Distance-weighted Sinkhorn loss for Alzheimer's disease classification.

Traditional loss functions such as cross-entropy loss often quantify the penalty for each mis-classified training sample without adequately considering its distance from the ground truth class distribution in the feature space. Intuitively, the larger this distance is, the higher the penalty should be. With this observation, we propose a penalty called distance-weighted Sinkhorn (DWS) loss. For each mis-classified training sample (with predicted label A and true label B), its contribution to the DWS loss positively correlates to the distance the training sample needs to travel to reach the ground truth distribution of all the A samples. We apply the DWS framework with a neural network to classify different stages of Alzheimer's disease. Our empirical results demonstrate that the DWS framework outperforms the traditional neural network loss functions and is comparable or better to traditional machine learning methods, highlighting its potential in biomedical informatics and data science.

Class-Balanced Deep Learning with Adaptive Vector Scaling Loss for Dementia Stage Detection.

Alzheimer's disease (AD) leads to irreversible cognitive decline, with Mild Cognitive Impairment (MCI) as its prodromal stage. Early detection of AD and related dementia is crucial for timely treatment and slowing disease progression. However, classifying cognitive normal (CN), MCI, and AD subjects using machine learning models faces class imbalance, necessitating the use of balanced accuracy as a suitable metric. To enhance model performance and balanced accuracy, we introduce a novel method called VS-Opt-Net. This approach incorporates the recently developed vector-scaling (VS) loss into a machine learning pipeline named STREAMLINE. Moreover, it employs Bayesian optimization for hyperparameter learning of both the model and loss function. VS-Opt-Net not only amplifies the contribution of minority examples in proportion to the imbalance level but also addresses the challenge of generalization in training deep networks. In our empirical study, we use MRI-based brain regional measurements as features to conduct the CN vs MCI and AD vs MCI binary classifications. We compare the balanced accuracy of our model with other machine learning models and deep neural network loss functions that also employ class-balanced strategies. Our findings demonstrate that after hyperparameter optimization, the deep neural network using the VS loss function substantially improves balanced accuracy. It also surpasses other models in performance on the AD dataset. Moreover, our feature importance analysis highlights VS-Opt-Net's ability to elucidate biomarker differences across dementia stages.

Multi-Group Tensor Canonical Correlation Analysis.

Tensor Canonical Correlation Analysis (TCCA) is a commonly employed statistical method utilized to examine linear associations between two sets of tensor datasets. However, the existing TCCA models fail to adequately address the heterogeneity present in real-world tensor data, such as brain imaging data collected from diverse groups characterized by factors like sex and race. Consequently, these models may yield biased outcomes. In order to surmount this constraint, we propose a novel approach called Multi-Group TCCA (MG-TCCA), which enables the joint analysis of multiple subgroups. By incorporating a dual sparsity structure and a block coordinate ascent algorithm, our MG-TCCA method effectively addresses heterogeneity and leverages information across different groups to identify consistent signals. This novel approach facilitates the quantification of shared and individual structures, reduces data dimensionality, and enables visual exploration. To empirically validate our approach, we conduct a study focused on investigating correlations between two brain positron emission tomography (PET) modalities (AV-45 and FDG) within an Alzheimer's disease (AD) cohort. Our results demonstrate that MG-TCCA surpasses traditional TCCA in identifying sex-specific cross-modality imaging correlations. This heightened performance of MG-TCCA provides valuable insights for the characterization of multimodal imaging biomarkers in AD.

Preference matrix guided sparse canonical correlation analysis for mining brain imaging genetic associations in Alzheimer's disease.

Investigating the relationship between genetic variation and phenotypic traits is a key issue in quantitative genetics. Specifically for Alzheimer's disease, the association between genetic markers and quantitative traits remains vague while, once identified, will provide valuable guidance for the study and development of genetics-based treatment approaches. Currently, to analyze the association of two modalities, sparse canonical correlation analysis (SCCA) is commonly used to compute one sparse linear combination of the variable features for each modality, giving a pair of linear combination vectors in total that maximizes the cross-correlation between the analyzed modalities. One drawback of the plain SCCA model is that the existing findings and knowledge cannot be integrated into the model as priors to help extract interesting correlations as well as identify biologically meaningful genetic and phenotypic markers. To bridge this gap, we introduce preference matrix guided SCCA (PM-SCCA) that not only takes priors encoded as a preference matrix but also maintains computational simplicity. A simulation study and a real-data experiment are conducted to investigate the effectiveness of the model. Both experiments demonstrate that the proposed PM-SCCA model can capture not only genotype-phenotype correlation but also relevant features effectively.

Comparing Amyloid Imaging Normalization Strategies for Alzheimer's Disease Classification using an Automated Machine Learning Pipeline.

Amyloid imaging has been widely used in Alzheimer's disease (AD) diagnosis and biomarker discovery through detecting the regional amyloid plaque density. It is essential to be normalized by a reference region to reduce noise and artifacts. To explore an optimal normalization strategy, we employ an automated machine learning (AutoML) pipeline, STREAMLINE, to conduct the AD diagnosis binary classification and perform permutation-based feature importance analysis with thirteen machine learning models. In this work, we perform a comparative study to evaluate the prediction performance and biomarker discovery capability of three amyloid imaging measures, including one original measure and two normalized measures using two reference regions (i.e., the whole cerebellum and the composite reference region). Our AutoML results indicate that the composite reference region normalization dataset yields a higher balanced accuracy, and identifies more AD-related regions based on the fractioned feature importance ranking.

Exploring Automated Machine Learning for Cognitive Outcome Prediction from Multimodal Brain Imaging using STREAMLINE.

STREAMLINE is a simple, transparent, end-to-end automated machine learning (AutoML) pipeline for easily conducting rigorous machine learning (ML) modeling and analysis. The initial version is limited to binary classification. In this work, we extend STREAMLINE through implementing multiple regression-based ML models, including linear regression, elastic net, group lasso, and L21 norm. We demonstrate the effectiveness of the regression version of STREAMLINE by applying it to the prediction of Alzheimer's disease (AD) cognitive outcomes using multimodal brain imaging data. Our empirical results demonstrate the feasibility and effectiveness of the newly expanded STREAMLINE as an AutoML pipeline for evaluating AD regression models, and for discovering multimodal imaging biomarkers.

Fair Canonical Correlation Analysis.

This paper investigates fairness and bias in Canonical Correlation Analysis (CCA), a widely used statistical technique for examining the relationship between two sets of variables. We present a framework that alleviates unfairness by minimizing the correlation disparity error associated with protected attributes. Our approach enables CCA to learn global projection matrices from all data points while ensuring that these matrices yield comparable correlation levels to group-specific projection matrices. Experimental evaluation on both synthetic and real-world datasets demonstrates the efficacy of our method in reducing correlation disparity error without compromising CCA accuracy.

Fairness-Aware Class Imbalanced Learning on Multiple Subgroups.

We present a novel Bayesian-based optimization framework that addresses the challenge of generalization in overparameterized models when dealing with imbalanced subgroups and limited samples per subgroup. Our proposed tri-level optimization framework utilizes local predictors, which are trained on a small amount of data, as well as a fair and class-balanced predictor at the middle and lower levels. To effectively overcome saddle points for minority classes, our lower-level formulation incorporates sharpness-aware minimization. Meanwhile, at the upper level, the framework dynamically adjusts the loss function based on validation loss, ensuring a close alignment between the global predictor and local predictors. Theoretical analysis demonstrates the framework's ability to enhance classification and fairness generalization, potentially resulting in improvements in the generalization bound. Empirical results validate the superior performance of our tri-level framework compared to existing state-of-the-art approaches. The source code can be found at https://github.com/PennShenLab/FACIMS.