Dataset Information

Combining Partially Overlapping Multi-Omics Data in Databases Using Relationship Matrices.

ABSTRACT: Private and public breeding programs, as well as companies and universities, have developed different genomics technologies that have resulted in the generation of unprecedented amounts of sequence data, which bring new challenges in terms of data management, query, and analysis. The magnitude and complexity of these datasets bring new challenges but also an opportunity to use the data available as a whole. Detailed phenotype data, combined with increasing amounts of genomic data, have an enormous potential to accelerate the identification of key traits to improve our understanding of quantitative genetics. Data harmonization enables cross-national and international comparative research, facilitating the extraction of new scientific knowledge. In this paper, we address the complex issue of combining high dimensional and unbalanced omics data. More specifically, we propose a covariance-based method for combining partial datasets in the genotype to phenotype spectrum. This method can be used to combine partially overlapping relationship/covariance matrices. Here, we show with applications that our approach might be advantageous to feature imputation based approaches; we demonstrate how this method can be used in genomic prediction using heterogeneous marker data and also how to combine the data from multiple phenotypic experiments to make inferences about previously unobserved trait relationships. Our results demonstrate that it is possible to harmonize datasets to improve available information across gene-banks, data repositories, or other data resources.

SUBMITTER: Akdemir D

PROVIDER: S-EPMC7381228 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Combining Partially Overlapping Multi-Omics Data in Databases Using Relationship Matrices.

Akdemir Deniz D Knox Ron R Isidro Y Sánchez Julio J

Frontiers in plant science 20200714

Private and public breeding programs, as well as companies and universities, have developed different genomics technologies that have resulted in the generation of unprecedented amounts of sequence data, which bring new challenges in terms of data management, query, and analysis. The magnitude and complexity of these datasets bring new challenges but also an opportunity to use the data available as a whole. Detailed phenotype data, combined with increasing amounts of genomic data, have an enormo ...[more]

PMID: 32765543

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Project description:As omics measurements profiled on different molecular layers are interconnected, integrative approaches that incorporate the regulatory effect from multi-level omics data are needed. When the multi-level omics data are from the same individuals, gene expression (GE) clusters can be identified using information from regulators like genetic variants and DNA methylation. When the multi-level omics data are from different individuals, the choice of integration approaches is limited. We developed an approach to improve GE clustering from microarray data by integrating regulatory data from different but partially overlapping sets of individuals. We achieve this through (1) decomposing gene expression into the regulated component and the other component that is not regulated by measured factors, (2) optimizing the clustering goodness-of-fit objective function. We do not require the availability of different omics measurements on all individuals. A certain amount of individual overlap between GE data and the regulatory data is adequate for modeling the regulation, thus improving GE clustering. A simulation study shows that the performance of the proposed approach depends on the strength of the GE-regulator relationship, degree of missingness, data dimensionality, sample size, and the number of clusters. Across the various simulation settings, the proposed method shows competitive performance in terms of accuracy compared to the alternative K-means clustering method, especially when the clustering structure is due mostly to the regulated component, rather than the unregulated component. We further validate the approach with an application to 8,902 Framingham Heart Study participants with data on up to 17,873 genes and regulation information of DNA methylation and genotype from different but partially overlapping sets of participants. We identify clustering structures of genes associated with pulmonary function while incorporating the predicted regulation effect from the measured regulators. We further investigate the over-representation of these GE clusters in pathways of other diseases that may be related to lung function and respiratory health. We propose a novel approach for clustering GE with the assistance of regulatory data that allowed for different but partially overlapping sets of individuals to be included in different omics data.

Project description:Multi-omics data, that is, datasets containing different types of high-dimensional molecular variables, are increasingly often generated for the investigation of various diseases. Nevertheless, questions remain regarding the usefulness of multi-omics data for the prediction of disease outcomes such as survival time. It is also unclear which methods are most appropriate to derive such prediction models. We aim to give some answers to these questions through a large-scale benchmark study using real data. Different prediction methods from machine learning and statistics were applied on 18 multi-omics cancer datasets (35 to 1000 observations, up to 100 000 variables) from the database 'The Cancer Genome Atlas' (TCGA). The considered outcome was the (censored) survival time. Eleven methods based on boosting, penalized regression and random forest were compared, comprising both methods that do and that do not take the group structure of the omics variables into account. The Kaplan-Meier estimate and a Cox model using only clinical variables were used as reference methods. The methods were compared using several repetitions of 5-fold cross-validation. Uno's C-index and the integrated Brier score served as performance metrics. The results indicate that methods taking into account the multi-omics structure have a slightly better prediction performance. Taking this structure into account can protect the predictive information in low-dimensional groups-especially clinical variables-from not being exploited during prediction. Moreover, only the block forest method outperformed the Cox model on average, and only slightly. This indicates, as a by-product of our study, that in the considered TCGA studies the utility of multi-omics data for prediction purposes was limited. Contact:moritz.herrmann@stat.uni-muenchen.de, +49 89 2180 3198 Supplementary information: Supplementary data are available at Briefings in Bioinformatics online. All analyses are reproducible using R code freely available on Github.

Dataset Information

Combining Partially Overlapping Multi-Omics Data in Databases Using Relationship Matrices.

Publications

Combining Partially Overlapping Multi-Omics Data in Databases Using Relationship Matrices.

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