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A new insight into underlying disease mechanism through semi-parametric latent differential network model

BACKGROUND: In genomic studies, to investigate how the structure of a genetic network differs between two experiment conditions is a very interesting but challenging problem, especially in high-dimensional setting. Existing literatures mostly focus on differential network modelling for continuous da...

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Autores principales: He, Yong, Ji, Jiadong, Xie, Lei, Zhang, Xinsheng, Xue, Fuzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309076/
https://www.ncbi.nlm.nih.gov/pubmed/30591011
http://dx.doi.org/10.1186/s12859-018-2461-2
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author He, Yong
Ji, Jiadong
Xie, Lei
Zhang, Xinsheng
Xue, Fuzhong
author_facet He, Yong
Ji, Jiadong
Xie, Lei
Zhang, Xinsheng
Xue, Fuzhong
author_sort He, Yong
collection PubMed
description BACKGROUND: In genomic studies, to investigate how the structure of a genetic network differs between two experiment conditions is a very interesting but challenging problem, especially in high-dimensional setting. Existing literatures mostly focus on differential network modelling for continuous data. However, in real application, we may encounter discrete data or mixed data, which urges us to propose a unified differential network modelling for various data types. RESULTS: We propose a unified latent Gaussian copula differential network model which provides deeper understanding of the unknown mechanism than that among the observed variables. Adaptive rank-based estimation approaches are proposed with the assumption that the true differential network is sparse. The adaptive estimation approaches do not require precision matrices to be sparse, and thus can allow the individual networks to contain hub nodes. Theoretical analysis shows that the proposed methods achieve the same parametric convergence rate for both the difference of the precision matrices estimation and differential structure recovery, which means that the extra modeling flexibility comes at almost no cost of statistical efficiency. Besides theoretical analysis, thorough numerical simulations are conducted to compare the empirical performance of the proposed methods with some other state-of-the-art methods. The result shows that the proposed methods work quite well for various data types. The proposed method is then applied on gene expression data associated with lung cancer to illustrate its empirical usefulness. CONCLUSIONS: The proposed latent variable differential network models allows for various data-types and thus are more flexible, which also provide deeper understanding of the unknown mechanism than that among the observed variables. Theoretical analysis, numerical simulation and real application all demonstrate the great advantages of the latent differential network modelling and thus are highly recommended. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2461-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-63090762019-01-03 A new insight into underlying disease mechanism through semi-parametric latent differential network model He, Yong Ji, Jiadong Xie, Lei Zhang, Xinsheng Xue, Fuzhong BMC Bioinformatics Research BACKGROUND: In genomic studies, to investigate how the structure of a genetic network differs between two experiment conditions is a very interesting but challenging problem, especially in high-dimensional setting. Existing literatures mostly focus on differential network modelling for continuous data. However, in real application, we may encounter discrete data or mixed data, which urges us to propose a unified differential network modelling for various data types. RESULTS: We propose a unified latent Gaussian copula differential network model which provides deeper understanding of the unknown mechanism than that among the observed variables. Adaptive rank-based estimation approaches are proposed with the assumption that the true differential network is sparse. The adaptive estimation approaches do not require precision matrices to be sparse, and thus can allow the individual networks to contain hub nodes. Theoretical analysis shows that the proposed methods achieve the same parametric convergence rate for both the difference of the precision matrices estimation and differential structure recovery, which means that the extra modeling flexibility comes at almost no cost of statistical efficiency. Besides theoretical analysis, thorough numerical simulations are conducted to compare the empirical performance of the proposed methods with some other state-of-the-art methods. The result shows that the proposed methods work quite well for various data types. The proposed method is then applied on gene expression data associated with lung cancer to illustrate its empirical usefulness. CONCLUSIONS: The proposed latent variable differential network models allows for various data-types and thus are more flexible, which also provide deeper understanding of the unknown mechanism than that among the observed variables. Theoretical analysis, numerical simulation and real application all demonstrate the great advantages of the latent differential network modelling and thus are highly recommended. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2461-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-28 /pmc/articles/PMC6309076/ /pubmed/30591011 http://dx.doi.org/10.1186/s12859-018-2461-2 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
He, Yong
Ji, Jiadong
Xie, Lei
Zhang, Xinsheng
Xue, Fuzhong
A new insight into underlying disease mechanism through semi-parametric latent differential network model
title A new insight into underlying disease mechanism through semi-parametric latent differential network model
title_full A new insight into underlying disease mechanism through semi-parametric latent differential network model
title_fullStr A new insight into underlying disease mechanism through semi-parametric latent differential network model
title_full_unstemmed A new insight into underlying disease mechanism through semi-parametric latent differential network model
title_short A new insight into underlying disease mechanism through semi-parametric latent differential network model
title_sort new insight into underlying disease mechanism through semi-parametric latent differential network model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309076/
https://www.ncbi.nlm.nih.gov/pubmed/30591011
http://dx.doi.org/10.1186/s12859-018-2461-2
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