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DIAGNOSIS STATUS GUIDED BRAIN IMAGING GENETICS VIA INTEGRATED REGRESSION AND SPARSE CANONICAL CORRELATION ANALYSIS.

ABSTRACT: Brain imaging genetics use the imaging quantitative traits (QTs) as intermediate endophenotypes to identify the genetic basis of the brain structure, function and abnormality. The regression and canonical correlation analysis (CCA) coupled with sparsity regularization are widely used in imaging genetics. The regression only selects relevant features for predictors. SCCA overcomes this but is unsupervised and thus could not make use of the diagnosis information. We propose a novel method integrating regression and SCCA together to construct a supervised sparse bi-multivariate learning model. The regression part plays a role of providing guidance for imaging QTs selection, and the SCCA part is focused on selecting relevant genetic markers and imaging QTs. We propose an efficient algorithm based on the alternative search method. Our method obtains better feature selection results than both regression and SCCA on both synthetic and real neuroimaging data. This demonstrates that our method is a promising bi-multivariate tool for brain imaging genetics.

SUBMITTER: Du L

PROVIDER: S-EPMC6914314 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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DIAGNOSIS STATUS GUIDED BRAIN IMAGING GENETICS VIA INTEGRATED REGRESSION AND SPARSE CANONICAL CORRELATION ANALYSIS.

Du Lei L Liu Kefei K Yao Xiaohui X Risacher Shannon L SL Guo Lei L Saykin Andrew J AJ Shen Li L

Proceedings. IEEE International Symposium on Biomedical Imaging 20190401

Brain imaging genetics use the imaging quantitative traits (QTs) as intermediate endophenotypes to identify the genetic basis of the brain structure, function and abnormality. The regression and canonical correlation analysis (CCA) coupled with sparsity regularization are widely used in imaging genetics. The regression only selects relevant features for predictors. SCCA overcomes this but is unsupervised and thus could not make use of the diagnosis information. We propose a novel method integrat ...[more]

PMID: 31844486

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Project description:MotivationRecent advances in technology for brain imaging and high-throughput genotyping have motivated studies examining the influence of genetic variation on brain structure. Wang et al. have developed an approach for the analysis of imaging genomic studies using penalized multi-task regression with regularization based on a novel group l2,1-norm penalty which encourages structured sparsity at both the gene level and SNP level. While incorporating a number of useful features, the proposed method only furnishes a point estimate of the regression coefficients; techniques for conducting statistical inference are not provided. A new Bayesian method is proposed here to overcome this limitation.ResultsWe develop a Bayesian hierarchical modeling formulation where the posterior mode corresponds to the estimator proposed by Wang et al. and an approach that allows for full posterior inference including the construction of interval estimates for the regression parameters. We show that the proposed hierarchical model can be expressed as a three-level Gaussian scale mixture and this representation facilitates the use of a Gibbs sampling algorithm for posterior simulation. Simulation studies demonstrate that the interval estimates obtained using our approach achieve adequate coverage probabilities that outperform those obtained from the nonparametric bootstrap. Our proposed methodology is applied to the analysis of neuroimaging and genetic data collected as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI), and this analysis of the ADNI cohort demonstrates clearly the value added of incorporating interval estimation beyond only point estimation when relating SNPs to brain imaging endophenotypes.Availability and implementationSoftware and sample data is available as an R package 'bgsmtr' that can be downloaded from The Comprehensive R Archive Network (CRAN).Contactnathoo@uvic.ca.Supplementary informationSupplementary data are available at Bioinformatics online.

Project description:Brain imaging genetics can demonstrate the complicated relationship between genetic factors and the structure or function of the humankind brain. Therefore, it has become an important research topic and attracted more and more attention from scholars. The structured sparse canonical correlation analysis (SCCA) model has been widely used to identify the association between brain image data and genetic data in imaging genetics. To investigate the intricate genetic basis of cerebrum imaging phenotypes, a great deal of other standard SCCA methods combining different interested structed have now appeared. For example, some models use group lasso penalty, and some use the fused lasso or the graph/network guided fused lasso for feature selection. However, prior knowledge may not be completely available and the group lasso methods have limited capabilities in practical applications. The graph/network guided approaches can use sample correlation to define constraints, thereby overcoming this problem. Unfortunately, this also has certain limitations. The graph/network conducted methods are susceptible to the sign of the sample correlation of the data, which will affect the stability of the model. To improve the efficiency and stability of SCCA, a sparse canonical correlation analysis model with GraphNet regularization (FGLGNSCCA) is proposed in this manuscript. Based on the FGLSCCA model, the GraphNet regularization penalty is imposed in our study and an optimization algorithm is presented to optimize the model. The structural Magnetic Resonance Imaging (sMRI) and gene expression data are used in this study to find the genotype and characteristics of brain regions associated with Alzheimer's disease (AD). Experiment results shown that the new FGLGNSCCA model proposed in this manuscript is superior or equivalent to traditional methods in both artificially synthesized neuroimaging genetics data or actual neuroimaging genetics data. It can select essential features more powerfully compared with other multivariate methods and identify significant canonical correlation coefficients as well as captures more significant typical weight patterns which demonstrated its excellent ability in finding biologically important imaging genetic relations.

Dataset Information

DIAGNOSIS STATUS GUIDED BRAIN IMAGING GENETICS VIA INTEGRATED REGRESSION AND SPARSE CANONICAL CORRELATION ANALYSIS.

Publications

DIAGNOSIS STATUS GUIDED BRAIN IMAGING GENETICS VIA INTEGRATED REGRESSION AND SPARSE CANONICAL CORRELATION ANALYSIS.

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