Network-guided sparse learning for predicting cognitive outcomes from MRI measures

Alzheimer's disease (AD) is characterized by gradual neurodegeneration and loss of brain function, especially for memory during early stages. Regression analysis has been widely applied to AD research to relate clinical and biomarker data such as predicting cognitive outcomes from MRI measures. In particular, sparse models have been proposed to identify the optimal imaging markers with high prediction power. However, the complex relationship among imaging markers are often overlooked or simplified in the existing methods. To address this issue, we present a new sparse learning method by introducing a novel network term to more flexibly model the relationship among imaging markers. The proposed algorithm is applied to the ADNI study for predicting cognitive outcomes using MRI scans. The effectiveness of our method is demonstrated by its improved prediction performance over several state-of-the-art competing methods and accurate identification of cognition-relevant imaging markers that are biologically meaningful

Identifying progressive imaging genetic patterns via multi-task sparse canonical correlation analysis: a longitudinal study of the ADNI cohort

Motivation Identifying the genetic basis of the brain structure, function and disorder by using the imaging quantitative traits (QTs) as endophenotypes is an important task in brain science. Brain QTs often change over time while the disorder progresses and thus understanding how the genetic factors play roles on the progressive brain QT changes is of great importance and meaning. Most existing imaging genetics methods only analyze the baseline neuroimaging data, and thus those longitudinal imaging data across multiple time points containing important disease progression information are omitted. Results We propose a novel temporal imaging genetic model which performs the multi-task sparse canonical correlation analysis (T-MTSCCA). Our model uses longitudinal neuroimaging data to uncover that how single nucleotide polymorphisms (SNPs) play roles on affecting brain QTs over the time. Incorporating the relationship of the longitudinal imaging data and that within SNPs, T-MTSCCA could identify a trajectory of progressive imaging genetic patterns over the time. We propose an efficient algorithm to solve the problem and show its convergence. We evaluate T-MTSCCA on 408 subjects from the Alzheimer’s Disease Neuroimaging Initiative database with longitudinal magnetic resonance imaging data and genetic data available. The experimental results show that T-MTSCCA performs either better than or equally to the state-of-the-art methods. In particular, T-MTSCCA could identify higher canonical correlation coefficients and capture clearer canonical weight patterns. This suggests that T-MTSCCA identifies time-consistent and time-dependent SNPs and imaging QTs, which further help understand the genetic basis of the brain QT changes over the time during the disease progression. Availability and implementation The software and simulation data are publicly available at https://github.com/dulei323/TMTSCCA. Supplementary information Supplementary data are available at Bioinformatics online

Identifying the neuroanatomical basis of cognitive impairment in Alzheimer's disease by correlation- and nonlinearity-aware sparse Bayesian learning

Predicting cognitive performance of subjects from their magnetic resonance imaging (MRI) measures and identifying relevant imaging biomarkers are important research topics in the study of Alzheimer's disease. Traditionally, this task is performed by formulating a linear regression problem. Recently, it is found that using a linear sparse regression model can achieve better prediction accuracy. However, most existing studies only focus on the exploitation of sparsity of regression coefficients, ignoring useful structure information in regression coefficients. Also, these linear sparse models may not capture more complicated and possibly nonlinear relationships between cognitive performance and MRI measures. Motivated by these observations, in this work we build a sparse multivariate regression model for this task and propose an empirical sparse Bayesian learning algorithm. Different from existing sparse algorithms, the proposed algorithm models the response as a nonlinear function of the predictors by extending the predictor matrix with block structures. Further, it exploits not only inter-vector correlation among regression coefficient vectors, but also intra-block correlation in each regression coefficient vector. Experiments on the Alzheimer's Disease Neuroimaging Initiative database showed that the proposed algorithm not only achieved better prediction performance than state-of-the-art competitive methods, but also effectively identified biologically meaningful patterns

Association between structural connectivity and generalized cognitive spectrum in alzheimer’s disease

Modeling disease progression through the cognitive scores has become an attractive challenge in the field of computational neuroscience due to its importance for early diagnosis of Alzheimer’s disease (AD). Several scores such as Alzheimer’s Disease Assessment Scale cognitive total score, Mini Mental State Exam score and Rey Auditory Verbal Learning Test provide a quantitative assessment of the cognitive conditions of the patients and are commonly used as objective criteria for clinical diagnosis of dementia and mild cognitive impairment (MCI). On the other hand, connectivity patterns extracted from diffusion tensor imaging (DTI) have been successfully used to classify AD and MCI subjects with machine learning algorithms proving their potential application in the clinical setting. In this work, we carried out a pilot study to investigate the strength of association between DTI structural connectivity of a mixed ADNI cohort and cognitive spectrum in AD. We developed a machine learning framework to find a generalized cognitive score that summarizes the different functional domains reflected by each cognitive clinical index and to identify the connectivity biomarkers more significantly associated with the score. The results indicate that the efficiency and the centrality of some regions can effectively track cognitive impairment in AD showing a significant correlation with the generalized cognitive score (R = 0.7)

Deep sparse multi-task learning for feature selection in Alzheimer’s disease diagnosis

Recently, neuroimaging-based Alzheimer’s disease (AD) or mild cognitive impairment (MCI) diagnosis has attracted researchers in the field, due to the increasing prevalence of the diseases. Unfortunately, the unfavorable high-dimensional nature of neuroimaging data, but a limited small number of samples available, makes it challenging to build a robust computer-aided diagnosis system. Machine learning techniques have been considered as a useful tool in this respect and, among various methods, sparse regression has shown its validity in the literature. However, to our best knowledge, the existing sparse regression methods mostly try to select features based on the optimal regression coefficients in one step. We argue that since the training feature vectors are composed of both informative and uninformative or less informative features, the resulting optimal regression coefficients are inevidently affected by the uninformative or less informative features. To this end, we first propose a novel deep architecture to recursively discard uninformative features by performing sparse multi-task learning in a hierarchical fashion. We further hypothesize that the optimal regression coefficients reflect the relative importance of features in representing the target response variables. In this regard, we use the optimal regression co-efficients learned in one hierarchy as feature weighting factors in the following hierarchy, and formulate a weighted sparse multi-task learning method. Lastly, we also take into account the distributional characteristics of samples per class and use clustering-induced subclass label vectors as target response values in our sparse regression model. In our experiments on the ADNI cohort, we performed both binary and multi-class classification tasks in AD/MCI diagnosis and showed the superiority of the proposed method by comparing with the state-of-the-art methods

Identifying disease sensitive and quantitative trait-relevant biomarkers from multidimensional heterogeneous imaging genetics data via sparse multimodal multitask learning

Motivation: Recent advances in brain imaging and high-throughput genotyping techniques enable new approaches to study the influence of genetic and anatomical variations on brain functions and disorders. Traditional association studies typically perform independent and pairwise analysis among neuroimaging measures, cognitive scores and disease status, and ignore the important underlying interacting relationships between these units

Structured Sparse Methods for Imaging Genetics

abstract: Imaging genetics is an emerging and promising technique that investigates how genetic variations affect brain development, structure, and function. By exploiting disorder-related neuroimaging phenotypes, this class of studies provides a novel direction to reveal and understand the complex genetic mechanisms. Oftentimes, imaging genetics studies are challenging due to the relatively small number of subjects but extremely high-dimensionality of both imaging data and genomic data. In this dissertation, I carry on my research on imaging genetics with particular focuses on two tasks---building predictive models between neuroimaging data and genomic data, and identifying disorder-related genetic risk factors through image-based biomarkers. To this end, I consider a suite of structured sparse methods---that can produce interpretable models and are robust to overfitting---for imaging genetics. With carefully-designed sparse-inducing regularizers, different biological priors are incorporated into learning models. More specifically, in the Allen brain image--gene expression study, I adopt an advanced sparse coding approach for image feature extraction and employ a multi-task learning approach for multi-class annotation. Moreover, I propose a label structured-based two-stage learning framework, which utilizes the hierarchical structure among labels, for multi-label annotation. In the Alzheimer's disease neuroimaging initiative (ADNI) imaging genetics study, I employ Lasso together with EDPP (enhanced dual polytope projections) screening rules to fast identify Alzheimer's disease risk SNPs. I also adopt the tree-structured group Lasso with MLFre (multi-layer feature reduction) screening rules to incorporate linkage disequilibrium information into modeling. Moreover, I propose a novel absolute fused Lasso model for ADNI imaging genetics. This method utilizes SNP spatial structure and is robust to the choice of reference alleles of genotype coding. In addition, I propose a two-level structured sparse model that incorporates gene-level networks through a graph penalty into SNP-level model construction. Lastly, I explore a convolutional neural network approach for accurate predicting Alzheimer's disease related imaging phenotypes. Experimental results on real-world imaging genetics applications demonstrate the efficiency and effectiveness of the proposed structured sparse methods.Dissertation/ThesisDoctoral Dissertation Computer Science 201