Metabolic constraint-based refinement of transcriptional regulatory networks

PLoS Computational Biology
Sriram Chandrasekaran, Nathan D Price

Abstract

There is a strong need for computational frameworks that integrate different biological processes and data-types to unravel cellular regulation. Current efforts to reconstruct transcriptional regulatory networks (TRNs) focus primarily on proximal data such as gene co-expression and transcription factor (TF) binding. While such approaches enable rapid reconstruction of TRNs, the overwhelming combinatorics of possible networks limits identification of mechanistic regulatory interactions. Utilizing growth phenotypes and systems-level constraints to inform regulatory network reconstruction is an unmet challenge. We present our approach Gene Expression and Metabolism Integrated for Network Inference (GEMINI) that links a compendium of candidate regulatory interactions with the metabolic network to predict their systems-level effect on growth phenotypes. We then compare predictions with experimental phenotype data to select phenotype-consistent regulatory interactions. GEMINI makes use of the observation that only a small fraction of regulatory network states are compatible with a viable metabolic network, and outputs a regulatory network that is simultaneously consistent with the input genome-scale metabolic network model, gene expr...Continue Reading

References

Dec 7, 2000·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·N FriedmanD Pe'er
Apr 5, 2003·The Journal of Biological Chemistry·Elton T YoungTrey Ideker
Dec 4, 2003·Metabolic Engineering·R Mahadevan, C H Schilling
May 7, 2004·Nature·Markus W CovertBernhard O Palsson
Sep 3, 2004·Nature·Christopher T HarbisonRichard A Young
Oct 21, 2004·Nature Reviews. Microbiology·Nathan D PriceBernhard Ø Palsson
Mar 22, 2005·Nature Genetics·Katia BassoAndrea Califano
May 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Tomer ShlomiEytan Ruppin
Oct 6, 2005·Genome Research·Lars KuepferLars M Blank
Dec 17, 2005·Proceedings of the National Academy of Sciences of the United States of America·Christian L BarrettBernhard O Palsson
Dec 20, 2005·The Journal of Biological Chemistry·Naoya HashikawaHiroshi Sakurai
Mar 9, 2006·BMC Bioinformatics·Kenzie D MacIsaacErnest Fraenkel
Sep 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Haiyuan Yu, Mark Gerstein
Feb 15, 2007·Molecular Systems Biology·Mukesh BansalDiego di Bernardo
Apr 10, 2007·Nature Genetics·Zhanzhi HuVishwanath R Iyer
May 17, 2008·PLoS Computational Biology·Jong Min LeeJason A Papin
Aug 20, 2008·Nature Biotechnology·Tomer ShlomiEytan Ruppin
Oct 14, 2008·Nature Neuroscience·Michael C OldhamDaniel H Geschwind
Oct 22, 2008·Nature Chemical Biology·Richard Bonneau
Jan 1, 2009·Nature Reviews. Microbiology·Adam M FeistBernhard Ø Palsson
Mar 14, 2009·PLoS Computational Biology·Vinay Satish Kumar, Costas D Maranas
Mar 27, 2009·BMC Systems Biology·Monica L MoMarkus J Herrgård
Apr 22, 2009·Methods in Molecular Biology·M Madan BabuL Aravind
Dec 17, 2009·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Sydney Brenner
Mar 10, 2010·Nature Biotechnology·Jeffrey D OrthBernhard Ø Palsson
Aug 31, 2010·Nature Biotechnology·Christopher S HenryRick L Stevens
Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sriram Chandrasekaran, Nathan D Price
Oct 6, 2010·BMC Bioinformatics·Steinn Gudmundsson, Ines Thiele
Nov 10, 2010·PLoS Computational Biology·Dipak BaruaJennifer L Reed
Dec 24, 2010·Science·UNKNOWN modENCODE ConsortiumManolis Kellis
Dec 31, 2010·BMC Systems Biology·Ali R Zomorrodi, Costas D Maranas
Oct 1, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sriram ChandrasekaranGene E Robinson
Mar 1, 2012·PloS One·Jakub Orzechowski WestholmHans Ronne
Mar 1, 2012·Nature Reviews. Microbiology·Nathan E LewisBernhard O Palsson

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Citations

Oct 18, 2015·Briefings in Functional Genomics·Jie HouJianlin Cheng
Feb 18, 2015·Plant, Cell & Environment·David B MedeirosWagner L Araújo
Mar 12, 2015·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Óttar Rolfsson, Bernhard O Palsson
Nov 8, 2014·Computational and Structural Biotechnology Journal·Amanda K FisherRyan S Senger
Jun 17, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Benjamín J Sánchez, Jens Nielsen
May 23, 2015·Frontiers in Microbiology·Saheed ImamNathan D Price
Nov 9, 2014·Human Genetics·Donald GemanLaurent Younes
Mar 6, 2015·Frontiers in Plant Science·Nadine TöpferZoran Nikoloski
Sep 14, 2017·FEMS Yeast Research·Helder Lopes, Isabel Rocha
Sep 13, 2019·PLoS Computational Biology·Eberhard O Voit
May 29, 2021·Integrative and Comparative Biology·Sriram ChandrasekaranCharles Wolgemuth

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Methods Mentioned

BETA
gene knockout
ChIP

Software Mentioned

Flux Variability Analysis ( FVA )
ARACNE
Yeastract
GEMINI
MATLAB
Gene Expression and Metabolism Integrated for Network Inferenc...
COBRA
CLR
GNU Linear Programming Kit ( GLPK )
Flux Balance Analysis ( FBA )

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