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Identifying diagnosis-specific genotype-phenotype associations via joint multitask sparse canonical correlation analysis and classification.

ABSTRACT: MOTIVATION:Brain imaging genetics studies the complex associations between genotypic data such as single nucleotide polymorphisms (SNPs) and imaging quantitative traits (QTs). The neurodegenerative disorders usually exhibit the diversity and heterogeneity, originating from which different diagnostic groups might carry distinct imaging QTs, SNPs and their interactions. Sparse canonical correlation analysis (SCCA) is widely used to identify bi-multivariate genotype-phenotype associations. However, most existing SCCA methods are unsupervised, leading to an inability to identify diagnosis-specific genotype-phenotype associations. RESULTS:In this article, we propose a new joint multitask learning method, named MT-SCCALR, which absorbs the merits of both SCCA and logistic regression. MT-SCCALR learns genotype-phenotype associations of multiple tasks jointly, with each task focusing on identifying one diagnosis-specific genotype-phenotype pattern. Meanwhile, MT-SCCALR cannot only select relevant SNPs and imaging QTs for each diagnostic group alone, but also allows the selection of those shared by multiple diagnostic groups. We derive an efficient optimization algorithm whose convergence to a local optimum is guaranteed. Compared with two state-of-the-art methods, MT-SCCALR yields better or similar canonical correlation coefficients and classification performances. In addition, it owns much better discriminative canonical weight patterns of great interest than competitors. This demonstrates the power and capability of MTSCCAR in identifying diagnostically heterogeneous genotype-phenotype patterns, which would be helpful to understand the pathophysiology of brain disorders. AVAILABILITY AND IMPLEMENTATION:The software is publicly available at https://github.com/dulei323/MTSCCALR. SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.

SUBMITTER: Du L

PROVIDER: S-EPMC7355274 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Identifying diagnosis-specific genotype-phenotype associations via joint multitask sparse canonical correlation analysis and classification.

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

Bioinformatics (Oxford, England) 20200701 Suppl_1

<h4>Motivation</h4>Brain imaging genetics studies the complex associations between genotypic data such as single nucleotide polymorphisms (SNPs) and imaging quantitative traits (QTs). The neurodegenerative disorders usually exhibit the diversity and heterogeneity, originating from which different diagnostic groups might carry distinct imaging QTs, SNPs and their interactions. Sparse canonical correlation analysis (SCCA) is widely used to identify bi-multivariate genotype-phenotype associations. ...[more]

PMID: 32657360

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Project description:The local environment of the geographical origin of plants shaped their genetic variations through environmental adaptation. While the characteristics of the local environment correlate with the genotypes and other genomic features of the plants, they can also be indicative of genotype-phenotype associations providing additional information relevant to environmental dependence. In this study, we investigate how the geoclimatic features from the geographical origin of the Arabidopsis thaliana accessions can be integrated with genomic features for phenotype prediction and association analysis using advanced canonical correlation analysis (CCA). In particular, we propose a novel method called hierarchical canonical correlation analysis (HCCA) to combine mutations, gene expressions, and DNA methylations with geoclimatic features for informative coprojections of the features. HCCA uses a condition number of the cross-covariance between pairs of datasets to infer a hierarchical structure for applying CCA to combine the data. In the experiments on Arabidopsis thaliana data from 1001 Genomes and 1001 Epigenomes projects and climatic, atmospheric, and soil environmental variables combined by CLIMtools, HCCA provided a joint representation of the genomic data and geoclimate data for better prediction of the special flowering time at 10°C (FT10) of Arabidopsis thaliana. We also extended HCCA with information from a protein-protein interaction (PPI) network to guide the feature learning by imposing network modules onto the genomic features, which are shown to be useful for identifying genes with more coherent functions correlated with the geoclimatic features. The findings in this study suggest that environmental data comprise an important component in plant phenotype analysis. HCCA is a useful data integration technique for phenotype prediction, and a better understanding of the interactions between gene functions and environment as more useful functional information is introduced by coprojections of multiple genomic datasets.

Project description:The emergence of high-throughput genomic datasets from different sources and platforms (e.g., gene expression, single nucleotide polymorphisms (SNP), and copy number variation (CNV)) has greatly enhanced our understandings of the interplay of these genomic factors as well as their influences on the complex diseases. It is challenging to explore the relationship between these different types of genomic data sets. In this paper, we focus on a multivariate statistical method, canonical correlation analysis (CCA) method for this problem. Conventional CCA method does not work effectively if the number of data samples is significantly less than that of biomarkers, which is a typical case for genomic data (e.g., SNPs). Sparse CCA (sCCA) methods were introduced to overcome such difficulty, mostly using penalizations with l-1 norm (CCA-l1) or the combination of l-1and l-2 norm (CCA-elastic net). However, they overlook the structural or group effect within genomic data in the analysis, which often exist and are important (e.g., SNPs spanning a gene interact and work together as a group).We propose a new group sparse CCA method (CCA-sparse group) along with an effective numerical algorithm to study the mutual relationship between two different types of genomic data (i.e., SNP and gene expression). We then extend the model to a more general formulation that can include the existing sCCA models. We apply the model to feature/variable selection from two data sets and compare our group sparse CCA method with existing sCCA methods on both simulation and two real datasets (human gliomas data and NCI60 data). We use a graphical representation of the samples with a pair of canonical variates to demonstrate the discriminating characteristic of the selected features. Pathway analysis is further performed for biological interpretation of those features.The CCA-sparse group method incorporates group effects of features into the correlation analysis while performs individual feature selection simultaneously. It outperforms the two sCCA methods (CCA-l1 and CCA-group) by identifying the correlated features with more true positives while controlling total discordance at a lower level on the simulated data, even if the group effect does not exist or there are irrelevant features grouped with true correlated features. Compared with our proposed CCA-group sparse models, CCA-l1 tends to select less true correlated features while CCA-group inclines to select more redundant features.

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.

Dataset Information

Identifying diagnosis-specific genotype-phenotype associations via joint multitask sparse canonical correlation analysis and classification.

Publications

Identifying diagnosis-specific genotype-phenotype associations via joint multitask sparse canonical correlation analysis and classification.

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