Joint and individual analysis of breast cancer histologic images and genomic covariates

A key challenge in modern data analysis is understanding connections between complex and differing modalities of data. For example, two of the main approaches to the study of breast cancer are histopathology (analyzing visual characteristics of tumors) and genetics. While histopathology is the gold standard for diagnostics and there have been many recent breakthroughs in genetics, there is little overlap between these two fields. We aim to bridge this gap by developing methods based on Angle-based Joint and Individual Variation Explained (AJIVE) to directly explore similarities and differences between these two modalities. Our approach exploits Convolutional Neural Networks (CNNs) as a powerful, automatic method for image feature extraction to address some of the challenges presented by statistical analysis of histopathology image data. CNNs raise issues of interpretability that we address by developing novel methods to explore visual modes of variation captured by statistical algorithms (e.g. PCA or AJIVE) applied to CNN features. Our results provide many interpretable connections and contrasts between histopathology and genetics

Transforming Feature Space to Interpret Machine Learning Models

Model-agnostic tools for interpreting machine-learning models struggle to summarize the joint effects of strongly dependent features in high-dimensional feature spaces, which play an important role in pattern recognition, for example in remote sensing of landcover. This contribution proposes a novel approach that interprets machine-learning models through the lens of feature space transformations. It can be used to enhance unconditional as well as conditional post-hoc diagnostic tools including partial dependence plots, accumulated local effects plots, or permutation feature importance assessments. While the approach can also be applied to nonlinear transformations, we focus on linear ones, including principal component analysis (PCA) and a partial orthogonalization technique. Structured PCA and diagnostics along paths offer opportunities for representing domain knowledge. The new approach is implemented in the R package `wiml`, which can be combined with existing explainable machine-learning packages. A case study on remote-sensing landcover classification with 46 features is used to demonstrate the potential of the proposed approach for model interpretation by domain experts.Comment: 13 pages, 7 figures, 1 tabl

Sparse Proteomics Analysis - A compressed sensing-based approach for feature selection and classification of high-dimensional proteomics mass spectrometry data

Background: High-throughput proteomics techniques, such as mass spectrometry (MS)-based approaches, produce very high-dimensional data-sets. In a clinical setting one is often interested in how mass spectra differ between patients of different classes, for example spectra from healthy patients vs. spectra from patients having a particular disease. Machine learning algorithms are needed to (a) identify these discriminating features and (b) classify unknown spectra based on this feature set. Since the acquired data is usually noisy, the algorithms should be robust against noise and outliers, while the identified feature set should be as small as possible. Results: We present a new algorithm, Sparse Proteomics Analysis (SPA), based on the theory of compressed sensing that allows us to identify a minimal discriminating set of features from mass spectrometry data-sets. We show (1) how our method performs on artificial and real-world data-sets, (2) that its performance is competitive with standard (and widely used) algorithms for analyzing proteomics data, and (3) that it is robust against random and systematic noise. We further demonstrate the applicability of our algorithm to two previously published clinical data-sets

APPLICATIONS OF MACHINE LEARNING IN MICROBIAL FORENSICS

Microbial ecosystems are complex, with hundreds of members interacting with each other and the environment. The intricate and hidden behaviors underlying these interactions make research questions challenging – but can be better understood through machine learning. However, most machine learning that is used in microbiome work is a black box form of investigation, where accurate predictions can be made, but the inner logic behind what is driving prediction is hidden behind nontransparent layers of complexity. Accordingly, the goal of this dissertation is to provide an interpretable and in-depth machine learning approach to investigate microbial biogeography and to use micro-organisms as novel tools to detect geospatial location and object provenance (previous known origin). These contributions follow with a framework that allows extraction of interpretable metrics and actionable insights from microbiome-based machine learning models. The first part of this work provides an overview of machine learning in the context of microbial ecology, human microbiome studies and environmental monitoring – outlining common practice and shortcomings. The second part of this work demonstrates a field study to demonstrate how machine learning can be used to characterize patterns in microbial biogeography globally – using microbes from ports located around the world. The third part of this work studies the persistence and stability of natural microbial communities from the environment that have colonized objects (vessels) and stay attached as they travel through the water. Finally, the last part of this dissertation provides a robust framework for investigating the microbiome. This framework provides a reasonable understanding of the data being used in microbiome-based machine learning and allows researchers to better apprehend and interpret results. Together, these extensive experiments assist an understanding of how to carry an in-silico design that characterizes candidate microbial biomarkers from real world settings to a rapid, field deployable diagnostic assay. The work presented here provides evidence for the use of microbial forensics as a toolkit to expand our basic understanding of microbial biogeography, microbial community stability and persistence in complex systems, and the ability of machine learning to be applied to downstream molecular detection platforms for rapid and accurate detection

A unique cardiac electrocardiographic 3D model. Toward interpretable AI diagnosis

Mathematical models of cardiac electrical activity are one of the most important tools for elucidating information about heart diagnostics. In this paper, we present an efficient mathematical formulation for this modeling simple enough to be easily parameterized and rich enough to provide realistic signals. It relies on a five dipole representation of the cardiac electric source, each one associated with the well-known waves of the electrocardiogram signal. Beyond the physical basis of the model, the parameters are physiologically interpretable as they characterize the wave shape, similar to what a physician would look for in signals, thus making them very useful in diagnosis. The model accurately reproduces the electrocardiogram signals of any diseased or healthy heart. This new discovery represents a significant advance in electrocardiography research. It is especially useful for diagnosis, patient follow-up or decision-making on new therapies; is also a promising tool for well-performing, transparent and interpretable AI approaches.The authors gratefully acknowledge the financial support received by the Spanish Ministry of Science, Innovation and Universities PID2019-106363RB-I00 to C.R., I.F. and Y.L. and by the Eugenio Rodríguez Pascual Foundation Biomedical Research Grants 2021 to I.F., Y.L., A.R-C., C.C. and C.R