Optimal design of gene knockout experiments for gene regulatory network inference

Bioinformatics
S M Minhaz Ud-Dean, Rudiyanto Gunawan

Abstract

We addressed the problem of inferring gene regulatory network (GRN) from gene expression data of knockout (KO) experiments. This inference is known to be underdetermined and the GRN is not identifiable from data. Past studies have shown that suboptimal design of experiments (DOE) contributes significantly to the identifiability issue of biological networks, including GRNs. However, optimizing DOE has received much less attention than developing methods for GRN inference. We developed REDuction of UnCertain Edges (REDUCE) algorithm for finding the optimal gene KO experiment for inferring directed graphs (digraphs) of GRNs. REDUCE employed ensemble inference to define uncertain gene interactions that could not be verified by prior data. The optimal experiment corresponds to the maximum number of uncertain interactions that could be verified by the resulting data. For this purpose, we introduced the concept of edge separatoid which gave a list of nodes (genes) that upon their removal would allow the verification of a particular gene interaction. Finally, we proposed a procedure that iterates over performing KO experiments, ensemble update and optimal DOE. The case studies including the inference of Escherichia coli GRN and DREAM 4...Continue Reading

Citations

May 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jesper TegnerJames J Collins
Jan 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Gustavo StolovitzkyJ C Roach
Aug 19, 2007·Molecular Systems Biology·Jun-ichi Kato, Masayuki Hashimoto
Apr 1, 2010·Nature Methods·Marloes H MaathuisPeter Bühlmann
Sep 9, 2011·Science Signaling·Robert J PrillGustavo Stolovitzky
Nov 1, 2011·BMC Systems Biology·Gábor SzederkényiAntonio A Alonso
Jul 17, 2012·Nature Methods·Daniel MarbachGustavo Stolovitzky
Jan 15, 2014·Biophysical Journal·Moritz LangJörg Stelling
Mar 29, 2014·Nature·Alistair R R ForrestYoshihide Hayashizaki
Aug 6, 2014·PloS One·S M Minhaz Ud-Dean, Rudiyanto Gunawan
Jun 17, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Pratish GawandRadhakrishnan Mahadevan

Related Concepts

Study
1,3-di-O-octadecenylglycero-2-phosphocholine
Classification
Alkalescens-Dispar Group
Genes
Knock-out
GRN
Gene Deletion Abnormality
Gene Deletion
Bio-Informatics

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