The BMI lab bridges research in Machine Learning and Sequence Analysis methodology research and its application to biomedical problems. We collaborate with biologists and clinicians to develop real-world solutions.
We work on research questions and foundational challenges in storing, analysing, and searching extensive heterogeneous and temporal data, especially in the biomedical domain. Our lab members address technical and non-technical research questions in collaboration with biologists and clinicians. At the research group’s core is an active knowledge exchange in both directions between the methods and the application-driven researchers.
The emergence of data-driven medicine leverages data and algorithms to shape how we diagnose and treat patients. Machine Learning approaches allow us to capitalise on the vast amount of data produced in clinical settings to generate novel biomedical insights and build more precise predictive models of disease outcomes and treatment efficacy.
We work towards this transformation mainly but not exclusively in two key areas. One key application area is the analysis of heterogeneous data of cancer patients. For Genomics, we develop algorithms for storing, compressing, and searching extensive genomics datasets. Another key area is the development of time series models of patient health states and early warning systems for intensive care units.
Abstract Understanding and predicting molecular responses towards external perturbations is a core question in molecular biology. Technological advancements in the recent past have enabled the generation of high-resolution single-cell data, making it possible to profile individual cells under different experimentally controlled perturbations. However, cells are typically destroyed during measurement, resulting in unpaired distributions over either perturbed or non-perturbed cells. Leveraging the theory of optimal transport and the recent advents of convex neural architectures, we learn a coupling describing the response of cell populations upon perturbation, enabling us to predict state trajectories on a single-cell level. We apply our approach, CellOT, to predict treatment responses of 21,650 cells subject to four different drug perturbations. CellOT outperforms current state-of-the-art methods both qualitatively and quantitatively, accurately capturing cellular behavior shifts across all different drugs.
Authors Charlotte Bunne, Stefan Stark, Gabriele Gut, Jacobo Sarabia del Castillo, Mitchell Levesque, Kjong Van Lehmann, Lucas Pelkmans, Andreas Krause, Gunnar Rätsch
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)
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
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
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