Multi-omics factor analysis: a framework for unsupervised integration of multi-omics data sets

Abstract Multi-omics studies promise the improved characterization of biological processes across molecular layers. However, methods for the unsupervised integration of the resulting heterogeneous data sets are lacking. We present Multi-Omics Factor Analysis (MOFA), a computational method for discov...

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Main Authors: Argelaguet, Ricard (Author) , Velten, Britta (Author) , Arnol, Damien (Author) , Dietrich, Sascha (Author) , Zenz, Thorsten (Author) , Marioni, John C (Author) , Buettner, Florian (Author) , Huber, Wolfgang (Author) , Stegle, Oliver (Author)
Format: Article (Journal)
Language:English
Published: 29 May 2018
In: Molecular systems biology
Year: 2018, Volume: 14, Issue: 6
ISSN:1744-4292
DOI:10.15252/msb.20178124
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/msb.20178124
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.15252/msb.20178124
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Author Notes:Ricard Argelaguet, Britta Velten, Damien Arnol, Sascha Dietrich, Thorsten Zenz, John C Marioni, Florian Buettner, Wolfgang Huber & Oliver Stegle
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Summary:Abstract Multi-omics studies promise the improved characterization of biological processes across molecular layers. However, methods for the unsupervised integration of the resulting heterogeneous data sets are lacking. We present Multi-Omics Factor Analysis (MOFA), a computational method for discovering the principal sources of variation in multi-omics data sets. MOFA infers a set of (hidden) factors that capture biological and technical sources of variability. It disentangles axes of heterogeneity that are shared across multiple modalities and those specific to individual data modalities. The learnt factors enable a variety of downstream analyses, including identification of sample subgroups, data imputation and the detection of outlier samples. We applied MOFA to a cohort of 200 patient samples of chronic lymphocytic leukaemia, profiled for somatic mutations, RNA expression, DNA methylation and ex vivo drug responses. MOFA identified major dimensions of disease heterogeneity, including immunoglobulin heavy-chain variable region status, trisomy of chromosome 12 and previously underappreciated drivers, such as response to oxidative stress. In a second application, we used MOFA to analyse single-cell multi-omics data, identifying coordinated transcriptional and epigenetic changes along cell differentiation.
Item Description:Gesehen am 03.06.2020
Physical Description:Online Resource
ISSN:1744-4292
DOI:10.15252/msb.20178124