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The success of immuno-oncology treatments promises long-term cancer remission for an increasing number of patients. The response to checkpoint inhibitor drugs has shown a correlation with the presence of immune cells in the tumor and tumor microenvironment. An in-depth understanding of the spatial localization of immune cells is therefore critical for understanding the tumor’s immune landscape and predicting drug response. Computer-aided systems are well suited for efficiently quantifying immune cells in their spatial context. Conventional image analysis approaches are often based on color features and therefore require a high level of manual interaction. More robust image analysis methods based on deep learning are expected to decrease this reliance on human interaction and improve the reproducibility of immune cell scoring. However, these methods require sufficient training data and previous work has reported low robustness of these algorithms when they are tested on out-of-distribution data from different pathology labs or samples from different organs. In this work, we used a new image analysis pipeline to explicitly evaluate the robustness of marker-labeled lymphocyte quantification algorithms depending on the number of training samples before and after being transferred to a new tumor indication. For these experiments, we adapted the RetinaNet architecture for the task of T-lymphocyte detection and employed transfer learning to bridge the domain gap between tumor indications and reduce the annotation costs for unseen domains. On our test set, we achieved human-level performance for almost all tumor indications with an average precision of 0.74 in-domain and 0.72–0.74 cross-domain. From our results, we derive recommendations for model development regarding annotation extent, training sample selection, and label extraction for the development of robust algorithms for immune cell scoring. By extending the task of marker-labeled lymphocyte quantification to a multi-class detection task, the pre-requisite for subsequent analyses, e.g., distinguishing lymphocytes in the tumor stroma from tumor-infiltrating lymphocytes, is met.
Systems are becoming increasingly more adaptive, using techniques like machine learning to enhance their behavior on their own rather than only through human developers programming them. We analyze the impact the advent of these new techniques has on the discipline of rigorous software engineering, especially on the issue of quality assurance. To this end, we provide a general description of the processes related to machine learning and embed them into a formal framework for the analysis of adaptivity, recognizing that to test an adaptive system a new approach to adaptive testing is necessary. We introduce scenario coevolution as a design pattern describing how system and test can work as antagonists in the process of software evolution. While the general pattern applies to large-scale processes (including human developers further augmenting the system), we show all techniques on a smaller-scale example of an agent navigating a simple smart factory. We point out new aspects in software engineering for adaptive systems that may be tackled naturally using scenario coevolution. This work is a substantially extended take on Gabor et al. (International symposium on leveraging applications of formal methods, Springer, pp 137–154, 2018).
In cooperative game theory bargaining games refer to situations where players can agree to any one of a variety of outcomes but there is a conflict on which specific outcome to choose. However, the players cannot impose a specific outcome on others and if no agreement is reached all players receive a predetermined status quo outcome. Bargaining games have been studied from a variety of fields, including game theory, economics, psychology and simulation based methods like genetic algorithms. In this work we extend the analysis by means of deep multi-agent reinforcement learning (MARL). To study the dynamics of bargaining with reinforcement learning we propose two different bargaining environments which display the following situations: in the first domain two agents have to agree on the division of an asset, e.g., the division of a fixed amount of money between each other. The second domain models a seller-buyer scenario in which agents must agree on a price for a product. We empirica lly demonstrate that the bargaining result under MARL is influenced by agents’ risk-aversion as well as information asymmetry between agents.
Robustness to out-of-distribution (OOD) data is an important goal in building reliable machine learning systems. As a first step towards a solution, we consider the problem of detecting such data in a value-based deep reinforcement learning (RL) setting. Modelling this problem as a one-class classification problem, we propose a framework for uncertainty-based OOD classification: UBOOD. It is based on the effect that an agent’s epistemic uncertainty is reduced for situations encountered during training (in-distribution), and thus lower than for unencountered (OOD) situations. Being agnostic towards the approach used for estimating epistemic uncertainty, combinations with different uncertainty estimation methods, e.g. approximate Bayesian inference methods or ensembling techniques are possible. Evaluation shows that the framework produces reliable classification results when combined with ensemble-based estimators, while the combination with concrete dropout-based estimators fails to r eliably detect OOD situations.
Inheritance-based diversity measures for explicit convergence control in evolutionary algorithms
(2018)
Preparing for the unexpected
(2018)