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  Joint Modelling of Confounding Factors and Prominent Genetic Regulators Provides Increased Accuracy in Genetical Genomics Studies

Fusi, N., Stegle, O., & Lawrence, N. (2012). Joint Modelling of Confounding Factors and Prominent Genetic Regulators Provides Increased Accuracy in Genetical Genomics Studies. PLoS Computational Biology, 8(1), 1-9. doi:10.1371/journal.pcbi.1002330.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-B860-E Version Permalink: http://hdl.handle.net/21.11116/0000-0006-C59C-C
Genre: Journal Article

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Fusi, N, Author
Stegle, O1, Author              
Lawrence, ND, Author
Affiliations:
1Former Research Group Machine Learning and Computational Biology, Max Planck Institute for Intelligent Systems, Max Planck Society, DE, ou_1497664              

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 Abstract: Expression quantitative trait loci (eQTL) studies are an integral tool to investigate the genetic component of gene expression variation. A major challenge in the analysis of such studies are hidden confounding factors, such as unobserved covariates or unknown subtle environmental perturbations. These factors can induce a pronounced artifactual correlation structure in the expression profiles, which may create spurious false associations or mask real genetic association signals. Here, we report PANAMA (Probabilistic ANAlysis of genoMic dAta), a novel probabilistic model to account for confounding factors within an eQTL analysis. In contrast to previous methods, PANAMA learns hidden factors jointly with the effect of prominent genetic regulators. As a result, this new model can more accurately distinguish true genetic association signals from confounding variation. We applied our model and compared it to existing methods on different datasets and biological systems. PANAMA consistently performs better than alternative methods, and finds in particular substantially more trans regulators. Importantly, our approach not only identifies a greater number of associations, but also yields hits that are biologically more plausible and can be better reproduced between independent studies. A software implementation of PANAMA is freely available online at http://ml.sheffield.ac.uk/qtl/.

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 Dates: 2012-01
 Publication Status: Published online
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 Rev. Type: -
 Identifiers: DOI: 10.1371/journal.pcbi.1002330
eDoc: e1002330
BibTex Citekey: FusiSL2012
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Title: PLoS Computational Biology
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 8 (1) Sequence Number: - Start / End Page: 1 - 9 Identifier: ISSN: 1553-734X
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000017180_1