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Transcriptome-guided amyloid imaging genetic analysis via a novel structured sparse learning algorithm.

ABSTRACT: MOTIVATION:Imaging genetics is an emerging field that studies the influence of genetic variation on brain structure and function. The major task is to examine the association between genetic markers such as single-nucleotide polymorphisms (SNPs) and quantitative traits (QTs) extracted from neuroimaging data. The complexity of these datasets has presented critical bioinformatics challenges that require new enabling tools. Sparse canonical correlation analysis (SCCA) is a bi-multivariate technique used in imaging genetics to identify complex multi-SNP-multi-QT associations. However, most of the existing SCCA algorithms are designed using the soft thresholding method, which assumes that the input features are independent from one another. This assumption clearly does not hold for the imaging genetic data. In this article, we propose a new knowledge-guided SCCA algorithm (KG-SCCA) to overcome this limitation as well as improve learning results by incorporating valuable prior knowledge. RESULTS:The proposed KG-SCCA method is able to model two types of prior knowledge: one as a group structure (e.g. linkage disequilibrium blocks among SNPs) and the other as a network structure (e.g. gene co-expression network among brain regions). The new model incorporates these prior structures by introducing new regularization terms to encourage weight similarity between grouped or connected features. A new algorithm is designed to solve the KG-SCCA model without imposing the independence constraint on the input features. We demonstrate the effectiveness of our algorithm with both synthetic and real data. For real data, using an Alzheimer's disease (AD) cohort, we examine the imaging genetic associations between all SNPs in the APOE gene (i.e. top AD gene) and amyloid deposition measures among cortical regions (i.e. a major AD hallmark). In comparison with a widely used SCCA implementation, our KG-SCCA algorithm produces not only improved cross-validation performances but also biologically meaningful results. AVAILABILITY:Software is freely available on request.

SUBMITTER: Yan J

PROVIDER: S-EPMC4147918 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Transcriptome-guided amyloid imaging genetic analysis via a novel structured sparse learning algorithm.

Yan Jingwen J Du Lei L Kim Sungeun S Risacher Shannon L SL Huang Heng H Moore Jason H JH Saykin Andrew J AJ Shen Li L

Bioinformatics (Oxford, England) 20140901 17

<h4>Motivation</h4>Imaging genetics is an emerging field that studies the influence of genetic variation on brain structure and function. The major task is to examine the association between genetic markers such as single-nucleotide polymorphisms (SNPs) and quantitative traits (QTs) extracted from neuroimaging data. The complexity of these datasets has presented critical bioinformatics challenges that require new enabling tools. Sparse canonical correlation analysis (SCCA) is a bi-multivariate t ...[more]

PMID: 25161248

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Project description:Oscillatory processes at all spatial scales and on all frequencies underpin brain function. Electrophysiological Source Imaging (ESI) is the data-driven brain imaging modality that provides the inverse solutions to the source processes of the EEG, MEG, or ECoG data. This study aimed to carry out an ESI of the source cross-spectrum while controlling common distortions of the estimates. As with all ESI-related problems under realistic settings, the main obstacle we faced is a severely ill-conditioned and high-dimensional inverse problem. Therefore, we opted for Bayesian inverse solutions that posited a priori probabilities on the source process. Indeed, rigorously specifying both the likelihoods and a priori probabilities of the problem leads to the proper Bayesian inverse problem of cross-spectral matrices. These inverse solutions are our formal definition for cross-spectral ESI (cESI), which requires a priori of the source cross-spectrum to counter the severe ill-condition and high-dimensionality of matrices. However, inverse solutions for this problem were NP-hard to tackle or approximated within iterations with bad-conditioned matrices in the standard ESI setup. We introduce cESI with a joint a priori probability upon the source cross-spectrum to avoid these problems. cESI inverse solutions are low-dimensional ones for the set of random vector instances and not random matrices. We achieved cESI inverse solutions through the variational approximations via our Spectral Structured Sparse Bayesian Learning (ssSBL) algorithm https://github.com/CCC-members/Spectral-Structured-Sparse-Bayesian-Learning. We compared low-density EEG (10-20 system) ssSBL inverse solutions with reference cESIs for two experiments: (a) high-density MEG that were used to simulate EEG and (b) high-density macaque ECoG that were recorded simultaneously with EEG. The ssSBL resulted in two orders of magnitude with less distortion than the state-of-the-art ESI methods. Our cESI toolbox, including the ssSBL method, is available at https://github.com/CCC-members/BC-VARETA_Toolbox.

Dataset Information

Transcriptome-guided amyloid imaging genetic analysis via a novel structured sparse learning algorithm.

Publications

Transcriptome-guided amyloid imaging genetic analysis via a novel structured sparse learning algorithm.

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