIC-IV or eICU, can be freely accessed on Physionet, the choice of tasks and pre-processing is often chosen ad-hoc for each publication, limiting comparability across publications. In this work, we aim to improve this situation by providing a benchmark covering a large spectrum of ICU-related tasks. Using the HiRID dataset, we define multiple clinically relevant tasks in collaboration with clinicians. In addition, we provide a reproducible end-to-end pipeline to construct both data and labels. Finally, we provide an in-depth analysis of current state-of-the-art sequence modeling methods, highlighting some limitations of deep learning approaches for this type of data. With this benchmark, we hope to give the research community the possibility of a fair comparison of their work.

Authors Hugo Yèche, Rita Kuznetsova, Marc Zimmermann, Matthias Hüser, Xinrui Lyu, Martin Faltys, Gunnar Rätsch

Submitted NeurIPS 2021 (Datasets and Benchmarks)

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Abstract Clustering high-dimensional data, such as images or biological measurements, is a long-standing problem and has been studied extensively. Recently, Deep Clustering gained popularity due to its flexibility in fitting the specific peculiarities of complex data. Here we introduce the Mixture-of-Experts Similarity Variational Autoencoder (MoE-Sim-VAE), a novel generative clustering model. The model can learn multi-modal distributions of high-dimensional data and use these to generate realistic data with high efficacy and efficiency. MoE-Sim-VAE is based on a Variational Autoencoder (VAE), where the decoder consists of a Mixture-of-Experts (MoE) architecture. This specific architecture allows for various modes of the data to be automatically learned by means of the experts. Additionally, we encourage the lower dimensional latent representation of our model to follow a Gaussian mixture distribution and to accurately represent the similarities between the data points. We assess the performance of our model on the MNIST benchmark data set and a challenging real-world task of defining cell subpopulations from mass cytometry (CyTOF) measurements on hundreds of different datasets. MoE-Sim-VAE exhibits superior clustering performance on all these tasks in comparison to the baselines as well as competitor methods and we show that the MoE architecture in the decoder reduces the computational cost of sampling specific data modes with high fidelity.

Authors Andreas Kopf, Vincent Fortuin, Vignesh Ram Somnath, Manfred Claassen

Submitted PLOS Computational Biology

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Abstract Intensive care units (ICU) are increasingly looking towards machine learning for methods to provide online monitoring of critically ill patients. In machine learning, online monitoring is often formulated as a supervised learning problem. Recently, contrastive learning approaches have demonstrated promising improvements over competitive supervised benchmarks. These methods rely on well-understood data augmentation techniques developed for image data which do not apply to online monitoring. In this work, we overcome this limitation by supplementing time-series data augmentation techniques with a novel contrastive learning objective which we call neighborhood contrastive learning (NCL). Our objective explicitly groups together contiguous time segments from each patient while maintaining state-specific information. Our experiments demonstrate a marked improvement over existing work applying contrastive methods to medical time-series.

Authors Hugo Yèche, Gideon Dresdner, Francesco Locatello, Matthias Hüser, Gunnar Rätsch

Submitted ICML 2021

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Abstract With a mortality rate of 5.4 million lives worldwide every year and a healthcare cost of more than 16 billion dollars in the USA alone, sepsis is one of the leading causes of hospital mortality and an increasing concern in the ageing western world. Recently, medical and technological advances have helped re-define the illness criteria of this disease, which is otherwise poorly understood by the medical society. Together with the rise of widely accessible Electronic Health Records, the advances in data mining and complex nonlinear algorithms are a promising avenue for the early detection of sepsis. This work contributes to the research effort in the field of automated sepsis detection with an open-access labelling of the medical MIMIC-III data set. Moreover, we propose MGP-AttTCN: a joint multitask Gaussian Process and attention-based deep learning model to early predict the occurrence of sepsis in an interpretable manner. We show that our model outperforms the current state-of-the-art and present evidence that different labelling heuristics lead to discrepancies in task difficulty.

Authors Margherita Rosnati, Vincent Fortuin

Submitted PLOS One

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Abstract Generating interpretable visualizations of multivariate time series in the intensive care unit is of great practical importance. Clinicians seek to condense complex clinical observations into intuitively understandable critical illness patterns, like failures of different organ systems. They would greatly benefit from a low-dimensional representation in which the trajectories of the patients' pathology become apparent and relevant health features are highlighted. To this end, we propose to use the latent topological structure of Self-Organizing Maps (SOMs) to achieve an interpretable latent representation of ICU time series and combine it with recent advances in deep clustering. Specifically, we (a) present a novel way to fit SOMs with probabilistic cluster assignments (PSOM), (b) propose a new deep architecture for probabilistic clustering (DPSOM) using a VAE, and (c) extend our architecture to cluster and forecast clinical states in time series (T-DPSOM). We show that our model achieves superior clustering performance compared to state-of-the-art SOM-based clustering methods while maintaining the favorable visualization properties of SOMs. On the eICU data-set, we demonstrate that T-DPSOM provides interpretable visualizations of patient state trajectories and uncertainty estimation. We show that our method rediscovers well-known clinical patient characteristics, such as a dynamic variant of the Acute Physiology And Chronic Health Evaluation (APACHE) score. Moreover, we illustrate how it can disentangle individual organ dysfunctions on disjoint regions of the two-dimensional SOM map.

Authors Laura Manduchi, Matthias Hüser, Martin Faltys, Julia Vogt, Gunnar Rätsch, Vincent Fortuin

Submitted ACM-CHIL 2021

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