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.

Deep Clustering Survival Machines with Interpretable Expert Distributions.

We develop deep clustering survival machines to simultaneously predict survival information and characterize data heterogeneity that is not typically modeled by conventional survival analysis methods. By modeling timing information of survival data generatively with a mixture of parametric distributions, referred to as expert distributions, our method learns weights of the expert distributions for individual instances based on their features discriminatively such that each instance's survival information can be characterized by a weighted combination of the learned expert distributions. Extensive experiments on both real and synthetic datasets have demonstrated that our method is capable of obtaining promising clustering results and competitive time-to-event predicting performance.

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.

Evaluate underdiagnosis and overdiagnosis bias of deep learning model on primary open-angle glaucoma diagnosis in under-served populations.

In the United States, primary open-angle glaucoma (POAG) is the leading cause of blindness, especially among African American and Hispanic individuals. Deep learning has been widely used to detect POAG using fundus images as its performance is comparable to or even surpasses diagnosis by clinicians. However, human bias in clinical diagnosis may be reflected and amplified in the widely-used deep learning models, thus impacting their performance. Biases may cause (1) underdiagnosis, increasing the risks of delayed or inadequate treatment, and (2) overdiagnosis, which may increase individuals' stress, fear, well-being, and unnecessary/costly treatment. In this study, we examined the underdiagnosis and overdiagnosis when applying deep learning in POAG detection based on the Ocular Hypertension Treatment Study (OHTS) from 22 centers across 16 states in the United States. Our results show that the widely-used deep learning model can underdiagnose or overdiagnose under-served populations. The most underdiagnosed group is female younger (< 60 yrs) group, and the most overdiagnosed group is Black older (≥ 60 yrs) group. Biased diagnosis through traditional deep learning methods may delay disease detection, treatment and create burdens among under-served populations, thereby, raising ethical concerns about using deep learning models in ophthalmology clinics.

Enhancing thoracic disease detection using chest X-rays from PubMed Central Open Access.

Large chest X-rays (CXR) datasets have been collected to train deep learning models to detect thorax pathology on CXR. However, most CXR datasets are from single-center studies and the collected pathologies are often imbalanced. The aim of this study was to automatically construct a public, weakly-labeled CXR database from articles in PubMed Central Open Access (PMC-OA) and to assess model performance on CXR pathology classification by using this database as additional training data. Our framework includes text extraction, CXR pathology verification, subfigure separation, and image modality classification. We have extensively validated the utility of the automatically generated image database on thoracic disease detection tasks, including Hernia, Lung Lesion, Pneumonia, and pneumothorax. We pick these diseases due to their historically poor performance in existing datasets: the NIH-CXR dataset (112,120 CXR) and the MIMIC-CXR dataset (243,324 CXR). We find that classifiers fine-tuned with additional PMC-CXR extracted by the proposed framework consistently and significantly achieved better performance than those without (e.g., Hernia: 0.9335 vs 0.9154; Lung Lesion: 0.7394 vs. 0.7207; Pneumonia: 0.7074 vs. 0.6709; Pneumothorax 0.8185 vs. 0.7517, all in AUC with p< 0.0001) for CXR pathology detection. In contrast to previous approaches that manually submit the medical images to the repository, our framework can automatically collect figures and their accompanied figure legends. Compared to previous studies, the proposed framework improved subfigure segmentation and incorporates our advanced self-developed NLP technique for CXR pathology verification. We hope it complements existing resources and improves our ability to make biomedical image data findable, accessible, interoperable, and reusable.

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.

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.

Automated diagnosing primary open-angle glaucoma from fundus image by simulating human's grading with deep learning.

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide. Although deep learning methods have been proposed to diagnose POAG, it remains challenging to develop a robust and explainable algorithm to automatically facilitate the downstream diagnostic tasks. In this study, we present an automated classification algorithm, GlaucomaNet, to identify POAG using variable fundus photographs from different populations and settings. GlaucomaNet consists of two convolutional neural networks to simulate the human grading process: learning the discriminative features and fusing the features for grading. We evaluated GlaucomaNet on two datasets: Ocular Hypertension Treatment Study (OHTS) participants and the Large-scale Attention-based Glaucoma (LAG) dataset. GlaucomaNet achieved the highest AUC of 0.904 and 0.997 for POAG diagnosis on OHTS and LAG datasets. An ensemble of network architectures further improved diagnostic accuracy. By simulating the human grading process, GlaucomaNet demonstrated high accuracy with increased transparency in POAG diagnosis (comprehensiveness scores of 97% and 36%). These methods also address two well-known challenges in the field: the need for increased image data diversity and relying heavily on perimetry for POAG diagnosis. These results highlight the potential of deep learning to assist and enhance clinical POAG diagnosis. GlaucomaNet is publicly available on https://github.com/bionlplab/GlaucomaNet .

Prediction With Unpredictable Feature Evolution.

Learning with feature evolution studies the scenario where the features of the data streams can evolve, i.e., old features vanish and new features emerge. Its goal is to keep the model always performing well even when the features happen to evolve. To tackle this problem, canonical methods assume that the old features will vanish simultaneously and the new features themselves will emerge simultaneously as well. They also assume that there is an overlapping period where old and new features both exist when the feature space starts to change. However, in reality, the feature evolution could be unpredictable, which means that the features can vanish or emerge arbitrarily, causing the overlapping period incomplete. In this article, we propose a novel paradigm: prediction with unpredictable feature evolution (PUFE) where the feature evolution is unpredictable. To address this problem, we fill the incomplete overlapping period and formulate it as a new matrix completion problem. We give a theoretical bound on the least number of observed entries to make the overlapping period intact. With this intact overlapping period, we leverage an ensemble method to take the advantage of both the old and new feature spaces without manually deciding which base models should be incorporated. Theoretical and experimental results validate that our method can always follow the best base models and, thus, realize the goal of learning with feature evolution.

Learning With Interpretable Structure From Gated RNN.

The interpretability of deep learning models has raised extended attention these years. It will be beneficial if we can learn an interpretable structure from deep learning models. In this article, we focus on recurrent neural networks (RNNs), especially gated RNNs whose inner mechanism is still not clearly understood. We find that finite-state automaton (FSA) that processes sequential data have a more interpretable inner mechanism according to the definition of interpretability and can be learned from RNNs as the interpretable structure. We propose two methods to learn FSA from RNN based on two different clustering methods. With the learned FSA and via experiments on artificial and real data sets, we find that FSA is more trustable than the RNN from which it learned, which gives FSA a chance to substitute RNNs in applications involving humans' lives or dangerous facilities. Besides, we analyze how the number of gates affects the performance of RNN. Our result suggests that gate in RNN is important but the less the better, which could be a guidance to design other RNNs. Finally, we observe that the FSA learned from RNN gives semantic aggregated states, and its transition graph shows us a very interesting vision of how RNNs intrinsically handle text classification tasks.