Dataset Information

Sparse canonical methods for biological data integration: application to a cross-platform study.

ABSTRACT:

Background

In the context of systems biology, few sparse approaches have been proposed so far to integrate several data sets. It is however an important and fundamental issue that will be widely encountered in post genomic studies, when simultaneously analyzing transcriptomics, proteomics and metabolomics data using different platforms, so as to understand the mutual interactions between the different data sets. In this high dimensional setting, variable selection is crucial to give interpretable results. We focus on a sparse Partial Least Squares approach (sPLS) to handle two-block data sets, where the relationship between the two types of variables is known to be symmetric. Sparse PLS has been developed either for a regression or a canonical correlation framework and includes a built-in procedure to select variables while integrating data. To illustrate the canonical mode approach, we analyzed the NCI60 data sets, where two different platforms (cDNA and Affymetrix chips) were used to study the transcriptome of sixty cancer cell lines.

Results

We compare the results obtained with two other sparse or related canonical correlation approaches: CCA with Elastic Net penalization (CCA-EN) and Co-Inertia Analysis (CIA). The latter does not include a built-in procedure for variable selection and requires a two-step analysis. We stress the lack of statistical criteria to evaluate canonical correlation methods, which makes biological interpretation absolutely necessary to compare the different gene selections. We also propose comprehensive graphical representations of both samples and variables to facilitate the interpretation of the results.

Conclusion

sPLS and CCA-EN selected highly relevant genes and complementary findings from the two data sets, which enabled a detailed understanding of the molecular characteristics of several groups of cell lines. These two approaches were found to bring similar results, although they highlighted the same phenomenons with a different priority. They outperformed CIA that tended to select redundant information.

SUBMITTER: Le Cao KA

PROVIDER: S-EPMC2640358 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sparse canonical methods for biological data integration: application to a cross-platform study.

Lê Cao Kim-Anh KA Martin Pascal G P PG Robert-Granié Christèle C Besse Philippe P

BMC bioinformatics 20090126

<h4>Background</h4>In the context of systems biology, few sparse approaches have been proposed so far to integrate several data sets. It is however an important and fundamental issue that will be widely encountered in post genomic studies, when simultaneously analyzing transcriptomics, proteomics and metabolomics data using different platforms, so as to understand the mutual interactions between the different data sets. In this high dimensional setting, variable selection is crucial to give inte ...[more]

PMID: 19171069

Similar 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:BackgroundComparing metabolic profiles under different biological perturbations has become a powerful approach to investigating the functioning of cells. The profiles can be taken as single snapshots of a system, but more information is gained if they are measured longitudinally over time. The results are short time series consisting of relatively sparse data that cannot be analyzed effectively with standard time series techniques, such as autocorrelation and frequency domain methods. In this work, we study longitudinal time series profiles of glucose consumption in the yeast Saccharomyces cerevisiae under different temperatures and preconditioning regimens, which we obtained with methods of in vivo nuclear magnetic resonance (NMR) spectroscopy. For the statistical analysis we first fit several nonlinear mixed effect regression models to the longitudinal profiles and then used an ANOVA likelihood ratio method in order to test for significant differences between the profiles.ResultsThe proposed methods are capable of distinguishing metabolic time trends resulting from different treatments and associate significance levels to these differences. Among several nonlinear mixed-effects regression models tested, a three-parameter logistic function represents the data with highest accuracy. ANOVA and likelihood ratio tests suggest that there are significant differences between the glucose consumption rate profiles for cells that had been--or had not been--preconditioned by heat during growth. Furthermore, pair-wise t-tests reveal significant differences in the longitudinal profiles for glucose consumption rates between optimal conditions and heat stress, optimal and recovery conditions, and heat stress and recovery conditions (p-values <0.0001).ConclusionWe have developed a nonlinear mixed effects model that is appropriate for the analysis of sparse metabolic and physiological time profiles. The model permits sound statistical inference procedures, based on ANOVA likelihood ratio tests, for testing the significance of differences between short time course data under different biological perturbations.

Dataset Information

Sparse canonical methods for biological data integration: application to a cross-platform study.

Background

Results

Conclusion

Publications

Sparse canonical methods for biological data integration: application to a cross-platform study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets