XL-MS: Protein cross-linking coupled with mass spectrometry.

Methods. 2015 Nov 1;89:54-63

Authors: Holding AN

Abstract
With the continuing trend to study larger and more complex systems, the application of protein cross-linking coupled with mass spectrometry (XL-MS) provides a varied toolkit perfectly suited to achieve these goals. By freezing the transient interactions through the formation of covalent bonds, XL-MS provides a vital insight into both the structure and organization of proteins in a wide variety of conditions. This review covers some of the established methods that underpin the field alongside the more recent developments that hold promise to further realize its potential in new directions.

PMID: 26079926 [PubMed - indexed for MEDLINE]

RNA-seq analysis of the transcriptional response to blue and red light in the extremophilic red alga, Cyanidioschyzon merolae.

Funct Integr Genomics. 2016 Sep 10;

Authors: Tardu M, Dikbas UM, Baris I, Kavakli IH

Abstract
Light is one of the main environmental cues that affects the physiology and behavior of many organisms. The effect of light on genome-wide transcriptional regulation has been well-studied in green algae and plants, but not in red algae. Cyanidioschyzon merolae is used as a model red algae, and is suitable for studies on transcriptomics because of its compact genome with a relatively small number of genes. In addition, complete genome sequences of the nucleus, mitochondrion, and chloroplast of this organism have been determined. Together, these attributes make C. merolae an ideal model organism to study the response to light stimuli at the transcriptional and the systems biology levels. Previous studies have shown that light significantly affects cell signaling in this organism, but there are no reports on its blue light- and red light-mediated transcriptional responses. We investigated the direct effects of blue and red light at the transcriptional level using RNA-seq. Blue and red lights were found to regulate 35 % of the total genes in C. merolae. Blue light affected the transcription of genes involved in protein synthesis while red light specifically regulated the transcription of genes involved in photosynthesis and DNA repair. Blue or red light regulated genes involved in carbon metabolism and pigment biosynthesis. Overall, our data showed that red and blue light regulate the majority of the cellular, cell division, and repair processes in C. merolae.

PMID: 27614431 [PubMed - as supplied by publisher]

A comprehensive approach to the molecular determinants of lifespan using a Boolean model of geroconversion.

Aging Cell. 2016 Sep 9;

Authors: Verlingue L, Dugourd A, Stoll G, Barillot E, Calzone L, Londoño-Vallejo A

Abstract
Altered molecular responses to insulin and growth factors (GF) are responsible for late-life shortening diseases such as type-2 diabetes mellitus (T2DM) and cancers. We have built a network of the signaling pathways that control S-phase entry and a specific type of senescence called geroconversion. We have translated this network into a Boolean model to study possible cell phenotype outcomes under diverse molecular signaling conditions. In the context of insulin resistance, the model was able to reproduce the variations of the senescence level observed in tissues related to T2DM's main morbidity and mortality. Furthermore, by calibrating the pharmacodynamics of mTOR inhibitors, we have been able to reproduce the dose-dependent effect of rapamycin on liver degeneration and lifespan expansion in wild-type and HER2-neu mice. Using the model, we have finally performed an in silico prospective screen of the risk-benefit ratio of rapamycin dosage for healthy lifespan expansion strategies. We present here a comprehensive prognostic and predictive systems biology tool for human aging.

PMID: 27613445 [PubMed - as supplied by publisher]

Systems biology integration of proteomic data in rodent models of depression reveals involvement of the immune response and glutamatergic signalling.

Proteomics Clin Appl. 2016 Sep 10;

Authors: Carboni L, Nguyen TP, Caberlotto L

Abstract
PURPOSE: The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study was to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease.
EXPERIMENTAL DESIGN: Network analysis was performed integrating pre-existing proteomic data from rodent models of depression. The IntAct mouse and the HRPD were used as reference protein-protein interaction databases. The functionality analyses of the networks were then performed by testing over-represented GO biological process terms and pathways.
RESULTS: Functional enrichment analyses of the networks revealed an association with molecular processes related to depression in humans, such as those involved in the immune response. Pathways impacted by clinically effective antidepressants were modulated, including glutamatergic signalling and neurotrophic responses. Moreover, dysregulations of proteins regulating energy metabolism and circadian rhythms were implicated. The comparison with protein pathways modulated in depressive patients revealed significant overlapping.
CONCLUSIONS AND CLINICAL RELEVANCE: This systems biology study supports the notion that animal models could contribute to the research into the biology and therapeutics of depression. This article is protected by copyright. All rights reserved.

PMID: 27612656 [PubMed - as supplied by publisher]

Different strategies of metabolic regulation in cyanobacteria: from transcriptional to biochemical control.

Sci Rep. 2016;6:33024

Authors: Jablonsky J, Papacek S, Hagemann M

Abstract
Cyanobacteria Synechococcus sp. PCC 7942 and Synechocystis sp. PCC 6803 show similar changes in the metabolic response to changed CO2 conditions but exhibit significant differences at the transcriptomic level. This study employs a systems biology approach to investigate the difference in metabolic regulation of Synechococcus sp. PCC 7942 and Synechocystis sp. PCC 6803. Presented multi-level kinetic model for Synechocystis sp. PCC 6803 is a new approach integrating and analysing metabolomic, transcriptomic and fluxomics data obtained under high and ambient CO2 levels. Modelling analysis revealed that higher number of different isozymes in Synechocystis 6803 improves homeostatic stability of several metabolites, especially 3PGA by 275%, against changes in gene expression, compared to Synechococcus sp. PCC 7942. Furthermore, both cyanobacteria have the same amount of phosphoglycerate mutases but Synechocystis 6803 exhibits only ~20% differences in their mRNA levels after shifts from high to ambient CO2 level, in comparison to ~500% differences in the case of Synechococcus sp. PCC 7942. These and other data imply that the biochemical control dominates over transcriptional regulation in Synechocystis 6803 to acclimate central carbon metabolism in the environment of variable inorganic carbon availability without extra cost carried by large changes in the proteome.

PMID: 27611502 [PubMed - as supplied by publisher]

A systems biology approach reveals major metabolic changes in the thermoacidophilic archaeon Sulfolobus solfataricus in response to the carbon source L-fucose versus D-glucose.

Mol Microbiol. 2016 Sep 9;

Authors: Wolf J, Stark H, Fafenrot K, Albersmeier A, Pham TK, Müller KB, Meyer B, Hoffmann L, Shen L, Albaum SP, Kouril T, Schmidt-Hohagen K, Neumann-Schaal M, Bräsen C, Kalinowski J, Wright PC, Albers SV, Schomburg D, Siebers B

Abstract
Archaea are characterised by a complex metabolism with many unique enzymes that differ from their bacterial and eukaryotic counterparts. The thermoacidophilic archaeon Sulfolobus solfataricus is known for its metabolic versatility and is able to utilize a great variety of different carbon sources. However, the underlying degradation pathways and their regulation are often unknown. In this work, we analyse growth on different carbon sources using an integrated systems biology approach. The comparison of growth on L-fucose and D-glucose allows first insights into the genome-wide changes in response to the two carbon sources and revealed a new pathway for L-fucose degradation in S. solfataricus. During growth on L-fucose we observed major changes in the central carbon metabolic network, as well as an increased activity of the glyoxylate bypass and the 3-hydroxypropionate/4-hydroxybutyrate cycle. Within the newly discovered pathway for L-fucose degradation the following key reactions were identified: (i) L-fucose oxidation to L-fuconate via a dehydrogenase, (ii) dehydration to 2-keto-3-deoxy-L-fuconate via dehydratase, (iii) 2-keto-3-deoxy-L-fuconate cleavage to pyruvate and L-lactaldehyde via aldolase and (iv) L-lactaldehyde conversion to L-lactate via aldehyde dehydrogenase. This pathway as well as L-fucose transport shows interesting overlaps to the D-arabinose pathway, representing another example for pathway promiscuity in Sulfolobus species. This article is protected by copyright. All rights reserved.

PMID: 27611014 [PubMed - as supplied by publisher]

TNIP2 is a hub protein in the NF-&(kappa)B network with both protein and RNA mediated interactions.

Mol Cell Proteomics. 2016 Sep 8;

Authors: Banks CA, Boanca G, Lee ZT, Eubanks CG, Hattem GL, Peak A, Weems LE, Conkright JJ, Florens L, Washburn MP

Abstract
The NF-κB family of transcription factors is pivotal in controlling cellular responses to environmental stresses; abnormal NF-κB signaling features in many autoimmune diseases and cancers. Several components of the NF-κB signaling pathway have been reported to interact with the protein TNIP2 (also known as ABIN2), and TNIP2 can both positively and negatively regulate NF-κB- dependent transcription of target genes. However, the function of TNIP2 remains elusive and the cellular machinery associating with TNIP2 has not been systematically defined. Here we first used a broad MudPIT/Halo AP-MS approach to map the network of proteins associated with the NF-κB transcription factors, and establish TNIP2 as an NF-κB network hub protein. We then combined AP-MS with biochemical approaches in a more focused study of truncated and mutated forms of TNIP2 to map protein associations with distinct regions of TNIP2. NF-κB interacted with the N-terminal region of TNIP2. A central region of TNIP2 interacted with the endosomal sorting complex ESCRT-I via its TSG101 subunit, a protein essential for HIV-1 budding, and a single point mutant in TNIP2 disrupted this interaction. The major gene ontology category for TNIP2 associated proteins was mRNA metabolism, and several of these associations, like KHDRBS1, were lost upon depletion of RNA. Given the major association of TNIP2 with mRNA metabolism proteins, we analyzed the RNA content of affinity purified TNIP2 using RNA-Seq. Surprisingly, a specific limited number of mRNAs was associated with TNIP2. These RNAs were enriched for transcription factor binding, transcription factor co-factor activity, and transcription regulator activity. They included mRNAs of genes in the Sin3A complex, the Mediator complex, JUN, HOXC6, and GATA2. Taken together, our findings suggest an expanded role for TNIP2, establishing a link between TNIP2, cellular transport machinery, and RNA transcript processing.

PMID: 27609421 [PubMed - as supplied by publisher]

Q&A: Gordon Mills on Neomorphs in Cancer.

Cancer Discov. 2016 Sep 8;

Authors:

Abstract
Gordon Mills, MD, PhD, chair of systems biology at The University of Texas MD Anderson Cancer Center in Houston, discusses a third category of genomic aberrations besides oncogene activation or tumor suppressor inactivation: neomorphs, or mutations that rewire cellular signaling in unexpected ways, with important functional consequences.

PMID: 27609219 [PubMed - as supplied by publisher]

Hydrogen peroxide and central redox theory for aerobic life: A tribute to Helmut Sies: Scout, trailblazer, and redox pioneer.

Arch Biochem Biophys. 2016 Apr 1;595:13-8

Authors: Jones DP

Abstract
When Rafael Radi and I wrote about Helmut Sies for the Redox Pioneer series, I was disappointed that the Editor restricted us to the use of "Pioneer" in the title. My view is that Helmut was always ahead of the pioneers: He was a scout discovering paths for exploration and a trailblazer developing strategies and methods for discovery. I have known him for nearly 40 years and greatly enjoyed his collegiality as well as brilliance in scientific scholarship. He made monumental contributions to 20th century physiological chemistry beginning with his first measurement of H2O2 in rat liver. While continuous H2O2 production is dogma today, the concept of H2O2 production in mammalian tissues was largely buried for half a century. He continued this leadership in research on oxidative stress, GSH, selenium, and singlet oxygen, during the timeframe when physiological chemistry and biochemistry transitioned to contemporary 21st century systems biology. His impact has been extensive in medical and health sciences, especially in nutrition, aging, toxicology and cancer. I briefly summarize my interactions with Helmut, stressing our work together on the redox code, a set of principles to link mitochondrial respiration, bioenergetics, H2O2 metabolism, redox signaling and redox proteomics into central redox theory.

PMID: 27095208 [PubMed - indexed for MEDLINE]

A Systems Biology-Based Investigation into the Pharmacological Mechanisms of Sheng-ma-bie-jia-tang Acting on Systemic Lupus Erythematosus by Multi-Level Data Integration.

Sci Rep. 2015;5:16401

Authors: Huang L, Lv Q, Liu F, Shi T, Wen C

Abstract
Sheng-ma-bie-jia-tang (SMBJT) is a Traditional Chinese Medicine (TCM) formula that is widely used for the treatment of Systemic Lupus Erythematosus (SLE) in China. However, molecular mechanism behind this formula remains unknown. Here, we systematically analyzed targets of the ingredients in SMBJT to evaluate its potential molecular mechanism. First, we collected 1,267 targets from our previously published database, the Traditional Chinese Medicine Integrated Database (TCMID). Next, we conducted gene ontology and pathway enrichment analyses for these targets and determined that they were enriched in metabolism (amino acids, fatty acids, etc.) and signaling pathways (chemokines, Toll-like receptors, adipocytokines, etc.). 96 targets, which are known SLE disease proteins, were identified as essential targets and the rest 1,171 targets were defined as common targets of this formula. The essential targets directly interacted with SLE disease proteins. Besides, some common targets also had essential connections to both key targets and SLE disease proteins in enriched signaling pathway, e.g. toll-like receptor signaling pathway. We also found distinct function of essential and common targets in immune system processes. This multi-level approach to deciphering the underlying mechanism of SMBJT treatment of SLE details a new perspective that will further our understanding of TCM formulas.

PMID: 26560501 [PubMed - indexed for MEDLINE]

Bottom-Up Proteomics (2013-2015): Keeping up in the Era of Systems Biology.

Anal Chem. 2016 Jan 5;88(1):95-121

Authors: Mayne J, Ning Z, Zhang X, Starr AE, Chen R, Deeke S, Chiang CK, Xu B, Wen M, Cheng K, Seebun D, Star A, Moore JI, Figeys D

PMID: 26558748 [PubMed - indexed for MEDLINE]

Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?

OMICS. 2015 Nov;19(11):669-87

Authors: Sevimoglu T, Arga KY

Abstract
Computational biology and 'omics' systems sciences are greatly impacting research on common diseases such as cancer. By contrast, dermatology covering an array of skin diseases with high prevalence in society, has received relatively less attention from 'omics' and computational biosciences. We are focusing on psoriasis, a common and debilitating autoimmune disease involving skin and joints. Using computational systems biology and reconstruction, topological, modular, and a novel correlational analyses (based on fold changes) of biological and transcriptional regulatory networks, we analyzed and integrated data from a total of twelve studies from the Gene Expression Omnibus (sample size = 534). Samples represented a comprehensive continuum from lesional and nonlesional skin, as well as bone marrow and dermal mesenchymal stem cells. We identified and propose here a JAK/STAT signaling pathway significant for psoriasis. Importantly, cytokines, interferon-stimulated genes, antimicrobial peptides, among other proteins, were involved in intrinsic parts of the proposed pathway. Several biomarker and therapeutic candidates such as SUB1 are discussed for future experimental studies. The integrative systems biology approach presented here illustrates a comprehensive perspective on the molecular basis of psoriasis. This also attests to the promise of systems biology research in skin diseases, with psoriasis as a systemic component. The present study reports, to the best of our knowledge, the largest set of microarray datasets on psoriasis, to offer new insights into the disease mechanisms with a proposal of a disease pathway. We call for greater computational systems biology research and analyses in dermatology and skin diseases in general.

PMID: 26480058 [PubMed - indexed for MEDLINE]

New perspectives on the mutated NGLY1 enigma.

Med Hypotheses. 2015 Nov;85(5):584-5

Authors: Tickotsky-Moskovitz N

Abstract
The enzyme N-glycanase 1 (NGLY1) is considered a component of the endoplasmic reticulum-associated degradation (ERAD) machinery and clinical manifestations of its dysfunction include global developmental delay, a movement disorder, peripheral neuropathy, liver disorders, microcephaly, diminished reflexes and seizures. Although several mutations in NGLY1 have been identified, the relation between the defected protein and the above described pathologies is yet unknown. We hypothesised that NGLY1 failure to degrade certain proteins may result in their accumulation and overexpression and used a systems biology approach to identify proteins that may be affected by NGLY1 deficiency. Genes that interact with the NGLY1 gene according to BioGRID database of physical and genetic interactions were analysed with STRING Protein-Protein interaction database. Network analysis identified FAF1 (Fas-Associated Factor 1), an apoptosis-potentiating protein, as a possible degradation substrate of NGLY1. Examination of normal tissue microarrays demonstrated that FAF1-to-NGLY1 ratio is maximal (more than 3:1) in skeletal muscle and brain tissues microarrays. This evidence may explain the pathologies in brain and muscle tissues of patients with mutated NGLY1. To test this hypothesis, laboratory studies that will assess if FAF1 protein is overexpressed in tissues of patients with mutated NGLY1 are required.

PMID: 26228302 [PubMed - indexed for MEDLINE]

Integrated systems approach identifies risk regulatory pathways and key regulators in coronary artery disease.

J Mol Med (Berl). 2015 Dec;93(12):1381-90

Authors: Zhang Y, Liu D, Wang L, Wang S, Yu X, Dai E, Liu X, Luo S, Jiang W

Abstract
UNLABELLED: Coronary artery disease (CAD) is the most common type of heart disease. However, the molecular mechanisms of CAD remain elusive. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, inferring risk regulatory pathways is an important step toward elucidating the mechanisms underlying CAD. With advances in high-throughput data, we developed an integrated systems approach to identify CAD risk regulatory pathways and key regulators. Firstly, a CAD-related core subnetwork was identified from a curated transcription factor (TF) and microRNA (miRNA) regulatory network based on a random walk algorithm. Secondly, candidate risk regulatory pathways were extracted from the subnetwork by applying a breadth-first search (BFS) algorithm. Then, risk regulatory pathways were prioritized based on multiple CAD-associated data sources. Finally, we also proposed a new measure to prioritize upstream regulators. We inferred that phosphatase and tensin homolog (PTEN) may be a key regulator in the dysregulation of risk regulatory pathways. This study takes a closer step than the identification of disease subnetworks or modules. From the risk regulatory pathways, we could understand the flow of regulatory information in the initiation and progression of the disease. Our approach helps to uncover its potential etiology.
KEY MESSAGES: We developed an integrated systems approach to identify risk regulatory pathways. We proposed a new measure to prioritize the key regulators in CAD. PTEN may be a key regulator in dysregulation of the risk regulatory pathways.

PMID: 26208504 [PubMed - indexed for MEDLINE]

A systems biology approach for elucidating the interaction of curcumin with Fanconi anemia FANC G protein and the key disease targets of leukemia.

J Recept Signal Transduct Res. 2016 Sep 8;:1-7

Authors: Mahato D, Samanta D, Mukhopadhyay SS, Krishnaraj RN

Abstract
Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of malignancies including acute myeloid leukemia and squamous cell carcinoma. There is a constant search out of new potential therapeutic molecule to combat this disorder. In most cases, patients with FA develop haematological malignancies with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs which can efficiently block the pathways of both these disorders can be an ideal and novel strategy to treat FA. The curcumin, a natural compound obtained from turmeric is an interesting therapeutic molecule as it has been reported in the literature to combat both FA as well as leukemia. However, its complete mechanism is not elucidated. Herein, a systems biology approach for elucidating the therapeutic potential of curcumin against FA and leukemia is investigated by analyzing the computational molecular interactions of curcumin ligand with FANC G of FA and seven other key disease targets of leukemia. The proteins namely DOT1L, farnesyl transferase (FDPS), histone decetylase (EP3000), Polo-like kinase (PLK-2), aurora-like kinase (AUKRB), tyrosine kinase (ABL1), and retinoic acid receptor alpha (RARA) were chosen as disease targets for leukemia and modeled structure of FANC G protein as the disease target for FA. The docking investigations showed that curcumin had a very high binding affinity of -8.1 kcal/mol with FANC G protein. The key disease targets of leukemia namely tyrosine kinase (ABL1), aurora-like kinase (AUKRB), and polo-like kinase (PLK-2) showed that they had the comparable binding affinities of -9.7 k cal/mol, -8.7 k cal/mol, and -8.6 k cal/mol, respectively with curcumin. Further, the percentage similarity scores obtained from PAM50 using EMBOSS MATCHER was shown to provide a clue to understand the structural relationships to an extent and to predict the binding affinity. This investigation shows that curcumin effectively interacts with the disease targets of both FA and leukemia.

PMID: 27608133 [PubMed - as supplied by publisher]

Systems Perspective of Morbillivirus Replication.

J Mol Microbiol Biotechnol. 2016 Sep 9;26(6):389-400

Authors: Kumar N, Barua S, Thachamvally R, Tripathi BN

Abstract
Systems biology refers to system-wide changes in biological components such as RNA/DNA (genomics), protein (proteomics) and lipids (lipidomics). In this review, we provide comprehensive information about morbillivirus replication. Besides discussing the role of individual viral/host proteins in virus replication, we also discuss how systems-level analyses could improve our understanding of morbillivirus replication, host-pathogen interaction, immune response and disease resistance. Finally, we discuss how viroinformatics is likely to provide important insights for understanding genome-genome, genome-protein and protein-protein interactions.

PMID: 27607146 [PubMed - as supplied by publisher]

41st FEBS Congress, Molecular and Systems Biology for a Better Life, Ephesus/Kuşadasi, Turkey, September 3-8, 2016.

FEBS J. 2016 Sep;283 Suppl 1:2-427

Authors:

PMID: 27604825 [PubMed - in process]

Role of Systems Biology in Brain Injury Biomarker Discovery: Neuroproteomics Application.

Methods Mol Biol. 2016;1462:157-74

Authors: Jaber Z, Aouad P, Al Medawar M, Bahmad H, Abou-Abbass H, Ghandour H, Mondello S, Kobeissy F

Abstract
Years of research in the field of neurotrauma have led to the concept of applying systems biology as a tool for biomarker discovery in traumatic brain injury (TBI). Biomarkers may lead to understanding mechanisms of injury and recovery in TBI and can be potential targets for wound healing, recovery, and increased survival with enhanced quality of life. The literature available on neurotrauma studies from both animal and clinical studies has provided rich insight on the molecular pathways and complex networks of TBI, elucidating the proteomics of this disease for the discovery of biomarkers. With such a plethora of information available, the data from the studies require databases with tools to analyze and infer new patterns and associations. The role of different systems biology tools and their use in biomarker discovery in TBI are discussed in this chapter.

PMID: 27604718 [PubMed - in process]

Application of Systems Biology to Neuroproteomics: The Path to Enhanced Theranostics in Traumatic Brain Injury.

Methods Mol Biol. 2016;1462:139-55

Authors: Jaber Z, Aouad P, Al Medawar M, Bahmad H, Abou-Abbass H, Kobeissy F

Abstract
The application of systems biology tools in analyzing heterogeneous data from multiple sources has become a necessity, especially in biomarker discovery. Such tools were developed with several approaches to address different types of research questions and hypotheses. In the field of neurotrauma and traumatic brain injury (TBI), three distinct approaches have been used so far as systems biology tools, namely functional group categorization, pathway analysis, and protein-protein interaction (PPI) networks. The databases allow for query of the system to identify candidate targets which can be further studied to elucidate potential downstream biomarkers indicative of disease progression, severity, and improvement. The various systems biology tools, databases, and strategies that can be implemented on available TBI data in neuroproteomic studies are discussed in this chapter.

PMID: 27604717 [PubMed - in process]

Genome-wide protein-protein interactions and protein function exploration in cyanobacteria.

Sci Rep. 2015;5:15519

Authors: Lv Q, Ma W, Liu H, Li J, Wang H, Lu F, Zhao C, Shi T

Abstract
Genome-wide network analysis is well implemented to study proteins of unknown function. Here, we effectively explored protein functions and the biological mechanism based on inferred high confident protein-protein interaction (PPI) network in cyanobacteria. We integrated data from seven different sources and predicted 1,997 PPIs, which were evaluated by experiments in molecular mechanism, text mining of literatures in proved direct/indirect evidences, and "interologs" in conservation. Combined the predicted PPIs with known PPIs, we obtained 4,715 no-redundant PPIs (involving 3,231 proteins covering over 90% of genome) to generate the PPI network. Based on the PPI network, terms in Gene ontology (GO) were assigned to function-unknown proteins. Functional modules were identified by dissecting the PPI network into sub-networks and analyzing pathway enrichment, with which we investigated novel function of underlying proteins in protein complexes and pathways. Examples of photosynthesis and DNA repair indicate that the network approach is a powerful tool in protein function analysis. Overall, this systems biology approach provides a new insight into posterior functional analysis of PPIs in cyanobacteria.

PMID: 26490033 [PubMed - indexed for MEDLINE]