Sparse regulatory networks

DOI10.1214/10-AOAS350MaRDI QIDQ993240zbMATH OpenWikidataFDO

Authors Gareth M. James, Chiara Sabatti, Nengfeng Zhou, Ji Zhu

Publication date 10 September 2010

Published in The Annals of Applied Statistics (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1011.1798

zbMATH Keywords

transcription regulation networksE. coli\(L_1\) penaltysparse network

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Biochemistry, molecular biology (92C40) Genetics and epigenetics (92D10)

Abstract: In many organisms the expression levels of each gene are controlled by the activation levels of known "Transcription Factors" (TF). A problem of considerable interest is that of estimating the "Transcription Regulation Networks" (TRN) relating the TFs and genes. While the expression levels of genes can be observed, the activation levels of the corresponding TFs are usually unknown, greatly increasing the difficulty of the problem. Based on previous experimental work, it is often the case that partial information about the TRN is available. For example, certain TFs may be known to regulate a given gene or in other cases a connection may be predicted with a certain probability. In general, the biology of the problem indicates there will be very few connections between TFs and genes. Several methods have been proposed for estimating TRNs. However, they all suffer from problems such as unrealistic assumptions about prior knowledge of the network structure or computational limitations. We propose a new approach that can directly utilize prior information about the network structure in conjunction with observed gene expression data to estimate the TRN. Our approach uses $L_1$ penalties on the network to ensure a sparse structure. This has the advantage of being computationally efficient as well as making many fewer assumptions about the network structure. We use our methodology to construct the TRN for E. coli and show that the estimate is biologically sensible and compares favorably with previous estimates.

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Cited in

(4)

• Probabilistic graphical modelling of causal effects among the occurrences of transcription factors in DNA sequence
• Structure-function relations are subtle in genetic regulatory networks
• Sparse factor model for co-expression networks with an application using prior biological knowledge
• Robust Gaussian graphical modeling via \(l_{1}\) penalization

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Uses Software

• gNCA
• PMA

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