arXiv subjects

Charles M. Perou

Publications and source records attributed to Charles M. Perou.

6 recordsLinked to original sources

arXiv2022

Pairwise Nonlinear Dependence Analysis of Genomic Data

In The Cancer Genome Atlas (TCGA) data set, there are many interesting nonlinear dependencies between pairs of genes that reveal important relationships and subtypes of cancer. Such genomic data analysis requires a rapid, powerful and interpretable detection process, especially in a high-dimensional environment. We study the nonlinear patterns among the expression of pairs of genes from TCGA using a powerful tool called Binary Expansion Testing. We find many nonlinear patterns, some of which are driven by known cancer subtypes, some of which are novel.

stat.AP↗

arXiv2020

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.

q-bio.QM↗

arXiv2019

Deep Multi-View Learning via Task-Optimal CCA

Canonical Correlation Analysis (CCA) is widely used for multimodal data analysis and, more recently, for discriminative tasks such as multi-view learning; however, it makes no use of class labels. Recent CCA methods have started to address this weakness but are limited in that they do not simultaneously optimize the CCA projection for discrimination and the CCA projection itself, or they are linear only. We address these deficiencies by simultaneously optimizing a CCA-based and a task objective in an end-to-end manner. Together, these two objectives learn a non-linear CCA projection to a shared latent space that is highly correlated and discriminative. Our method shows a significant improvement over previous state-of-the-art (including deep supervised approaches) for cross-view classification, regularization with a second view, and semi-supervised learning on real data.

cs.LG↗

arXiv2018

Receiver Operating Characteristic Curves and Confidence Bands for Support Vector Machines

Many problems that appear in biomedical decision making, such as diagnosing disease and predicting response to treatment, can be expressed as binary classification problems. The costs of false positives and false negatives vary across application domains and receiver operating characteristic (ROC) curves provide a visual representation of this trade-off. Nonparametric estimators for the ROC curve, such as a weighted support vector machine (SVM), are desirable because they are robust to model misspecification. While weighted SVMs have great potential for estimating ROC curves, their theoretical properties were heretofore underdeveloped. We propose a method for constructing confidence bands for the SVM ROC curve and provide the theoretical justification for the SVM ROC curve by showing that the risk function of the estimated decision rule is uniformly consistent across the weight parameter. We demonstrate the proposed confidence band method and the superior sensitivity and specificity of the weighted SVM compared to commonly used methods in diagnostic medicine using simulation studies. We present two illustrative examples: diagnosis of hepatitis C and a predictive model for treatment response in breast cancer.

stat.ML↗

arXiv2018

Multiple Instance Learning for Heterogeneous Images: Training a CNN for Histopathology

Multiple instance (MI) learning with a convolutional neural network enables end-to-end training in the presence of weak image-level labels. We propose a new method for aggregating predictions from smaller regions of the image into an image-level classification by using the quantile function. The quantile function provides a more complete description of the heterogeneity within each image, improving image-level classification. We also adapt image augmentation to the MI framework by randomly selecting cropped regions on which to apply MI aggregation during each epoch of training. This provides a mechanism to study the importance of MI learning. We validate our method on five different classification tasks for breast tumor histology and provide a visualization method for interpreting local image classifications that could lead to future insights into tumor heterogeneity.

cs.CV↗

arXiv2009

Finding large average submatrices in high dimensional data

The search for sample-variable associations is an important problem in the exploratory analysis of high dimensional data. Biclustering methods search for sample-variable associations in the form of distinguished submatrices of the data matrix. (The rows and columns of a submatrix need not be contiguous.) In this paper we propose and evaluate a statistically motivated biclustering procedure (LAS) that finds large average submatrices within a given real-valued data matrix. The procedure operates in an iterative-residual fashion, and is driven by a Bonferroni-based significance score that effectively trades off between submatrix size and average value. We examine the performance and potential utility of LAS, and compare it with a number of existing methods, through an extensive three-part validation study using two gene expression datasets. The validation study examines quantitative properties of biclusters, biological and clinical assessments using auxiliary information, and classification of disease subtypes using bicluster membership. In addition, we carry out a simulation study to assess the effectiveness and noise sensitivity of the LAS search procedure. These results suggest that LAS is an effective exploratory tool for the discovery of biologically relevant structures in high dimensional data. Software is available at https://genome.unc.edu/las/.

q-bio.GN↗