Representing and quantifying Minimal Residual Disease (MRD) in Acute Myeloid Leukemia (AML), a type of cancer that affects the blood and bone marrow, is essential in the prognosis and follow-up of AML patients. As traditional cytological analysis cannot detect leukemia cells below 5\%, the analysis of flow cytometry dataset is expected to provide more reliable results. In this paper, we explore statistical learning methods based on optimal transport (OT) to achieve a relevant low-dimensional representation of multi-patient flow cytometry measurements (FCM) datasets considered as high-dimensional probability distributions. Using the framework of OT, we justify the use of the K-means algorithm for dimensionality reduction of multiple large-scale point clouds through mean measure quantization by merging all the data into a single point cloud. After this quantization step, the visualization of the intra and inter-patients FCM variability is carried out by embedding low-dimensional quantized probability measures into a linear space using either Wasserstein Principal Component Analysis (PCA) through linearized OT or log-ratio PCA of compositional data. Using a publicly available FCM dataset and a FCM dataset from Bordeaux University Hospital, we demonstrate the benefits of our approach over the popular kernel mean embedding technique for statistical learning from multiple high-dimensional probability distributions. We also highlight the usefulness of our methodology for low-dimensional projection and clustering patient measurements according to their level of MRD in AML from FCM. In particular, our OT-based approach allows a relevant and informative two-dimensional representation of the results of the FlowSom algorithm, a state-of-the-art method for the detection of MRD in AML using multi-patient FCM.

This paper presents FlowCyt, the first comprehensive benchmark for multi-class single-cell classification in flow cytometry data. The dataset comprises bone marrow samples from 30 patients, with each cell characterized by twelve markers. Ground truth labels identify five hematological cell types: T lymphocytes, B lymphocytes, Monocytes, Mast cells, and Hematopoietic Stem/Progenitor Cells (HSPCs). Experiments utilize supervised inductive learning and semi-supervised transductive learning on up to 1 million cells per patient. Baseline methods include Gaussian Mixture Models, XGBoost, Random Forests, Deep Neural Networks, and Graph Neural Networks (GNNs). GNNs demonstrate superior performance by exploiting spatial relationships in graph-encoded data. The benchmark allows standardized evaluation of clinically relevant classification tasks, along with exploratory analyses to gain insights into hematological cell phenotypes. This represents the first public flow cytometry benchmark with a richly annotated, heterogeneous dataset. It will empower the development and rigorous assessment of novel methodologies for single-cell analysis.

Flow cytometry mainly used for detecting the characteristics of a number of biochemical substances based on the expression of specific markers in cells. It is particularly useful for detecting membrane surface receptors, antigens, ions, or during DNA/RNA expression. Not only can it be employed as a biomedical research tool for recognising distinctive types of cells in mixed populations, but it can also be used as a diagnostic tool for classifying abnormal cell populations connected with disease. Modern flow cytometers can rapidly analyse tens of thousands of cells at the same time while also measuring multiple parameters from a single cell. However, the rapid development of flow cytometers makes it challenging for conventional analysis methods to interpret flow cytometry data. Researchers need to be able to distinguish interesting-looking cell populations manually in multi-dimensional data collected from millions of cells. Thus, it is essential to find a robust approach for analysing flow cytometry data automatically, specifically in identifying cell populations automatically. This thesis mainly concerns discover the potential shortcoming of current automated-gating algorithms in both real datasets and synthetic datasets. Three representative automated clustering algorithms are selected to be applied, compared and evaluated by completely and partially automated gating. A subspace clustering ProClus also implemented in this thesis. The performance of ProClus in flow cytometry is not well, but it is still a useful algorithm to detect noise.

The presence of cancer of the lymphatic system is often determined by analyzing samples from the blood or bone marrow. A team led by Prof. Dr. Peter Krawitz from the University of Bonn had already shown in 2020 that artificial intelligence can help with the diagnosis of such lymphomas and leukemias. The technology fully utilizes the potential of all measurement values and increases the speed as well as the objectivity of the analyses compared to established processes. The method has now been further developed so that even smaller laboratories can benefit from this freely accessible machine learning method - an important step towards clinical practice. The study has now been published in the journal Patterns.

Lymph nodes become swollen, there is weight loss and fatigue, as well as fevers and infections - these are typical symptoms of malignant B-cell lymphomas and related leukemias. If such a cancer of the lymphatic system is suspected, the physician takes a blood or bone marrow sample and sends it to specialized laboratories. This is where flow cytometry comes in. Flow cytometry is a method in which the blood cells flow past measurement sensors at high speed. The properties of the cells can be detected depending on their shape, structure or coloring.

The presence of cancer of the lymphatic system is often determined by analyzing samples from the blood or bone marrow. A team led by Prof. Dr. Peter Krawitz from the University of Bonn had already shown in 2020 that artificial intelligence can help with the diagnosis of such lymphomas and leukemias. The technology fully utilizes the potential of all measurement values and increases the speed as well as the objectivity of the analyses compared to established processes. The method has now been further developed so that even smaller laboratories can benefit from this freely accessible machine learning method – an important step towards clinical practice. The study has now been published in the journal "Patterns".

ABSTRACT Typical state of the art flow cytometry data samples consists of measures of more than 100.000 cells in 10 or more features. AI systems are able to diagnose such data with almost the same accuracy as human experts. However, there is one central challenge in such systems: their decisions have far-reaching consequences for the health and life of people, and therefore, the decisions of AI systems need to be understandable and justifiable by humans. In this work, we present a novel explainable AI method, called ALPODS, which is able to classify (diagnose) cases based on clusters, i.e., subpopulations, in the high-dimensional data. ALPODS is able to explain its decisions in a form that is understandable for human experts. For the identified subpopulations, fuzzy reasoning rules expressed in the typical language of domain experts are generated. A visualization method based on these rules allows human experts to understand the reasoning used by the AI system. A comparison to a selection of state of the art explainable AI systems shows that ALPODS operates efficiently on known benchmark data and also on everyday routine case data. KEYWORDS: Explainable AI, Expert System, Symbolic System, Biomedical Data 1. INTRODUCTION State of the art machine learning (ML) artificial intelligence (AI) algorithms are effectively and efficiently able to diagnose (classify) high-dimensional data sets in modern medicine, e.g., for multiparameter flow cytometry data [Hu et al., 2019; Zhao et al., 2020]. These are systems that, after a training (learning) phase using learning data, perform well on data that are not part of the training data, i.e., the test data. This is called supervised learning [Murphy, 2012].

Analysis of flow cytometry data is an essential tool for clinical diagnosis of hematological and immunological conditions. Current clinical workflows rely on a manual process called gating to classify cells into their canonical types. This dependence on human annotation limits the rate, reproducibility, and complexity of flow cytometry analysis. In this paper, we propose using Mondrian processes to perform automated gating by incorporating prior information of the kind used by gating technicians. The method segments cells into types via Bayesian nonparametric trees. Examining the posterior over trees allows for interpretable visualizations and uncertainty quantification - two vital qualities for implementation in clinical practice.