Maria Kalweit

Marieke Wesselkamp, Matthew Chantry, Ewan Pinnington et al.

Most useful weather prediction for the public is near the surface. The processes that are most relevant for near-surface weather prediction are also those that are most interactive and exhibit positive feedback or have key role in energy partitioning. Land surface models (LSMs) consider these processes together with surface heterogeneity and forecast water, carbon and energy fluxes, and coupled with an atmospheric model provide boundary and initial conditions. This numerical parametrization of atmospheric boundaries being computationally expensive, statistical surrogate models are increasingly used to accelerated progress in experimental research. We evaluated the efficiency of three surrogate models in speeding up experimental research by simulating land surface processes, which are integral to forecasting water, carbon, and energy fluxes in coupled atmospheric models. Specifically, we compared the performance of a Long-Short Term Memory (LSTM) encoder-decoder network, extreme gradient boosting, and a feed-forward neural network within a physics-informed multi-objective framework. This framework emulates key states of the ECMWF's Integrated Forecasting System (IFS) land surface scheme, ECLand, across continental and global scales. Our findings indicate that while all models on average demonstrate high accuracy over the forecast period, the LSTM network excels in continental long-range predictions when carefully tuned, the XGB scores consistently high across tasks and the MLP provides an excellent implementation-time-accuracy trade-off. The runtime reduction achieved by the emulators in comparison to the full numerical models are significant, offering a faster, yet reliable alternative for conducting numerical experiments on land surfaces.

Hao Zhu, Brice De La Crompe, Gabriel Kalweit et al.

In advancing the understanding of natural decision-making processes, inverse reinforcement learning (IRL) methods have proven instrumental in reconstructing animal's intentions underlying complex behaviors. Given the recent development of a continuous-time multi-intention IRL framework, there has been persistent inquiry into inferring discrete time-varying rewards with IRL. To address this challenge, we introduce the class of hierarchical inverse Q-learning (HIQL) algorithms. Through an unsupervised learning process, HIQL divides expert trajectories into multiple intention segments, and solves the IRL problem independently for each. Applying HIQL to simulated experiments and several real animal behavior datasets, our approach outperforms current benchmarks in behavior prediction and produces interpretable reward functions. Our results suggest that the intention transition dynamics underlying complex decision-making behavior is better modeled by a step function instead of a smoothly varying function. This advancement holds promise for neuroscience and cognitive science, contributing to a deeper understanding of decision-making and uncovering underlying brain mechanisms.

Mehdi Naouar, Gabriel Kalweit, Ignacio Mastroleo et al.

Cancer detection and classification from gigapixel whole slide images of stained tissue specimens has recently experienced enormous progress in computational histopathology. The limitation of available pixel-wise annotated scans shifted the focus from tumor localization to global slide-level classification on the basis of (weakly-supervised) multiple-instance learning despite the clinical importance of local cancer detection. However, the worse performance of these techniques in comparison to fully supervised methods has limited their usage until now for diagnostic interventions in domains of life-threatening diseases such as cancer. In this work, we put the focus back on tumor localization in form of a patch-level classification task and take up the setting of so-called coarse annotations, which provide greater training supervision while remaining feasible from a clinical standpoint. To this end, we present a novel ensemble method that not only significantly improves the detection accuracy of metastasis on the open CAMELYON16 data set of sentinel lymph nodes of breast cancer patients, but also considerably increases its robustness against noise while training on coarse annotations. Our experiments show that better results can be achieved with our technique making it clinically feasible to use for cancer diagnosis and opening a new avenue for translational and clinical research.

Yannick Vogt, Mehdi Naouar, Maria Kalweit et al.

Antibodies offer great potential for the treatment of various diseases. However, the discovery of therapeutic antibodies through traditional wet lab methods is expensive and time-consuming. The use of generative models in designing antibodies therefore holds great promise, as it can reduce the time and resources required. Recently, the class of diffusion models has gained considerable traction for their ability to synthesize diverse and high-quality samples. In their basic form, however, they lack mechanisms to optimize for specific properties, such as binding affinity to an antigen. In contrast, the class of offline Reinforcement Learning (RL) methods has demonstrated strong performance in navigating large search spaces, including scenarios where frequent real-world interaction, such as interaction with a wet lab, is impractical. Our novel method, BetterBodies, which combines Variational Autoencoders (VAEs) with RL guided latent diffusion, is able to generate novel sets of antibody CDRH3 sequences from different data distributions. Using the Absolut! simulator, we demonstrate the improved affinity of our novel sequences to the SARS-CoV spike receptor-binding domain. Furthermore, we reflect biophysical properties in the VAE latent space using a contrastive loss and add a novel Q-function based filtering to enhance the affinity of generated sequences. In conclusion, methods such as ours have the potential to have great implications for real-world biological sequence design, where the generation of novel high-affinity binders is a cost-intensive endeavor.

Yannick Vogt, Mehdi Naouar, Maria Kalweit et al.

The field of antibody-based therapeutics has grown significantly in recent years, with targeted antibodies emerging as a potentially effective approach to personalized therapies. Such therapies could be particularly beneficial for complex, highly individual diseases such as cancer. However, progress in this field is often constrained by the extensive search space of amino acid sequences that form the foundation of antibody design. In this study, we introduce a novel reinforcement learning method specifically tailored to address the unique challenges of this domain. We demonstrate that our method can learn the design of high-affinity antibodies against multiple targets in silico, utilizing either online interaction or offline datasets. To the best of our knowledge, our approach is the first of its kind and outperforms existing methods on all tested antigens in the Absolut! database.

Iman Nematollahi, Jose Francisco Villena-Ossa, Alina Moter et al.

Machine learning models of cellular interaction dynamics hold promise for understanding cell behavior. Natural killer (NK) cell cytotoxicity is a prominent example of such interaction dynamics and is commonly studied using time-resolved multi-channel fluorescence microscopy. Although tumor cell death events can be annotated at single frames, NK cytotoxic outcome emerges over time from cellular interactions and cannot be reliably inferred from frame-wise classification alone. We introduce BLINK, a trajectory-based recurrent state-space model that serves as a cell world model for NK-tumor interactions. BLINK learns latent interaction dynamics from partially observed NK-tumor interaction sequences and predicts apoptosis increments that accumulate into cytotoxic outcomes. Experiments on long-term time-lapse NK-tumor recordings show improved cytotoxic outcome detection and enable forecasting of future outcomes, together with an interpretable latent representation that organizes NK trajectories into coherent behavioral modes and temporally structured interaction phases. BLINK provides a unified framework for quantitative evaluation and structured modeling of NK cytotoxic behavior at the single-cell level.

Julia Hindel, Ema Mekic, Enamundram Naga Karthik et al.

Robot-assisted surgeries rely on accurate and real-time scene understanding to safely guide surgical instruments. However, segmentation models trained on static datasets face key limitations when deployed in these dynamic and evolving surgical environments. Class-incremental semantic segmentation (CISS) allows models to continually adapt to new classes while avoiding catastrophic forgetting of prior knowledge, without training on previous data. In this work, we build upon the recently introduced Taxonomy-Oriented Poincaré-regularized Incremental Class Segmentation (TOPICS) approach and propose an enhanced variant, termed TOPICS+, specifically tailored for robust segmentation of surgical scenes. Concretely, we incorporate the Dice loss into the hierarchical loss formulation to handle strong class imbalances, introduce hierarchical pseudo-labeling, and design tailored label taxonomies for robotic surgery environments. We also propose six novel CISS benchmarks designed for robotic surgery environments including multiple incremental steps and several semantic categories to emulate realistic class-incremental settings in surgical environments. In addition, we introduce a refined set of labels with more than 144 classes on the Syn-Mediverse synthetic dataset, hosted online as an evaluation benchmark. We make the code and trained models publicly available at http://topics.cs.uni-freiburg.de.

Maria Kalweit, Gabriel Kalweit, Moritz Werling et al.

Challenging problems of deep reinforcement learning systems with regard to the application on real systems are their adaptivity to changing environments and their efficiency w.r.t. computational resources and data. In the application of learning lane-change behavior for autonomous driving, agents have to deal with a varying number of surrounding vehicles. Furthermore, the number of required transitions imposes a bottleneck, since test drivers cannot perform an arbitrary amount of lane changes in the real world. In the off-policy setting, additional information on solving the task can be gained by observing actions from others. While in the classical RL setup this knowledge remains unused, we use other drivers as surrogates to learn the agent's value function more efficiently. We propose Surrogate Q-learning that deals with the aforementioned problems and reduces the required driving time drastically. We further propose an efficient implementation based on a permutation-equivariant deep neural network architecture of the Q-function to estimate action-values for a variable number of vehicles in sensor range. We show that the architecture leads to a novel replay sampling technique we call Scene-centric Experience Replay and evaluate the performance of Surrogate Q-learning and Scene-centric Experience Replay in the open traffic simulator SUMO. Additionally, we show that our methods enhance real-world applicability of RL systems by learning policies on the real highD dataset.