Partially-observed models for classifying minerals on Mars

The identification of phyllosilicates by NASA's CRISM (Compact Reconnaissance Imaging Spectrometer for Mars) strongly suggests the presence of water-related geological processes. A variety of water-bearing phyllosilicate minerals have already been identified by several research groups utilizing spectral enrichment techniques and matching phyllosilicate-rich regions on the Martian surface to known spectra of minerals found on earth. However, fully automated analysis of the CRISM data remains a challenge for two main reasons. First, there is significant variability in the spectral signature of the same mineral obtained from different regions on the Martian surface. Second, the list of mineral confirmed to date constituting the set of training classes is not exhaustive. Thus, when classifying new regions, using a classifier trained with selected minerals and chemicals, one must consider the potential presence of unknown materials not represented in the training library. We made an initial attempt to study these problems in the context of our recent work on partially-observed classification models and present results that show the utility of such models in identifying spectra of unknown minerals while simultaneously recognizing spectra of known minerals

The Infinite Mixture of Infinite Gaussian Mixtures

Dirichlet process mixture of Gaussians (DPMG) has been used in the literature for clustering and density estimation problems. However, many real-world data exhibit cluster distributions that cannot be captured by a single Gaussian. Modeling such data sets by DPMG creates several extraneous clusters even when clusters are relatively well-defined. Herein, we present the infinite mixture of infinite Gaussian mixtures (I2GMM) for more flexible modeling of data sets with skewed and multi-modal cluster distributions. Instead of using a single Gaussian for each cluster as in the standard DPMG model, the generative model of I2GMM uses a single DPMG for each cluster. The individual DPMGs are linked together through centering of their base distributions at the atoms of a higher level DP prior. Inference is performed by a collapsed Gibbs sampler that also enables partial parallelization. Experimental results on several artificial and real-world data sets suggest the proposed I2GMM model can predict clusters more accurately than existing variational Bayes and Gibbs sampler versions of DPMG

A non-parametric Bayesian model for joint cell clustering and cluster matching: identification of anomalous sample phenotypes with random effects

BACKGROUND: Flow cytometry (FC)-based computer-aided diagnostics is an emerging technique utilizing modern multiparametric cytometry systems.The major difficulty in using machine-learning approaches for classification of FC data arises from limited access to a wide variety of anomalous samples for training. In consequence, any learning with an abundance of normal cases and a limited set of specific anomalous cases is biased towards the types of anomalies represented in the training set. Such models do not accurately identify anomalies, whether previously known or unknown, that may exist in future samples tested. Although one-class classifiers trained using only normal cases would avoid such a bias, robust sample characterization is critical for a generalizable model. Owing to sample heterogeneity and instrumental variability, arbitrary characterization of samples usually introduces feature noise that may lead to poor predictive performance. Herein, we present a non-parametric Bayesian algorithm called ASPIRE (anomalous sample phenotype identification with random effects) that identifies phenotypic differences across a batch of samples in the presence of random effects. Our approach involves simultaneous clustering of cellular measurements in individual samples and matching of discovered clusters across all samples in order to recover global clusters using probabilistic sampling techniques in a systematic way. RESULTS: We demonstrate the performance of the proposed method in identifying anomalous samples in two different FC data sets, one of which represents a set of samples including acute myeloid leukemia (AML) cases, and the other a generic 5-parameter peripheral-blood immunophenotyping. Results are evaluated in terms of the area under the receiver operating characteristics curve (AUC). ASPIRE achieved AUCs of 0.99 and 1.0 on the AML and generic blood immunophenotyping data sets, respectively. CONCLUSIONS: These results demonstrate that anomalous samples can be identified by ASPIRE with almost perfect accuracy without a priori access to samples of anomalous subtypes in the training set. The ASPIRE approach is unique in its ability to form generalizations regarding normal and anomalous states given only very weak assumptions regarding sample characteristics and origin. Thus, ASPIRE could become highly instrumental in providing unique insights about observed biological phenomena in the absence of full information about the investigated samples

Automated assessment of disease progression in Acute Myeloid Leukemia by probabilistic analysis of flow cytometry data

Objective: Flow cytometry (FC) is a widely acknowledged technology in diagnosis of acute myeloid leukemia (AML) and has been indispensable in determining progression of the disease. Although FC plays a key role as a post-therapy prognosticator and evaluator of therapeutic efficacy, the manual analysis of cytometry data is a barrier to optimization of reproducibility and objectivity. This study investigates the utility of our recently introduced non-parametric Bayesian framework in accurately predicting the direction of change in disease progression in AML patients using FC data. Methods: The highly flexible non-parametric Bayesian model based on the infinite mixture of infinite Gaussian mixtures is used for jointly modeling data from multiple FC samples to automatically identify functionally distinct cell populations and their local realizations. Phenotype vectors are obtained by characterizing each sample by the proportions of recovered cell populations, which are in turn used to predict the direction of change in disease progression for each patient. Results: We used 200 diseased and non-diseased immunophenotypic panels for training and tested the system with 36 additional AML cases collected at multiple time points. The proposed framework identified the change in direction of disease progression with accuracies of 90% (9 out of 10) for relapsing cases and 100% (26 out of 26) for the remaining cases. Conclusions: We believe that these promising results are an important first step towards the development of automated predictive systems for disease monitoring and continuous response evaluation. Significance: Automated measurement and monitoring of therapeutic response is critical not only for objective evaluation of disease status prognosis but also for timely assessment of treatment strategies

Simplicity of Kmeans versus Deepness of Deep Learning: A Case of Unsupervised Feature Learning with Limited Data

We study a bio-detection application as a case study to demonstrate that Kmeans -- based unsupervised feature learning can be a simple yet effective alternative to deep learning techniques for small data sets with limited intra-as well as inter-class diversity. We investigate the effect on the classifier performance of data augmentation as well as feature extraction with multiple patch sizes and at different image scales. Our data set includes 1833 images from four different classes of bacteria, each bacterial culture captured at three different wavelengths and overall data collected during a three-day period. The limited number and diversity of images present, potential random effects across multiple days, and the multi-mode nature of class distributions pose a challenging setting for representation learning. Using images collected on the first day for training, on the second day for validation, and on the third day for testing Kmeans -- based representation learning achieves 97% classification accuracy on the test data. This compares very favorably to 56% accuracy achieved by deep learning and 74% accuracy achieved by handcrafted features. Our results suggest that data augmentation or dropping connections between units offers little help for deep-learning algorithms, whereas significant boost can be achieved by Kmeans -- based representation learning by augmenting data and by concatenating features obtained at multiple patch sizes or image scales

Lipidomic Profiling of the Epidermis in a Mouse Model of Dermatitis Reveals Sexual Dimorphism and Changes in Lipid Composition before the Onset of Clinical Disease.

Atopic dermatitis (AD) is a multifactorial disease associated with alterations in lipid composition and organization in the epidermis. Multiple variants of AD exist with different outcomes in response to therapies. The evaluation of disease progression and response to treatment are observational assessments with poor inter-observer agreement highlighting the need for molecular markers. SHARPIN-deficient mice (Sharpincpdm) spontaneously develop chronic proliferative dermatitis with features similar to AD in humans. To study the changes in the epidermal lipid-content during disease progression, we tested 72 epidermis samples from three groups (5-, 7-, and 10-weeks old) of cpdm mice and their WT littermates. An agnostic mass-spectrometry strategy for biomarker discovery termed multiple-reaction monitoring (MRM)-profiling was used to detect and monitor 1,030 lipid ions present in the epidermis samples. In order to select the most relevant ions, we utilized a two-tiered filter/wrapper feature-selection strategy. Lipid categories were compressed, and an elastic-net classifier was used to rank and identify the most predictive lipid categories for sex, phenotype, and disease stages of cpdm mice. The model accurately classified the samples based on phospholipids, cholesteryl esters, acylcarnitines, and sphingolipids, demonstrating that disease progression cannot be defined by one single lipid or lipid category

Generative modeling of the enteric nervous system employing point pattern analysis and graph construction

We describe a generative network model of the architecture of the enteric nervous system (ENS) in the colon employing data from images of human and mouse tissue samples obtained through confocal microscopy. Our models combine spatial point pattern analysis with graph generation to characterize the spatial and topological properties of the ganglia (clusters of neurons and glial cells), the inter-ganglionic connections, and the neuronal organization within the ganglia. We employ a hybrid hardcore-Strauss process for spatial patterns and a planar random graph generation for constructing the spatially embedded network. We show that our generative model may be helpful in both basic and translational studies, and it is sufficiently expressive to model the ENS architecture of individuals who vary in age and health status. Increased understanding of the ENS connectome will enable the use of neuromodulation strategies in treatment and clarify anatomic diagnostic criteria for people with bowel motility disorders.Comment: 17 pages, 5 figure