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Register a new userInformation Preserving Component Analysis: Data Projections for Flow Cytometry Analysis
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Kevin Carter
Publication date
2008
fields
Mathematical Statistics
and research's language is
English
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Flow cytometry is often used to characterize the malignant cells in leukemia and lymphoma patients, traced to the level of the individual cell. Typically, flow cytometric data analysis is performed through a series of 2-dimensional projections onto the axes of the data set. Through the years, clinicians have determined combinations of different fluorescent markers which generate relatively known expression patterns for specific subtypes of leukemia and lymphoma -- cancers of the hematopoietic system. By only viewing a series of 2-dimensional projections, the high-dimensional nature of the data is rarely exploited. In this paper we present a means of determining a low-dimensional projection which maintains the high-dimensional relationships (i.e. information) between differing oncological data sets. By using machine learning techniques, we allow clinicians to visualize data in a low dimension defined by a linear combination of all of the available markers, rather than just 2 at a time. This provides an aid in diagnosing similar forms of cancer, as well as a means for variable selection in exploratory flow cytometric research. We refer to our method as Information Preserving Component Analysis (IPCA).
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Compositional data represent a specific family of multivariate data, where the information of interest is contained in the ratios between parts rather than in absolute values of single parts. The analysis of such specific data is challenging as the application of standard multivariate analysis tools on the raw observations can lead to spurious results. Hence, it is appropriate to apply certain transformations prior further analysis. One popular multivariate data analysis tool is independent component analysis. Independent component analysis aims to find statistically independent components in the data and as such might be seen as an extension to principal component analysis. In this paper we examine an approach of how to apply independent component analysis on compositional data by respecting the nature of the former and demonstrate the usefulness of this procedure on a metabolomic data set.
Flow cytometry is a technology that rapidly measures antigen-based markers associated to cells in a cell population. Although analysis of flow cytometry data has traditionally considered one or two markers at a time, there has been increasing interest in multidimensional analysis. However, flow cytometers are limited in the number of markers they can jointly observe, which is typically a fraction of the number of markers of interest. For this reason, practitioners often perform multiple assays based on different, overlapping combinations of markers. In this paper, we address the challenge of imputing the high dimensional jointly distributed values of marker attributes based on overlapping marginal observations. We show that simple nearest neighbor based imputation can lead to spurious subpopulations in the imputed data, and introduce an alternative approach based on nearest neighbor imputation restricted to a cells subpopulation. This requires us to perform clustering with missing data, which we address with a mixture model approach and novel EM algorithm. Since mixture model fitting may be ill-posed, we also develop techniques to initialize the EM algorithm using domain knowledge. We demonstrate our approach on real flow cytometry data.
The robust PCA of covariance matrices plays an essential role when isolating key explanatory features. The currently available methods for performing such a low-rank plus sparse decomposition are matrix specific, meaning, those algorithms must re-run for every new matrix. Since these algorithms are computationally expensive, it is preferable to learn and store a function that instantaneously performs this decomposition when evaluated. Therefore, we introduce Denise, a deep learning-based algorithm for robust PCA of covariance matrices, or more generally of symmetric positive semidefinite matrices, which learns precisely such a function. Theoretical guarantees for Denise are provided. These include a novel universal approximation theorem adapted to our geometric deep learning problem, convergence to an optimal solution of the learning problem and convergence of the training scheme. Our experiments show that Denise matches state-of-the-art performance in terms of decomposition quality, while being approximately 2000x faster than the state-of-the-art, PCP, and 200x faster than the current speed optimized method, fast PCP.
Acceleration in symbolic verification consists in computing the exact effect of some control-flow loops in order to speed up the iterative fix-point computation of reachable states. Even if no termination guarantee is provided in theory, successful results were obtained in practice by different tools implementing this framework. In this paper, the acceleration framework is extended to data-flow analysis. Compared to a classical widening/narrowing-based abstract interpretation, the loss of precision is controlled here by the choice of the abstract domain and does not depend on the way the abstract value is computed. Our approach is geared towards precision, but we dont loose efficiency on the way. Indeed, we provide a cubic-time acceleration-based algorithm for solving interval constraints with full multiplication.
Modern machine learning methods are critical to the development of large-scale personalized learning systems that cater directly to the needs of individual learners. The recently developed SPARse Factor Analysis (SPARFA) framework provides a new statistical model and algorithms for machine learning-based learning analytics, which estimate a learners knowledge of the latent concepts underlying a domain, and content analytics, which estimate the relationships among a collection of questions and the latent concepts. SPARFA estimates these quantities given only the binary-valued graded responses to a collection of questions. In order to better interpret the estimated latent concepts, SPARFA relies on a post-processing step that utilizes user-defined tags (e.g., topics or keywords) available for each question. In this paper, we relax the need for user-defined tags by extending SPARFA to jointly process both graded learner responses and the text of each question and its associated answer(s) or other feedback. Our purely data-driven approach (i) enhances the interpretability of the estimated latent concepts without the need of explicitly generating a set of tags or performing a post-processing step, (ii) improves the prediction performance of SPARFA, and (iii) scales to large test/assessments where human annotation would prove burdensome. We demonstrate the efficacy of the proposed approach on two real educational datasets.
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