Jiguo Cao

Ghazal Mirabnahrazam, Da Ma, Cédric Beaulac et al.

Dementia of Alzheimer's Type (DAT) is a complex disorder influenced by numerous factors, but it is unclear how each factor contributes to disease progression. An in-depth examination of these factors may yield an accurate estimate of time-to-conversion to DAT for patients at various disease stages. We used 401 subjects with 63 features from MRI, genetic, and CDC (Cognitive tests, Demographic, and CSF) data modalities in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We used a deep learning-based survival analysis model that extends the classic Cox regression model to predict time-to-conversion to DAT. Our findings showed that genetic features contributed the least to survival analysis, while CDC features contributed the most. Combining MRI and genetic features improved survival prediction over using either modality alone, but adding CDC to any combination of features only worked as well as using only CDC features. Consequently, our study demonstrated that using the current clinical procedure, which includes gathering cognitive test results, can outperform survival analysis results produced using costly genetic or CSF data.

Ghazal Mirabnahrazam, Da Ma, Sieun Lee et al.

Background: The increasing availability of databases containing both magnetic resonance imaging (MRI) and genetic data allows researchers to utilize multimodal data to better understand the characteristics of dementia of Alzheimer's type (DAT). Objective: The goal of this study was to develop and analyze novel biomarkers that can help predict the development and progression of DAT. Methods: We used feature selection and ensemble learning classifier to develop an image/genotype-based DAT score that represents a subject's likelihood of developing DAT in the future. Three feature types were used: MRI only, genetic only, and combined multimodal data. We used a novel data stratification method to better represent different stages of DAT. Using a pre-defined 0.5 threshold on DAT scores, we predicted whether or not a subject would develop DAT in the future. Results: Our results on Alzheimer's Disease Neuroimaging Initiative (ADNI) database showed that dementia scores using genetic data could better predict future DAT progression for currently normal control subjects (Accuracy=0.857) compared to MRI (Accuracy=0.143), while MRI can better characterize subjects with stable mild cognitive impairment (Accuracy=0.614) compared to genetics (Accuracy=0.356). Combining MRI and genetic data showed improved classification performance in the remaining stratified groups. Conclusion: MRI and genetic data can contribute to DAT prediction in different ways. MRI data reflects anatomical changes in the brain, while genetic data can detect the risk of DAT progression prior to the symptomatic onset. Combining information from multimodal data in the right way can improve prediction performance.

Sidi Wu, Cédric Beaulac, Jiguo Cao

The regression of a functional response on a set of scalar predictors can be a challenging task, especially if there is a large number of predictors, or the relationship between those predictors and the response is nonlinear. In this work, we propose a solution to this problem: a feed-forward neural network (NN) designed to predict a functional response using scalar inputs. First, we transform the functional response to a finite-dimensional representation and construct an NN that outputs this representation. Then, we propose to modify the output of an NN via the objective function and introduce different objective functions for network training. The proposed models are suited for both regularly and irregularly spaced data, and a roughness penalty can be further applied to control the smoothness of the predicted curve. The difficulty in implementing both those features lies in the definition of objective functions that can be back-propagated. In our experiments, we demonstrate that our model outperforms the conventional function-on-scalar regression model in multiple scenarios while computationally scaling better with the dimension of the predictors.

Cédric Beaulac, Sidi Wu, Erin Gibson et al.

A major issue in the association of genes to neuroimaging phenotypes is the high dimension of both genetic data and neuroimaging data. In this article, we tackle the latter problem with an eye toward developing solutions that are relevant for disease prediction. Supported by a vast literature on the predictive power of neural networks, our proposed solution uses neural networks to extract from neuroimaging data features that are relevant for predicting Alzheimer's Disease (AD) for subsequent relation to genetics. Our neuroimaging-genetic pipeline is comprised of image processing, neuroimaging feature extraction and genetic association steps. We propose a neural network classifier for extracting neuroimaging features that are related with disease and a multivariate Bayesian group sparse regression model for genetic association. We compare the predictive power of these features to expert selected features and take a closer look at the SNPs identified with the new neuroimaging features.

Haixu Wang, Jiguo Cao

Using representations of functional data can be more convenient and beneficial in subsequent statistical models than direct observations. These representations, in a lower-dimensional space, extract and compress information from individual curves. The existing representation learning approaches in functional data analysis usually use linear mapping in parallel to those from multivariate analysis, e.g., functional principal component analysis (FPCA). However, functions, as infinite-dimensional objects, sometimes have nonlinear structures that cannot be uncovered by linear mapping. Linear methods will be more overwhelmed given multivariate functional data. For that matter, this paper proposes a functional nonlinear learning (FunNoL) method to sufficiently represent multivariate functional data in a lower-dimensional feature space. Furthermore, we merge a classification model for enriching the ability of representations in predicting curve labels. Hence, representations from FunNoL can be used for both curve reconstruction and classification. Additionally, we have endowed the proposed model with the ability to address the missing observation problem as well as to further denoise observations. The resulting representations are robust to observations that are locally disturbed by uncontrollable random noises. We apply the proposed FunNoL method to several real data sets and show that FunNoL can achieve better classifications than FPCA, especially in the multivariate functional data setting. Simulation studies have shown that FunNoL provides satisfactory curve classification and reconstruction regardless of data sparsity.

Siying Ma, Mehrdad M. Zadeh, Mauricio Soroco et al.

Recent advances in scientific machine learning (SciML) have enabled neural operators (NOs) to serve as powerful surrogates for modeling the dynamic evolution of physical systems governed by partial differential equations (PDEs). While existing approaches focus primarily on learning simulations from the target PDE, they often overlook more fundamental physical principles underlying these equations. Inspired by how numerical solvers are compatible with simulations of different settings of PDEs, we propose a multiphysics training framework that jointly learns from both the original PDEs and their simplified basic forms. Our framework enhances data efficiency, reduces predictive errors, and improves out-of-distribution (OOD) generalization, particularly in scenarios involving shifts of physical parameters and synthetic-to-real transfer. Our method is architecture-agnostic and demonstrates consistent improvements in normalized root mean square error (nRMSE) across a wide range of 1D/2D/3D PDE problems. Through extensive experiments, we show that explicit incorporation of fundamental physics knowledge significantly strengthens the generalization ability of neural operators. We will release models and codes at https://sites.google.com/view/sciml-fundemental-pde.

Sidi Wu, Cédric Beaulac, Jiguo Cao

A common pipeline in functional data analysis is to first convert the discretely observed data to smooth functions, and then represent the functions by a finite-dimensional vector of coefficients summarizing the information. Existing methods for data smoothing and dimensional reduction mainly focus on learning the linear mappings from the data space to the representation space, however, learning only the linear representations may not be sufficient. In this study, we propose to learn the nonlinear representations of functional data using neural network autoencoders designed to process data in the form it is usually collected without the need of preprocessing. We design the encoder to employ a projection layer computing the weighted inner product of the functional data and functional weights over the observed timestamp, and the decoder to apply a recovery layer that maps the finite-dimensional vector extracted from the functional data back to functional space using a set of predetermined basis functions. The developed architecture can accommodate both regularly and irregularly spaced data. Our experiments demonstrate that the proposed method outperforms functional principal component analysis in terms of prediction and classification, and maintains superior smoothing ability and better computational efficiency in comparison to the conventional autoencoders under both linear and nonlinear settings.

Haixu Wang, Jiguo Cao, Jian Pei

This study presents a novel representation learning model tailored for dynamic networks, which describes the continuously evolving relationships among individuals within a population. The problem is encapsulated in the dimension reduction topic of functional data analysis. With dynamic networks represented as matrix-valued functions, our objective is to map this functional data into a set of vector-valued functions in a lower-dimensional learning space. This space, defined as a metric functional space, allows for the calculation of norms and inner products. By constructing this learning space, we address (i) attribute learning, (ii) community detection, and (iii) link prediction and recovery of individual nodes in the dynamic network. Our model also accommodates asymmetric low-dimensional representations, enabling the separate study of nodes' regulatory and receiving roles. Crucially, the learning method accounts for the time-dependency of networks, ensuring that representations are continuous over time. The functional learning space we define naturally spans the time frame of the dynamic networks, facilitating both the inference of network links at specific time points and the reconstruction of the entire network structure without direct observation. We validated our approach through simulation studies and real-world applications. In simulations, we compared our methods link prediction performance to existing approaches under various data corruption scenarios. For real-world applications, we examined a dynamic social network replicated across six ant populations, demonstrating that our low-dimensional learning space effectively captures interactions, roles of individual ants, and the social evolution of the network. Our findings align with existing knowledge of ant colony behavior.

Bingfan Liu, Haolun Shi, Jiguo Cao

Survival analysis utilizing multiple longitudinal medical images plays a pivotal role in the early detection and prognosis of diseases by providing insight beyond single-image evaluations. However, current methodologies often inadequately utilize censored data, overlook correlations among longitudinal images measured over multiple time points, and lack interpretability. We introduce SurLonFormer, a novel Transformer-based neural network that integrates longitudinal medical imaging with structured data for survival prediction. Our architecture comprises three key components: a Vision Encoder for extracting spatial features, a Sequence Encoder for aggregating temporal information, and a Survival Encoder based on the Cox proportional hazards model. This framework effectively incorporates censored data, addresses scalability issues, and enhances interpretability through occlusion sensitivity analysis and dynamic survival prediction. Extensive simulations and a real-world application in Alzheimer's disease analysis demonstrate that SurLonFormer achieves superior predictive performance and successfully identifies disease-related imaging biomarkers.

Haixu Wang, Jiguo Cao

High-dimensional functional time series (HDFTS) are often characterized by nonlinear trends and high spatial dimensions. Such data poses unique challenges for modeling and forecasting due to the nonlinearity, nonstationarity, and high dimensionality. We propose a novel probabilistic functional neural network (ProFnet) to address these challenges. ProFnet integrates the strengths of feedforward and deep neural networks with probabilistic modeling. The model generates probabilistic forecasts using Monte Carlo sampling and also enables the quantification of uncertainty in predictions. While capturing both temporal and spatial dependencies across multiple regions, ProFnet offers a scalable and unified solution for large datasets. Applications to Japan's mortality rates demonstrate superior performance. This approach enhances predictive accuracy and provides interpretable uncertainty estimates, making it a valuable tool for forecasting complex high-dimensional functional data and HDFTS.

Barinder Thind, Kevin Multani, Jiguo Cao

In recent years, there has been considerable innovation in the world of predictive methodologies. This is evident by the relative domination of machine learning approaches in various classification competitions. While these algorithms have excelled at multivariate problems, they have remained dormant in the realm of functional data analysis. We extend notable deep learning methodologies to the domain of functional data for the purpose of classification problems. We highlight the effectiveness of our method in a number of classification applications such as classification of spectrographic data. Moreover, we demonstrate the performance of our classifier through simulation studies in which we compare our approach to the functional linear model and other conventional classification methods.

Barinder Thind, Sidi Wu, Richard Groenewald et al.

Neural networks have excelled at regression and classification problems when the input space consists of scalar variables. As a result of this proficiency, several popular packages have been developed that allow users to easily fit these kinds of models. However, the methodology has excluded the use of functional covariates and to date, there exists no software that allows users to build deep learning models with this generalized input space. To the best of our knowledge, the functional neural network (FuncNN) library is the first such package in any programming language; the library has been developed for R and is built on top of the keras architecture. Throughout this paper, several functions are introduced that provide users an avenue to easily build models, generate predictions, and run cross-validations. A summary of the underlying methodology is also presented. The ultimate contribution is a package that provides a set of general modelling and diagnostic tools for data problems in which there exist both functional and scalar covariates.

Barinder Thind, Kevin Multani, Jiguo Cao

We present a methodology for integrating functional data into deep densely connected feed-forward neural networks. The model is defined for scalar responses with multiple functional and scalar covariates. A by-product of the method is a set of dynamic functional weights that can be visualized during the optimization process. This visualization leads to greater interpretability of the relationship between the covariates and the response relative to conventional neural networks. The model is shown to perform well in a number of contexts including prediction of new data and recovery of the true underlying functional weights; these results were confirmed through real applications and simulation studies. A forthcoming R package is developed on top of a popular deep learning library (Keras) allowing for general use of the approach.

Nicole Croteau, Farouk S. Nathoo, Jiguo Cao et al.

Brain decoding involves the determination of a subject's cognitive state or an associated stimulus from functional neuroimaging data measuring brain activity. In this setting the cognitive state is typically characterized by an element of a finite set, and the neuroimaging data comprise voluminous amounts of spatiotemporal data measuring some aspect of the neural signal. The associated statistical problem is one of classification from high-dimensional data. We explore the use of functional principal component analysis, mutual information networks, and persistent homology for examining the data through exploratory analysis and for constructing features characterizing the neural signal for brain decoding. We review each approach from this perspective, and we incorporate the features into a classifier based on symmetric multinomial logistic regression with elastic net regularization. The approaches are illustrated in an application where the task is to infer, from brain activity measured with magnetoencephalography (MEG), the type of video stimulus shown to a subject.