Topological Feature Extraction for Interpretable Cancer Tissue Classification

An Artificial Intelligence Ultrasound Platform for Screening and Staging of Thyroid Cancer

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is currently diagnosed by a diagnostic interview, mainly based on subjective reports from parents or teachers. It is necessary to develop methods that rely on objectively measureable neurobiological data to assess brain-behavior relationship in patients with ADHD. We investigated the application of a topological data analysis tool, Mapper, to analyze the brain functional connectivity data from ADHD patients.MethodsTo quantify the disease severity using the neuroimaging data, the decomposition of individual functional networks into normal and disease components by the healthy state model (HSM) was performed, and the magnitude of the disease component (MDC) was computed. Topological data analysis using Mapper was performed to distinguish children with ADHD (n = 196) from typically developing controls (TDC) (n = 214).ResultsIn the topological data analysis, the partial clustering results of patients with ADHD and normal subjects were shown in a chain-like graph. In the correlation analysis, the MDC showed a significant increase with lower intelligence scores in TDC. We also found that the rates of comorbidity in ADHD significantly increased when the deviation of the functional connectivity from HSM was large. In addition, a significant correlation between ADHD symptom severity and MDC was found in part of the dataset.ConclusionsThe application of HSM and topological data analysis methods in assessing the brain functional connectivity seem to be promising tools to quantify ADHD symptom severity and to reveal the hidden relationship between clinical phenotypic variables and brain connectivity.

An approach to extract topological information from Intuitionistic Fuzzy Sets and their application in obtaining a Natural Hierarchical Clustering Algorithm

Glioblastoma multiforme (GBM) is a fast-growing and highly invasive brain tumor, which tends to occur in adults between the ages of 45 and 70 and it accounts for 52 percent of all primary brain tumors. Usually, GBMs are detected by magnetic resonance images (MRI). Among MRI, a fluid-attenuated inversion recovery (FLAIR) sequence produces high quality digital tumor representation. Fast computer-aided detection and segmentation techniques are needed for overcoming subjective medical doctors (MDs) judgment. This study has three main novelties for demonstrating the role of topological features as new set of radiomics features which can be used as pillars of a personalized diagnostic systems of GBM analysis from FLAIR. For the first time topological data analysis is used for analyzing GBM from three complementary perspectives—tumor growth at cell level, temporal evolution of GBM in follow-up period and eventually GBM detection. The second novelty is represented by the definition of a new Shannon-like topological entropy, the so-called Generator Entropy. The third novelty is the combination of topological and textural features for training automatic interpretable machine learning. These novelties are demonstrated by three numerical experiments. Topological Data Analysis of a simplified 2D tumor growth mathematical model had allowed to understand the bio-chemical conditions that facilitate tumor growth—the higher the concentration of chemical nutrients the more virulent the process. Topological data analysis was used for evaluating GBM temporal progression on FLAIR recorded within 90 days following treatment completion and at progression. The experiment had confirmed that persistent entropy is a viable statistics for monitoring GBM evolution during the follow-up period. In the third experiment we developed a novel methodology based on topological and textural features and automatic interpretable machine learning for automatic GBM classification on FLAIR. The algorithm reached a classification accuracy up to 97%.

Topological Data Analysis (TDA) is used to extract topological features such as rings from point clouds. Recent works have identified that existing methods, which construct persistence diagrams in TDA, are not robust to noise and varied densities in a point cloud. This causes these methods to obtain incorrect topological features. We analyze the necessary properties of an approach that can address these two issues, and propose a new filter function for TDA based on a new data-dependent kernel that possesses these properties. Our empirical evaluation reveals that (i) the proposed kernel provides a better mean for UMAP dimensionality reduction (ii) the proposed filter function can significantly improve the performance of Topological Point Cloud Clustering (iii) the proposed filter function is a more effective way of constructing Persistence Diagram for t-SNE visualization and SVM classification than three existing methods of TDA, In addition, we explore the proposed filter’s performance on a more complex deformation named Riemannian stretching. Our proposed filter equipped with Sample Fermat distance outperforms all the other filters when noise and Riemannian stretching coexist. Code is available at https://github.com/IsolationKernel/Codes/tree/main/Lambda-kernel.

<p>Over the last few years, the amount of large and complex data in the public domain has increased enormously and new challenges arose in the representation, analysis and visualization of such data. Considering the number of space missions that provided and will provide remote sensing data, there is still the need of a system that can be dispatched in several remote repositories and being accessible from a single client of commodity hardware.</p><p>To tackle this challenge, at the DLR Institute for Software Technology we have defined a dual backend frontend system, enabling the interactive analysis and visualization of large-scale remote sensing data. The basis for all visualization and interaction approaches is CosmoScout VR, a visualization tool developed internally at DLR, and publicly available on Github, that allows the visualization of complex planetary data and large simulation data in real-time. The dual component of this system is based on an MPI framework, called Viracocha, that enables the analysis of large data remotely, and allows the efficient network usage about sending compact and partial results for interactive visualization in CosmoScout as soon as they are computed.</p><p>A node-based interface is defined within the visualization tool, and this lets a domain expert to easily define customized pipelines for processing and visualizing the remote data. Each “node” of this interface is either linked with a feature extraction module, defined in Viracocha, or to a rendering module defined directly in CosmoScout. Being this interface completely customizable by a user, multiple pipelines can be defined over the same dataset to enhance even more the visualization feedback for analysis purposes.</p><p>Being an ongoing project, on top of these tools, as a novel strategy in EO data processing and visualization, we plan to define and implement strategies based on Topological Data Analysis (TDA). TDA is an emerging set of technique for processing the data considering its topological features. These include both the geometric information associated to a point, as well all the non-geometric scalar values, like temperature and pressure, to name a few, that can be captured during a monitoring mission. One of the major theories behind TDA is Discrete Morse Theory, that, given a scalar value, is used to define a gradient on such function, extract the critical points, identify the region-of-influence of each critical point, and so on. This strategy is parameter free and enables a domain scientist to process large datasets without a prior knowledge of it.</p><p>An interesting research question, that it will be investigated during this project is the correlation of changes of critical points at different time steps, and the identification of deformation (or changes) across time in the original dataset.</p>

Diagnosing neuropsychiatric systemic lupus erythematosus (NPSLE) and differentiating it from systemic lupus erythematosus (SLE) without neuropsychiatric manifestations remains a substantial clinical challenge due to the absence of specific biomarkers. Topological data analysis (TDA) is a novel computational technique that enables the visualization, exploration, and analysis of complex data structures. This study aimed to identify distinct neuroimaging biomarkers in patients with NPSLE (NPSLE group) and differentiate them from patients with SLE without neuropsychiatric symptoms (non-NPSLE group) by employing TDA. We conducted a retrospective cohort study involving 30 patients with NPSLE and 30 without neuropsychiatric symptoms between 2005 and 2020. TDA was utilized to extract topological features, specifically connected components and holes, from fluid-attenuated inversion recovery (FLAIR) sequences obtained via brain magnetic resonance imaging (MRI). Summary statistics, including critical point count, persistence lifetime, centroid coordinates, perimeter, area, and filamentarity, were derived from persistence diagrams. Multiple logistic regression analyses, adjusted for age, cerebrovascular comorbidities, and 50% hemolytic unit of complement levels, demonstrated a significant association between NPSLE and the perimeter of the holes (odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.07-2.63, p = 0.025) and the area of the holes (OR: 4.42, 95% CI: 1.35-19.6, p = 0.026) of the identified topological features. Additionally, both areas under the receiver operating characteristic curve (AUC) exceeded 0.8, indicating good diagnostic accuracy. This study identified novel neuroimaging biomarkers for the diagnosis of NPSLE. The application of TDA to brain MRI features in patients with SLE proved to be a valuable diagnostic tool, particularly through the analysis of persistence diagrams.

Topological data analysis (TDA) is a mathematically well-founded set of methods to derive robust information about the structure and topology of data. It has been applied successfully in several biological contexts. Derived primarily from algebraic topology, TDA rigorously identifies persistent features in complex data, making it well-suited to better understand the key features of three-dimensional chromosome structure. Chromosome structure has a significant influence in many diverse genomic processes and has recently been shown to relate to cellular differentiation. While there exist many methods to study specific substructures of chromosomes, we are still missing a global view of all geometric features of chromosomes. By applying TDA to the study of chromosome structure through differentiation across three cell lines, we provide insight into principles of chromosome folding and looping. We identify persistent connected components and one-dimensional topological features of chromosomes and characterize them across cell types and stages of differentiation. Availability: Scripts to reproduce the results from this study can be found at https://github.com/Kingsford-Group/hictda

Recent developments of molecular biology have revealed diverse mechanisms of skin diseases, and precision medicine considering these mechanisms requires the frequent objective evaluation of skin phenotypes. Transepidermal water loss (TEWL) is commonly used for evaluating skin barrier function; however, direct measurement of TEWL is time-consuming and is not convenient for daily clinical practice. Here, we propose a new skin barrier assessment method using skin images with topological data analysis (TDA). TDA enabled efficient identification of structural features from a skin image taken by a microscope. These features reflected the regularity of the skin texture. We found a significant correlation between the topological features and TEWL. Moreover, using the features as input, we trained machine-learning models to predict TEWL and obtained good accuracy (R2 = 0.524). Our results suggest that assessment of skin barrier function by topological image analysis is promising.

BOLD-based fMRI is the most widely used method for studying brain function. The BOLD signal while valuable, is beset with unique vulnerabilities. The most notable of these is the modest signal to noise ratio, and the relatively low temporal and spatial resolution. However, the high dimensional complexity of the BOLD signal also presents unique opportunities for functional discovery. Topological Data Analyses (TDA), a branch of mathematics optimized to search for specific classes of structure within high dimensional data may provide particularly valuable applications. In this investigation, we acquired fMRI data in the anterior cingulate cortex (ACC) using a basic motor control paradigm. Then, for each participant and each of three task conditions, fMRI signals in the ACC were summarized using two methods: a) TDA based methods of persistent homology and persistence landscapes and b) non-TDA based methods using a standard vectorization scheme. Finally, using machine learning (with support vector classifiers), classification accuracy of TDA and non-TDA vectorized data was tested across participants. In each participant, TDA-based classification out-performed the non-TDA based counterpart, suggesting that our TDA analytic pipeline better characterized task- and condition-induced structure in fMRI data in the ACC. Our results emphasize the value of TDA in characterizing task- and condition-induced structure in regional fMRI signals. In addition to providing our analytical tools for other users to emulate, we also discuss the unique role that TDA-based methods can play in the study of individual differences in the structure of functional brain signals in the healthy and the clinical brain.

The recent adoption of artificial intelligence (AI) in robotics has driven the development of algorithms that enable autonomous systems to adapt to complex social environments. In particular, safe and efficient social navigation is a key challenge, requiring AI not only to avoid collisions and deadlocks but also to interact intuitively and predictably with its surroundings. To date, methods based on probabilistic models and the generation of conformal safety regions have shown promising results in defining safety regions with a controlled margin of error, primarily relying on classification approaches and explicit rules to describe collision-free navigation conditions. This work extends the existing perspective by investigating how topological features can contribute to the creation of explainable safety regions in social navigation scenarios, enabling the classification and characterization of different simulation behaviors. Rather than relying on behaviors parameters to generate safety regions, we leverage topological features through topological data analysis. We first utilize global rule-based classification to provide interpretable characterizations of different simulation behaviors, distinguishing between safe (free of collisions) and unsafe scenarios based on topological properties. Next, we define safety regions, $$S_\varepsilon $$ S ε , representing zones in the topological feature space where collisions are avoided with a maximum classification error of $$\varepsilon $$ ε . These regions are constructed using adjustable SVM classifiers and order statistics, ensuring a robust and scalable decision boundary. To enhance interpretability, we extract local rules from these safety regions, ensuring that the decision-making process remains transparent and comprehensible. Initially, we generate safety regions that separate simulations with and without collisions, achieving higher accuracy than methods that do not incorporate topological features. This approach also provides a deeper and more intuitive understanding of robot interactions within a navigable space. We then extend our methodology to design safety regions that ensure efficient simulations (i.e., free of deadlocks). Finally, we integrate both aspects to obtain comprehensive safety regions that guarantee both collision-free and deadlock-free simulations, defining an overall compliant simulation space.

Single-cell technologies have revolutionized our ability to interrogate biological systems at unprecedented resolution, revealing complex cellular heterogeneity and dynamic processes that underlie development, disease, and immune responses. However, the high dimensionality and nonlinear structure of single-cell data present substantial analytical challenges. Topological data analysis offers a powerful mathematical framework for capturing the intrinsic shape of data, providing novel insights that complement and extend traditional statistical and machine learning methods. By leveraging tools such as persistent homology and the Mapper algorithm, TDA enables the detection of subtle, multiscale patterns – including rare cell populations, transitional states, and branching trajectories – that are often obscured by conventional approaches. In this review, we explore the theoretical foundations of topological data analysis and examine its emerging applications across single-cell transcriptomics, proteomics, and spatial biology. We highlight how this approach can unveil previously unrecognized biological phenomena, from alternative differentiation paths to complex tissue architectures, and discuss the growing ecosystem of computational tools that support its use. As single-cell datasets become increasingly large and multimodal, topological data analysis stands out as a uniquely robust and interpretable approach, with the potential to deepen our understanding of cellular identity and function in health and disease. TDA is specially suited for fields such as systems immunology since it can capture the complex, nonlinear structures inherent in high-dimensional immune data helping to identify distinct immune cell states, differentiation pathways, and dynamic responses to infection or therapy. This topological perspective complements traditional statistical approaches, providing a robust, scale-invariant framework for uncovering hidden organization within the immune system’s complexity.

In this paper we develop an alternative topological data analysis (TDA) approach for studying graph representations of time series of dynamical systems. Specifically, we show how persistent homology, a tool from TDA, can be used to yield a compressed, multi-scale representation of the graph that can distinguish between dynamic states such as periodic and chaotic behavior. We show the approach for two graph constructions obtained from the time series. In the first approach the time series is embedded into a point cloud which is then used to construct an undirected k-nearest-neighbor graph. The second construct relies on the recently developed ordinal partition framework. In either case, a pairwise distance matrix is then calculated using the shortest path between the graph's nodes, and this matrix is utilized to define a filtration of a simplicial complex that enables tracking the changes in homology classes over the course of the filtration. These changes are summarized in a persistence diagram's two-dimensional summary of changes in the topological features. We then extract existing as well as new geometric and entropy point summaries from the persistence diagram and compare to other commonly used network characteristics. Our results show that persistence-based point summaries yield a clearer distinction of the dynamic behavior and are more robust to noise than existing graph-based scores, especially when combined with ordinal graphs.

Topological data analysis (TDA) is an active field of mathematics for quantifying shape in complex data. Standard methods in TDA such as persistent homology (PH) are typically focused on the analysis of data consisting of a single entity (e.g., cells or molecular species). However, state-of-the-art data collection techniques now generate exquisitely detailed multispecies data, prompting a need for methods that can examine and quantify the relations among them. Such heterogeneous data types arise in many contexts, ranging from biomedical imaging, geospatial analysis, to species ecology. Here, we propose two methods for encoding spatial relations among different data types that are based on Dowker complexes and Witness complexes. We apply the methods to synthetic multispecies data of a tumor microenvironment and analyze topological features that capture relations between different cell types, e.g., blood vessels, macrophages, tumor cells, and necrotic cells. We demonstrate that relational topological features can extract biological insight, including the dominant immune cell phenotype (an important predictor of patient prognosis) and the parameter regimes of a data-generating model. The methods provide a quantitative perspective on the relational analysis of multispecies spatial data, overcome the limits of traditional PH, and are readily computable.

Persistent homology is a powerful tool in topological data analysis (TDA) to compute, study and encode efficiently multi-scale topological features and is being increasingly used in digital image classification. The topological features represent number of connected components, cycles, and voids that describe the shape of data. Persistent homology extracts the birth and death of these topological features through a filtration process. The lifespan of these features can represented using persistent diagrams (topological signatures). Cubical homology is a more efficient method for extracting topological features from a 2D image and uses a collection of cubes to compute the homology, which fits the digital image structure of grids. In this research, we propose a cubical homology-based algorithm for extracting topological features from 2D images to generate their topological signatures. Additionally, we propose a score, which measures the significance of each of the sub-simplices in terms of persistence. Also, gray level co-occurrence matrix (GLCM) and contrast limited adapting histogram equalization (CLAHE) are used as a supplementary method for extracting features. Machine learning techniques are then employed to classify images using the topological signatures. Among the eight tested algorithms with six published image datasets with varying pixel sizes, classes, and distributions, our experiments demonstrate that cubical homology-based machine learning with deep residual network (ResNet 1D) and Light Gradient Boosting Machine (lightGBM) shows promise with the extracted topological features.