Integrated in silico analyses of regulatory and metabolic networks of Synechococcus sp. PCC 7002 reveal relationships between gene centrality and essentiality
Abstract
Cyanobacteria dynamically relay environmental inputs to intracellular adaptations through a coordinated adjustment of photosynthetic efficiency and carbon processing rates. The output of such adaptations is reflected through changes in transcriptional patterns and metabolic flux distributions that ultimately define growth strategy. To address interrelationships between metabolism and regulation, we performed integrative analyses of metabolic and gene co-expression networks in a model cyanobacterium, Synechococcus sp. PCC 7002. Centrality analyses using the gene co-expression network identified a set of key genes, which were defined here as ‘topologically important.’ Parallel in silico gene knock-out simulations, using the genome-scale metabolic network, classified what we termed as ‘functionally important’ genes, deletion of which affected growth or metabolism. A strong positive correlation was observed between topologically and functionally important genes. Functionally important genes exhibited variable levels of topological centrality; however, the majority of topologically central genes were found to be functionally essential for growth. Subsequent functional enrichment analysis revealed that both functionally and topologically important genes in Synechococcus sp. PCC 7002 are predominantly associated with translation and energy metabolism, two cellular processes critical for growth. This research demonstrates how synergistic network-level analyses can be used for reconciliation of metabolic and gene expression data to uncover fundamental biologicalmore »
- Authors:
- Publication Date:
- Research Org.:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1182919
- Report Number(s):
- PNNL-SA-109173
KP1601010
- Grant/Contract Number:
- AC05-76RL01830
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Life, 5(2):1127-1140
- Additional Journal Information:
- Journal Name: Life, 5(2):1127-1140
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; silico analyses; metabolic networks; synechococcus sp. PCC 7002
Citation Formats
Song, Hyun-Seob, McClure, Ryan S., Bernstein, Hans C., Overall, Christopher C., Hill, Eric A., and Beliaev, Alex S. Integrated in silico analyses of regulatory and metabolic networks of Synechococcus sp. PCC 7002 reveal relationships between gene centrality and essentiality. United States: N. p., 2015.
Web. doi:10.3390/life5021127.
Song, Hyun-Seob, McClure, Ryan S., Bernstein, Hans C., Overall, Christopher C., Hill, Eric A., & Beliaev, Alex S. Integrated in silico analyses of regulatory and metabolic networks of Synechococcus sp. PCC 7002 reveal relationships between gene centrality and essentiality. United States. https://doi.org/10.3390/life5021127
Song, Hyun-Seob, McClure, Ryan S., Bernstein, Hans C., Overall, Christopher C., Hill, Eric A., and Beliaev, Alex S. Fri .
"Integrated in silico analyses of regulatory and metabolic networks of Synechococcus sp. PCC 7002 reveal relationships between gene centrality and essentiality". United States. https://doi.org/10.3390/life5021127. https://www.osti.gov/servlets/purl/1182919.
@article{osti_1182919,
title = {Integrated in silico analyses of regulatory and metabolic networks of Synechococcus sp. PCC 7002 reveal relationships between gene centrality and essentiality},
author = {Song, Hyun-Seob and McClure, Ryan S. and Bernstein, Hans C. and Overall, Christopher C. and Hill, Eric A. and Beliaev, Alex S.},
abstractNote = {Cyanobacteria dynamically relay environmental inputs to intracellular adaptations through a coordinated adjustment of photosynthetic efficiency and carbon processing rates. The output of such adaptations is reflected through changes in transcriptional patterns and metabolic flux distributions that ultimately define growth strategy. To address interrelationships between metabolism and regulation, we performed integrative analyses of metabolic and gene co-expression networks in a model cyanobacterium, Synechococcus sp. PCC 7002. Centrality analyses using the gene co-expression network identified a set of key genes, which were defined here as ‘topologically important.’ Parallel in silico gene knock-out simulations, using the genome-scale metabolic network, classified what we termed as ‘functionally important’ genes, deletion of which affected growth or metabolism. A strong positive correlation was observed between topologically and functionally important genes. Functionally important genes exhibited variable levels of topological centrality; however, the majority of topologically central genes were found to be functionally essential for growth. Subsequent functional enrichment analysis revealed that both functionally and topologically important genes in Synechococcus sp. PCC 7002 are predominantly associated with translation and energy metabolism, two cellular processes critical for growth. This research demonstrates how synergistic network-level analyses can be used for reconciliation of metabolic and gene expression data to uncover fundamental biological principles.},
doi = {10.3390/life5021127},
journal = {Life, 5(2):1127-1140},
number = ,
volume = ,
place = {United States},
year = {Fri Mar 27 00:00:00 EDT 2015},
month = {Fri Mar 27 00:00:00 EDT 2015}
}
Works referenced in this record:
Effect of mono- and dichromatic light quality on growth rates and photosynthetic performance of Synechococcus sp. PCC 7002
journal, September 2014
- Bernstein, Hans C.; Konopka, Allan; Melnicki, Matthew R.
- Frontiers in Microbiology, Vol. 5
The phycobilisome, a light-harvesting complex responsive to environmental conditions.
journal, January 1993
- Grossman, A. R.; Schaefer, M. R.; Chiang, G. G.
- Microbiological Reviews, Vol. 57, Issue 3
Toward a systems-level understanding of gene regulatory, protein interaction, and metabolic networks in cyanobacteria
journal, July 2014
- Hernández-Prieto, Miguel A.; Semeniuk, Trudi A.; Futschik, Matthias E.
- Frontiers in Genetics, Vol. 5
Microbial Pathogenesis: Genomics and Beyond
journal, May 1997
- Strauss, E. J.
- Science, Vol. 276, Issue 5313
Evolutionary instability of operon structures disclosed by sequence comparisons of complete microbial genomes
journal, March 1999
- Itoh, T.; Takemoto, K.; Mori, H.
- Molecular Biology and Evolution, Vol. 16, Issue 3
High-throughput generation, optimization and analysis of genome-scale metabolic models
journal, August 2010
- Henry, Christopher S.; DeJongh, Matthew; Best, Aaron A.
- Nature Biotechnology, Vol. 28, Issue 9
A protocol for generating a high-quality genome-scale metabolic reconstruction
journal, January 2010
- Thiele, Ines; Palsson, Bernhard Ø
- Nature Protocols, Vol. 5, Issue 1
Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p
journal, April 2009
- Moxley, J. F.; Jewett, M. C.; Antoniewicz, M. R.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 16
The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli
journal, June 2008
- Feist, Adam M.; Palsson, Bernhard Ø
- Nature Biotechnology, Vol. 26, Issue 6
Applications of genome‐scale metabolic reconstructions
journal, January 2009
- Oberhardt, Matthew A.; Palsson, Bernhard Ø; Papin, Jason A.
- Molecular Systems Biology, Vol. 5, Issue 1
Inferring the relation between transcriptional and posttranscriptional regulation from expression compendia
journal, January 2014
- Ishchukov, Ivan; Wu, Yan; Van Puyvelde, Sandra
- BMC Microbiology, Vol. 14, Issue 1
Large-Scale Mapping and Validation of Escherichia coli Transcriptional Regulation from a Compendium of Expression Profiles
journal, January 2007
- Faith, Jeremiah J.; Hayete, Boris; Thaden, Joshua T.
- PLoS Biology, Vol. 5, Issue 1
Massive-Scale Gene Co-Expression Network Construction and Robustness Testing Using Random Matrix Theory
journal, February 2013
- Gibson, Scott M.; Ficklin, Stephen P.; Isaacson, Sven
- PLoS ONE, Vol. 8, Issue 2
Using the Topology of Metabolic Networks to Predict Viability of Mutant Strains
journal, September 2006
- Wunderlich, Zeba; Mirny, Leonid A.
- Biophysical Journal, Vol. 91, Issue 6
Functional essentiality from topology features in metabolic networks: A case study in yeast
journal, August 2005
- Palumbo, Maria Concetta; Colosimo, Alfredo; Giuliani, Alessandro
- FEBS Letters, Vol. 579, Issue 21
Properties of Metabolic Networks: Structure versus Function
journal, January 2005
- Mahadevan, R.; Palsson, B. O.
- Biophysical Journal, Vol. 88, Issue 1
How to identify essential genes from molecular networks?
journal, October 2009
- del Rio, Gabriel; Koschützki, Dirk; Coello, Gerardo
- BMC Systems Biology, Vol. 3, Issue 1
Co-occurrence of phycocyanin- and phycoerythrin-rich S ynechococcus in subtropical estuarine and coastal waters of Hong Kong: PE-rich and PC-rich Synechococcus in subtropical coastal waters
journal, October 2013
- Liu, Hongbin; Jing, Hongmei; Wong, Thomas H. C.
- Environmental Microbiology Reports, Vol. 6, Issue 1
Studies on Marine Blue-Green Algae
journal, January 1962
- Van Baalen, Chase
- Botanica Marina, Vol. 4, Issue 1-2
Transcription Profiling of the Model Cyanobacterium Synechococcus sp. Strain PCC 7002 by Next-Gen (SOLiD™) Sequencing of cDNA
journal, January 2011
- Ludwig, Marcus; Bryant, Donald A.
- Frontiers in Microbiology, Vol. 2
Synechococcus sp. Strain PCC 7002 Transcriptome: Acclimation to Temperature, Salinity, Oxidative Stress, and Mixotrophic Growth Conditions
journal, January 2012
- Ludwig, Marcus; Bryant, Donald A.
- Frontiers in Microbiology, Vol. 3
Inference of interactions in cyanobacterial–heterotrophic co-cultures via transcriptome sequencing
journal, April 2014
- Beliaev, Alexander S.; Romine, Margie F.; Serres, Margrethe
- The ISME Journal, Vol. 8, Issue 11
Acclimation of the Global Transcriptome of the Cyanobacterium Synechococcus sp. Strain PCC 7002 to Nutrient Limitations and Different Nitrogen Sources
journal, January 2012
- Ludwig, Marcus; Bryant, Donald A.
- Frontiers in Microbiology, Vol. 3
Feedback-controlled LED photobioreactor for photophysiological studies of cyanobacteria
journal, April 2013
- Melnicki, Matthew R.; Pinchuk, Grigoriy E.; Hill, Eric A.
- Bioresource Technology, Vol. 134
Computational analysis of bacterial RNA-Seq data
journal, May 2013
- McClure, Ryan; Balasubramanian, Divya; Sun, Yan
- Nucleic Acids Research, Vol. 41, Issue 14
Identification of Functional Differences in Metabolic Networks Using Comparative Genomics and Constraint-Based Models
journal, April 2012
- Hamilton, Joshua J.; Reed, Jennifer L.
- PLoS ONE, Vol. 7, Issue 4
Prediction of Metabolic Flux Distribution from Gene Expression Data Based on the Flux Minimization Principle
journal, November 2014
- Song, Hyun-Seob; Reifman, Jaques; Wallqvist, Anders
- PLoS ONE, Vol. 9, Issue 11
Analysis of optimality in natural and perturbed metabolic networks
journal, November 2002
- Segre, D.; Vitkup, D.; Church, G. M.
- Proceedings of the National Academy of Sciences, Vol. 99, Issue 23
Node centrality in weighted networks: Generalizing degree and shortest paths
journal, July 2010
- Opsahl, Tore; Agneessens, Filip; Skvoretz, John
- Social Networks, Vol. 32, Issue 3
Error and attack tolerance of complex networks
journal, July 2000
- Albert, Réka; Jeong, Hawoong; Barabási, Albert-László
- Nature, Vol. 406, Issue 6794
System-Wide Pollution of Biomedical Data: Consequence of the Search for Hub Genes of Hepatocellular Carcinoma Without Spatiotemporal Consideration
journal, January 2021
- Sharma, Ankush; Colonna, Giovanni
- Molecular Diagnosis & Therapy, Vol. 25, Issue 1
Feedback-controlled LED photobioreactor for photophysiological studies of cyanobacteria
journal, April 2013
- Melnicki, Matthew R.; Pinchuk, Grigoriy E.; Hill, Eric A.
- Bioresource Technology, Vol. 134
Functional essentiality from topology features in metabolic networks: A case study in yeast
journal, August 2005
- Palumbo, Maria Concetta; Colosimo, Alfredo; Giuliani, Alessandro
- FEBS Letters, Vol. 579, Issue 21
Node centrality in weighted networks: Generalizing degree and shortest paths
journal, July 2010
- Opsahl, Tore; Agneessens, Filip; Skvoretz, John
- Social Networks, Vol. 32, Issue 3
Inference of interactions in cyanobacterial–heterotrophic co-cultures via transcriptome sequencing
journal, April 2014
- Beliaev, Alexander S.; Romine, Margie F.; Serres, Margrethe
- The ISME Journal, Vol. 8, Issue 11
Applications of genome‐scale metabolic reconstructions
journal, January 2009
- Oberhardt, Matthew A.; Palsson, Bernhard Ø; Papin, Jason A.
- Molecular Systems Biology, Vol. 5, Issue 1
High-throughput generation, optimization and analysis of genome-scale metabolic models
journal, August 2010
- Henry, Christopher S.; DeJongh, Matthew; Best, Aaron A.
- Nature Biotechnology, Vol. 28, Issue 9
The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli
journal, June 2008
- Feist, Adam M.; Palsson, Bernhard Ø
- Nature Biotechnology, Vol. 26, Issue 6
A protocol for generating a high-quality genome-scale metabolic reconstruction
journal, January 2010
- Thiele, Ines; Palsson, Bernhard Ø
- Nature Protocols, Vol. 5, Issue 1
Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p
journal, April 2009
- Moxley, J. F.; Jewett, M. C.; Antoniewicz, M. R.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 16
Analysis of optimality in natural and perturbed metabolic networks
journal, November 2002
- Segre, D.; Vitkup, D.; Church, G. M.
- Proceedings of the National Academy of Sciences, Vol. 99, Issue 23
Evolutionary instability of operon structures disclosed by sequence comparisons of complete microbial genomes
journal, March 1999
- Itoh, T.; Takemoto, K.; Mori, H.
- Molecular Biology and Evolution, Vol. 16, Issue 3
Overview of metrics and their correlation patterns for multiple-metric topology analysis on heterogeneous graph ensembles
journal, January 2012
- Bounova, Gergana; de Weck, Olivier
- Physical Review E, Vol. 85, Issue 1
Co-occurrence of phycocyanin- and phycoerythrin-rich S ynechococcus in subtropical estuarine and coastal waters of Hong Kong: PE-rich and PC-rich Synechococcus in subtropical coastal waters
journal, October 2013
- Liu, Hongbin; Jing, Hongmei; Wong, Thomas H. C.
- Environmental Microbiology Reports, Vol. 6, Issue 1
Microbial Pathogenesis: Genomics and Beyond
journal, May 1997
- Strauss, E. J.
- Science, Vol. 276, Issue 5313
Abundance and Distribution of Synechococcus spp. and Cyanophages in the Chesapeake Bay
journal, August 2011
- Wang, Kui; Wommack, K. Eric; Chen, Feng
- Applied and Environmental Microbiology, Vol. 77, Issue 21
The phycobilisome, a light-harvesting complex responsive to environmental conditions.
journal, January 1993
- Grossman, A. R.; Schaefer, M. R.; Chiang, G. G.
- Microbiological Reviews, Vol. 57, Issue 3
Inferring the relation between transcriptional and posttranscriptional regulation from expression compendia
journal, January 2014
- Ishchukov, Ivan; Wu, Yan; Van Puyvelde, Sandra
- BMC Microbiology, Vol. 14, Issue 1
How to identify essential genes from molecular networks?
journal, October 2009
- del Rio, Gabriel; Koschützki, Dirk; Coello, Gerardo
- BMC Systems Biology, Vol. 3, Issue 1
Large-Scale Mapping and Validation of Escherichia coli Transcriptional Regulation from a Compendium of Expression Profiles
journal, January 2007
- Faith, Jeremiah J.; Hayete, Boris; Thaden, Joshua T.
- PLoS Biology, Vol. 5, Issue 1
Identification of Functional Differences in Metabolic Networks Using Comparative Genomics and Constraint-Based Models
journal, April 2012
- Hamilton, Joshua J.; Reed, Jennifer L.
- PLoS ONE, Vol. 7, Issue 4
Massive-Scale Gene Co-Expression Network Construction and Robustness Testing Using Random Matrix Theory
journal, February 2013
- Gibson, Scott M.; Ficklin, Stephen P.; Isaacson, Sven
- PLoS ONE, Vol. 8, Issue 2
Studies on Marine Blue-Green Algae
journal, January 1962
- Van Baalen, Chase
- Botanica Marina, Vol. 4, Issue 1-2
Using the Topology of Metabolic Networks to Predict Viability of Mutant Strains
journal, September 2006
- Wunderlich, Zeba; Mirny, Leonid A.
- Biophysical Journal, Vol. 91, Issue 6
Toward a systems-level understanding of gene regulatory, protein interaction, and metabolic networks in cyanobacteria
journal, July 2014
- Hernández-Prieto, Miguel A.; Semeniuk, Trudi A.; Futschik, Matthias E.
- Frontiers in Genetics, Vol. 5
Synechococcus sp. Strain PCC 7002 Transcriptome: Acclimation to Temperature, Salinity, Oxidative Stress, and Mixotrophic Growth Conditions
journal, January 2012
- Ludwig, Marcus; Bryant, Donald A.
- Frontiers in Microbiology, Vol. 3
Effect of mono- and dichromatic light quality on growth rates and photosynthetic performance of Synechococcus sp. PCC 7002
journal, September 2014
- Bernstein, Hans C.; Konopka, Allan; Melnicki, Matthew R.
- Frontiers in Microbiology, Vol. 5
Works referencing / citing this record:
Species-specific transcriptomic network inference of interspecies interactions
journal, May 2018
- McClure, Ryan S.; Overall, Christopher C.; Hill, Eric A.
- The ISME Journal, Vol. 12, Issue 8
In Silico Knockout Screening of Plasmodium falciparum Reactions and Prediction of Novel Essential Reactions by Analysing the Metabolic Network
journal, January 2018
- Oyelade, Jelili; Isewon, Itunuoluwa; Uwoghiren, Efosa
- BioMed Research International, Vol. 2018
Unified feature association networks through integration of transcriptomic and proteomic data
journal, September 2019
- McClure, Ryan S.; Wendler, Jason P.; Adkins, Joshua N.
- PLOS Computational Biology, Vol. 15, Issue 9
Integrating Ecological and Engineering Concepts of Resilience in Microbial Communities
journal, December 2015
- Song, Hyun-Seob; Renslow, Ryan S.; Fredrickson, Jim K.
- Frontiers in Microbiology, Vol. 6
Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection
journal, October 2019
- Zhu, Tianmou; McClure, Ryan; Harrison, Odile B.
- Vaccines, Vol. 7, Issue 4
Unified feature association networks through integration of transcriptomic and proteomic data
text, January 2019
- P., Wendler, Jason; L., Deatherage Kaiser, Brooke; Kristie, Oxford,
- The University of North Carolina at Chapel Hill University Libraries
Engineering photosynthetic production of L-lysine
journal, November 2017
- Korosh, Travis C.; Markley, Andrew L.; Clark, Ryan L.
- Metabolic Engineering, Vol. 44
Global Network Analysis of Neisseria gonorrhoeae Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection
journal, February 2020
- McClure, Ryan; Sunkavalli, Ashwini; Balzano, Phillip M.
- mSystems, Vol. 5, Issue 1
Unified feature association networks through integration of transcriptomic and proteomic data
journal, September 2019
- McClure, Ryan S.; Wendler, Jason P.; Adkins, Joshua N.
- PLOS Computational Biology, Vol. 15, Issue 9
Integrating Ecological and Engineering Concepts of Resilience in Microbial Communities
journal, December 2015
- Song, Hyun-Seob; Renslow, Ryan S.; Fredrickson, Jim K.
- Frontiers in Microbiology, Vol. 6
Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection
journal, October 2019
- Zhu, Tianmou; McClure, Ryan; Harrison, Odile B.
- Vaccines, Vol. 7, Issue 4