Dataset Information

Multi-Task Sparse Canonical Correlation Analysis with Application to Multi-Modal Brain Imaging Genetics.

ABSTRACT: Brain imaging genetics studies the genetic basis of brain structures and functionalities via integrating genotypic data such as single nucleotide polymorphisms (SNPs) and imaging quantitative traits (QTs). In this area, both multi-task learning (MTL) and sparse canonical correlation analysis (SCCA) methods are widely used since they are superior to those independent and pairwise univariate analysis. MTL methods generally incorporate a few of QTs and could not select features from multiple QTs; while SCCA methods typically employ one modality of QTs to study its association with SNPs. Both MTL and SCCA are computational expensive as the number of SNPs increases. In this paper, we propose a novel multi-task SCCA (MTSCCA) method to identify bi-multivariate associations between SNPs and multi-modal imaging QTs. MTSCCA could make use of the complementary information carried by different imaging modalities. MTSCCA enforces sparsity at the group level via the G_2,1-norm, and jointly selects features across multiple tasks for SNPs and QTs via the l_2,1-norm. A fast optimization algorithm is proposed using the grouping information of SNPs. Compared with conventional SCCA methods, MTSCCA obtains better correlation coefficients and canonical weights patterns. In addition, MTSCCA runs very fast and easy-to-implement, indicating its potential power in genome-wide brain-wide imaging genetics.

SUBMITTER: Du L

PROVIDER: S-EPMC7156329 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:MotivationIdentifying 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.ResultsWe 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 implementationThe software and simulation data are publicly available at https://github.com/dulei323/TMTSCCA.Supplementary informationSupplementary data are available at Bioinformatics online.

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Multi-Task Sparse Canonical Correlation Analysis with Application to Multi-Modal Brain Imaging Genetics.

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