Browsing by Author "Hao, Xiaoke"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Diagnosis-guided method for identifying multi-modality neuroimaging biomarkers associated with genetic risk factors in Alzheimer’s disease
    (eProceedings, 2016) Hao, Xiaoke; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L.; Saykin, Andrew J.; Zhang, Daoqiang; Shen, Li; Department of Radiology and Imaging Sciences, IU School of Medicine
    Many recent imaging genetic studies focus on detecting the associations between genetic markers such as single nucleotide polymorphisms (SNPs) and quantitative traits (QTs). Although there exist a large number of generalized multivariate regression analysis methods, few of them have used diagnosis information in subjects to enhance the analysis performance. In addition, few of models have investigated the identification of multi-modality phenotypic patterns associated with interesting genotype groups in traditional methods. To reveal disease-relevant imaging genetic associations, we propose a novel diagnosis-guided multi-modality (DGMM) framework to discover multi-modality imaging QTs that are associated with both Alzheimer's disease (AD) and its top genetic risk factor (i.e., APOE SNP rs429358). The strength of our proposed method is that it explicitly models the priori diagnosis information among subjects in the objective function for selecting the disease-relevant and robust multi-modality QTs associated with the SNP. We evaluate our method on two modalities of imaging phenotypes, i.e., those extracted from structural magnetic resonance imaging (MRI) data and fluorodeoxyglucose positron emission tomography (FDG-PET) data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results demonstrate that our proposed method not only achieves better performances under the metrics of root mean squared error and correlation coefficient but also can identify common informative regions of interests (ROIs) across multiple modalities to guide the disease-induced biological interpretation, compared with other reference methods.
  • Thumbnail Image
    Item
    Identification of associations between genotypes and longitudinal phenotypes via temporally-constrained group sparse canonical correlation analysis
    (Oxford, 2017-07) Hao, Xiaoke; Li, Chanxiu; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L.; Saykin, Andrew J.; Shen, Li; Zhang, Daoqiang; Radiology and Imaging Sciences, School of Medicine
    Motivation: Neuroimaging genetics identifies the relationships between genetic variants (i.e., the single nucleotide polymorphisms) and brain imaging data to reveal the associations from genotypes to phenotypes. So far, most existing machine-learning approaches are widely used to detect the effective associations between genetic variants and brain imaging data at one time-point. However, those associations are based on static phenotypes and ignore the temporal dynamics of the phenotypical changes. The phenotypes across multiple time-points may exhibit temporal patterns that can be used to facilitate the understanding of the degenerative process. In this article, we propose a novel temporally constrained group sparse canonical correlation analysis (TGSCCA) framework to identify genetic associations with longitudinal phenotypic markers. Results: The proposed TGSCCA method is able to capture the temporal changes in brain from longitudinal phenotypes by incorporating the fused penalty, which requires that the differences between two consecutive canonical weight vectors from adjacent time-points should be small. A new efficient optimization algorithm is designed to solve the objective function. Furthermore, we demonstrate the effectiveness of our algorithm on both synthetic and real data (i.e., the Alzheimer’s Disease Neuroimaging Initiative cohort, including progressive mild cognitive impairment, stable MCI and Normal Control participants). In comparison with conventional SCCA, our proposed method can achieve strong associations and discover phenotypic biomarkers across multiple time-points to guide disease-progressive interpretation.
  • Thumbnail Image
    Item
    Identifying Candidate Genetic Associations with MRI-Derived AD-Related ROI via Tree-Guided Sparse Learning
    (IEEE, 2019-11) Hao, Xiaoke; Yao, Xiaohui; Risacher, Shannon L.; Saykin, Andrew J.; Yu, Jintai; Wang, Huifu; Tan, Lan; Shen, Li; Zhang, Daoqiang; Radiology and Imaging Sciences, School of Medicine
    Imaging genetics has attracted significant interests in recent studies. Traditional work has focused on mass-univariate statistical approaches that identify important single nucleotide polymorphisms (SNPs) associated with quantitative traits (QTs) of brain structure or function. More recently, to address the problem of multiple comparison and weak detection, multivariate analysis methods such as the least absolute shrinkage and selection operator (Lasso) are often used to select the most relevant SNPs associated with QTs. However, one problem of Lasso, as well as many other feature selection methods for imaging genetics, is that some useful prior information, e.g., the hierarchical structure among SNPs, are rarely used for designing a more powerful model. In this paper, we propose to identify the associations between candidate genetic features (i.e., SNPs) and magnetic resonance imaging (MRI)-derived measures using a tree-guided sparse learning (TGSL) method. The advantage of our method is that it explicitly models the complex hierarchical structure among the SNPs in the objective function for feature selection. Specifically, motivated by the biological knowledge, the hierarchical structures involving gene groups and linkage disequilibrium (LD) blocks as well as individual SNPs are imposed as a tree-guided regularization term in our TGSL model. Experimental studies on simulation data and the Alzheimer's Disease Neuroimaging Initiative (ADNI) data show that our method not only achieves better predictions than competing methods on the MRI-derived measures of AD-related region of interests (ROIs) (i.e., hippocampus, parahippocampal gyrus, and precuneus), but also identifies sparse SNP patterns at the block level to better guide the biological interpretation.
  • Thumbnail Image
    Item
    Identifying Multimodal Intermediate Phenotypes between Genetic Risk Factors and Disease Status in Alzheimer’s Disease
    (Springer, 2016-10) Hao, Xiaoke; Yao, Xiaohui; Yan, Jingwen; Risacher, Shannon L.; Saykin, Andrew J.; Zhang, Daoqiang; Shen, Li; Radiology and Imaging Sciences, School of Medicine
    Neuroimaging genetics has attracted growing attention and interest, which is thought to be a powerful strategy to examine the influence of genetic variants (i.e., single nucleotide polymorphisms (SNPs)) on structures or functions of human brain. In recent studies, univariate or multivariate regression analysis methods are typically used to capture the effective associations between genetic variants and quantitative traits (QTs) such as brain imaging phenotypes. The identified imaging QTs, although associated with certain genetic markers, may not be all disease specific. A useful, but underexplored, scenario could be to discover only those QTs associated with both genetic markers and disease status for revealing the chain from genotype to phenotype to symptom. In addition, multimodal brain imaging phenotypes are extracted from different perspectives and imaging markers consistently showing up in multimodalities may provide more insights for mechanistic understanding of diseases (i.e., Alzheimer’s disease (AD)). In this work, we propose a general framework to exploit multi-modal brain imaging phenotypes as intermediate traits that bridge genetic risk factors and multi-class disease status. We applied our proposed method to explore the relation between the well-known AD risk SNP APOE rs429358 and three baseline brain imaging modalities (i.e., structural magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET) and F-18 florbetapir PET scans amyloid imaging (AV45)) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The empirical results demonstrate that our proposed method not only helps improve the performances of imaging genetic associations, but also discovers robust and consistent regions of interests (ROIs) across multi-modalities to guide the disease-induced interpretation.
  • Thumbnail Image
    Item
    Mining Outcome-relevant Brain Imaging Genetic Associations via Three-way Sparse Canonical Correlation Analysis in Alzheimer’s Disease
    (SpringerNature, 2017-03-14) Hao, Xiaoke; Liu, Chanxiu; Du, Lei; Yao, Xiaohui; Yan, Jingwen; Risacher, Shannon L.; Saykin, Andrew J.; Shen, Li; Zhang, Daoqiang; Department of Radiology and Imaging Sciences, IU School of Medicine
    Neuroimaging genetics is an emerging field that aims to identify the associations between genetic variants (e.g., single nucleotide polymorphisms (SNPs)) and quantitative traits (QTs) such as brain imaging phenotypes. In recent studies, in order to detect complex multi-SNP-multi-QT associations, bi-multivariate techniques such as various structured sparse canonical correlation analysis (SCCA) algorithms have been proposed and used in imaging genetics studies. However, associations between genetic markers and imaging QTs identified by existing bi-multivariate methods may not be all disease specific. To bridge this gap, we propose an analytical framework, based on three-way sparse canonical correlation analysis (T-SCCA), to explore the intrinsic associations among genetic markers, imaging QTs, and clinical scores of interest. We perform an empirical study using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort to discover the relationships among SNPs from AD risk gene APOE, imaging QTs extracted from structural magnetic resonance imaging scans, and cognitive and diagnostic outcomes. The proposed T-SCCA model not only outperforms the traditional SCCA method in terms of identifying strong associations, but also discovers robust outcome-relevant imaging genetic patterns, demonstrating its promise for improving disease-related mechanistic understanding.
  • Thumbnail Image
    Item
    Multi-modal Neuroimaging Feature Selection with Consistent Metric Constraint for Diagnosis of Alzheimer’s Disease
    (Elsevier, 2020-02) Hao, Xiaoke; Bao, Yongjin; Guo, Yingchun; Yu, Ming; Zhang, Daoqiang; Risacher, Shannon L.; Saykin, Andrew J.; Yao, Xiaohui; Shen, Li; Radiology and Imaging Sciences, School of Medicine
    The accurate diagnosis of Alzheimer's disease (AD) and its early stage, e.g., mild cognitive impairment (MCI), is essential for timely treatment or possible intervention to slow down AD progression. Recent studies have demonstrated that multiple neuroimaging and biological measures contain complementary information for diagnosis and prognosis. Therefore, information fusion strategies with multi-modal neuroimaging data, such as voxel-based measures extracted from structural MRI (VBM-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET), have shown their effectiveness for AD diagnosis. However, most existing methods are proposed to simply integrate the multi-modal data, but do not make full use of structure information across the different modalities. In this paper, we propose a novel multi-modal neuroimaging feature selection method with consistent metric constraint (MFCC) for AD analysis. First, the similarity is calculated for each modality (i.e. VBM-MRI or FDG-PET) individually by random forest strategy, which can extract pairwise similarity measures for multiple modalities. Then the group sparsity regularization term and the sample similarity constraint regularization term are used to constrain the objective function to conduct feature selection from multiple modalities. Finally, the multi-kernel support vector machine (MK-SVM) is used to fuse the features selected from different models for final classification. The experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) show that the proposed method has better classification performance than the start-of-the-art multimodality-based methods. Specifically, we achieved higher accuracy and area under the curve (AUC) for AD versus normal controls (NC), MCI versus NC, and MCI converters (MCI-C) versus MCI non-converters (MCI-NC) on ADNI datasets. Therefore, the proposed model not only outperforms the traditional method in terms of AD/MCI classification, but also discovers the characteristics associated with the disease, demonstrating its promise for improving disease-related mechanistic understanding.