PepeSearch: Semantic Data for the Masses.

PLoS One. 2016;11(3):e0151573

Authors: Vega-Gorgojo G, Giese M, Heggestøyl S, Soylu A, Waaler A

Abstract
With the emergence of the Web of Data, there is a need of tools for searching and exploring the growing amount of semantic data. Unfortunately, such tools are scarce and typically require knowledge of SPARQL/RDF. We propose here PepeSearch, a portable tool for searching semantic datasets devised for mainstream users. PepeSearch offers a multi-class search form automatically constructed from a SPARQL endpoint. We have tested PepeSearch with 15 participants searching a Linked Open Data version of the Norwegian Register of Business Enterprises for non-trivial challenges. Retrieval performance was encouragingly high and usability ratings were also very positive, thus suggesting that PepeSearch is effective for searching semantic datasets by mainstream users. We also assessed its portability by configuring PepeSearch to query other SPARQL endpoints.

PMID: 26967899 [PubMed - indexed for MEDLINE]

Antiparallel protocadherin homodimers use distinct affinity- and specificity-mediating regions in cadherin repeats 1-4.

Elife. 2016 Jul 29;5

Authors: Nicoludis JM, Vogt BE, Green AG, Schärfe CP, Marks DS, Gaudet R

Abstract
Protocadherins (Pcdhs) are cell adhesion and signaling proteins used by neurons to develop and maintain neuronal networks, relying on trans homophilic interactions between their extracellular cadherin (EC) repeat domains. We present the structure of the antiparallel EC1-4 homodimer of human PcdhγB3, a member of the γ subfamily of clustered Pcdhs. Structure and sequence comparisons of α, β, and γ clustered Pcdh isoforms illustrate that subfamilies encode specificity in distinct ways through diversification of loop region structure and composition in EC2 and EC3, which contains isoform-specific conservation of primarily polar residues. In contrast, the EC1/EC4 interface comprises hydrophobic interactions that provide non-selective dimerization affinity. Using sequence coevolution analysis, we found evidence for a similar antiparallel EC1-4 interaction in non-clustered Pcdh families. We thus deduce that the EC1-4 antiparallel homodimer is a general interaction strategy that evolved before the divergence of these distinct protocadherin families.

PMID: 27472898 [PubMed - as supplied by publisher]

Deciphering the Duality of Clock and Growth Metabolism in a Cell Autonomous System Using NMR Profiling of the Secretome.

Metabolites. 2016;6(3)

Authors: Sengupta A, Krishnaiah SY, Rhoades S, Growe J, Slaff B, Venkataraman A, Olarerin-George AO, Van Dang C, Hogenesch JB, Weljie AM

Abstract
Oscillations in circadian metabolism are crucial to the well being of organism. Our understanding of metabolic rhythms has been greatly enhanced by recent advances in high-throughput systems biology experimental techniques and data analysis. In an in vitro setting, metabolite rhythms can be measured by time-dependent sampling over an experimental period spanning one or more days at sufficent resolution to elucidate rhythms. We hypothesized that cellular metabolic effects over such a time course would be influenced by both oscillatory and circadian-independent cell metabolic effects. Here we use nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling of mammalian cell culture media of synchronized U2 OS cells containing an intact transcriptional clock. The experiment was conducted over 48 h, typical for circadian biology studies, and samples collected at 2 h resolution to unravel such non-oscillatory effects. Our data suggest specific metabolic activities exist that change continuously over time in this settting and we demonstrate that the non-oscillatory effects are generally monotonic and possible to model with multivariate regression. Deconvolution of such non-circadian persistent changes are of paramount importance to consider while studying circadian metabolic oscillations.

PMID: 27472375 [PubMed - as supplied by publisher]

System-level genome editing in microbes.

Curr Opin Microbiol. 2016 Jul 26;33:113-122

Authors: Csörgő B, Nyerges Á, Pósfai G, Fehér T

Abstract
The release of the first complete microbial genome sequences at the end of the past century opened the way for functional genomics and systems-biology to uncover the genetic basis of various phenotypes. The surge of available sequence data facilitated the development of novel genome editing techniques for system-level analytical studies. Recombineering allowed unprecedented throughput and efficiency in microbial genome editing and the recent discovery and widespread use of RNA-guided endonucleases offered several further perspectives: (i) previously recalcitrant species became editable, (ii) the efficiency of recombineering could be elevated, and as a result (iii) diverse genomic libraries could be generated more effectively. Supporting recombineering by RNA-guided endonucleases has led to success stories in metabolic engineering, but their use for system-level analysis is mostly unexplored. For the full exploitation of opportunities that are offered by the genome editing proficiency, future development of large scale analytical procedures is also vitally needed.

PMID: 27472027 [PubMed - as supplied by publisher]

Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM.

Arterioscler Thromb Vasc Biol. 2016 Jul 28;

Authors: Perisic LM, Rykaczewska U, Razuvaev A, Sabater-Lleal M, Lengquist M, Miller CL, Ericsson I, Röhl S, Kronqvist M, Aldi S, Magné J, Paloschi V, Vesterlund M, Li Y, Jin H, Diez MG, Roy J, Baldassarre D, Veglia F, Humphries SE, de Faire U, Tremoli E, Odeberg J, Vukojevic V, Lehtiö J, Maegdefessel L, Ehrenborg E, Paulsson-Berne G, Hansson G, Lindeman JH, Eriksson P, Quertermous T, Hamsten A, Hedin U

Abstract
OBJECTIVE: Key augmented processes in atherosclerosis have been identified, whereas less is known about downregulated pathways. Here, we applied a systems biology approach to examine suppressed molecular signatures, with the hypothesis that they may provide insight into mechanisms contributing to plaque stability.
APPROACH AND RESULTS: Muscle contraction, muscle development, and actin cytoskeleton were the most downregulated pathways (false discovery rate=6.99e-21, 1.66e-6, 2.54e-10, respectively) in microarrays from human carotid plaques (n=177) versus healthy arteries (n=15). In addition to typical smooth muscle cell (SMC) markers, these pathways also encompassed cytoskeleton-related genes previously not associated with atherosclerosis. SYNPO2, SYNM, LMOD1, PDLIM7, and PLN expression positively correlated to typical SMC markers in plaques (Pearson r>0.6, P<0.0001) and in rat intimal hyperplasia (r>0.8, P<0.0001). By immunohistochemistry, the proteins were expressed in SMCs in normal vessels, but largely absent in human plaques and intimal hyperplasia. Subcellularly, most proteins localized to the cytoskeleton in cultured SMCs and were regulated by active enhancer histone modification H3K27ac by chromatin immunoprecipitation-sequencing. Functionally, the genes were downregulated by PDGFB and IFNg, exposure to shear flow stress, and oxLDL loading. Genetic variants in PDLIM7, PLN, and SYNPO2 loci associated with progression of carotid intima-media thickness in high-risk subjects without symptoms of cardiovascular disease (n=3378). By eQTL, rs11746443 also associated with PDLIM7 expression in plaques. Mechanistically, silencing of PDLIM7 in vitro led to downregulation of SMC markers and disruption of the actin cytoskeleton, decreased cell spreading, and increased proliferation.
CONCLUSIONS: We identified a panel of genes that reflect the altered phenotype of SMCs in vascular disease and could be early sensitive markers of SMC dedifferentiation.

PMID: 27470516 [PubMed - as supplied by publisher]

The Need for Speed-Kinetic Limits of Drug Transporters.

Trends Pharmacol Sci. 2016 Apr;37(4):243-5

Authors: Matsson P, Lundquist P, Artursson P

PMID: 26922253 [PubMed - indexed for MEDLINE]

Systems medicine, personalized health and therapy.

Pharmacogenomics. 2015;16(14):1527-39

Authors: Siest G, Auffray C, Taniguchi N, Ingelman-Sundberg M, Murray H, Visvikis-Siest S, Ansari M, Marc J, Jacobs P, Meyer U, Van Schaik RH, Müller MM, Wevers RA, Simmaco M, Kussmann M, Manolopoulos VG, Alizadeh BZ, Beastall G, Németh G

Abstract
The 7th Santorini Conference was held in Santorini, Greece, and brought together 200 participants from 40 countries in several continents, including Europe, USA but also Japan, Korea, Brazil and South Africa. The attendees had the opportunity to: listen to 60 oral presentations; participate in two lunch symposia; look at 103 posters, which were divided in two groups ('systems medicine and environment' and 'pharmacogenomics and cancer') and attend a dedicated exhibition with six companies. The meeting was organized by the Institut National de la Santé et de la Recherche Médicale (INSERM) U1122; IGE-PCV and by 'Biologie Prospective' with the collaboration of the European Society of Pharmacogenomics and Theranostics (ESPT), under the auspices of international organizations (e.g., International Federation of Clinical Chemistry and Laboratory medicine [IFCC], European Federation of Clinical Chemistry and Laboratory Medicine [EFLM], European Diagnostic Manufacturers Association [EDMA], Federation of European Pharmacological Societies [EPHAR], European Science Foundation [ESF]). The 3 days of the conference stimulated intensive discussions on systems biology and the influence of omics technologies on personalized health. Sixty speakers were invited or selected from early abstracts and gave presentations on the following topics: From systems biology to systems medicine/pharmacology; Omics/translating pharmacogenomics/proteomic biomarkers/metabolomics; Human nutrition and health/personalized medicine. We are summarizing here the main topics and presentations, according to the successive sessions.

PMID: 26401575 [PubMed - indexed for MEDLINE]

Systems biology approach to studying proliferation-dependent prognostic subnetworks in breast cancer.

Sci Rep. 2015;5:12981

Authors: Song Q, Wang H, Bao J, Pullikuth AK, Li KC, Miller LD, Zhou X

Abstract
Tumor proliferative capacity is a major biological correlate of breast tumor metastatic potential. In this paper, we developed a systems approach to investigate associations among gene expression patterns, representative protein-protein interactions, and the potential for clinical metastases, to uncover novel survival-related subnetwork signatures as a function of tumor proliferative potential. Based on the statistical associations between gene expression patterns and patient outcomes, we identified three groups of survival prognostic subnetwork signatures (SPNs) corresponding to three proliferation levels. We discovered 8 SPNs in the high proliferation group, 8 SPNs in the intermediate proliferation group, and 6 SPNs in the low proliferation group. We observed little overlap of SPNs between the three proliferation groups. The enrichment analysis revealed that most SPNs were enriched in distinct signaling pathways and biological processes. The SPNs were validated on other cohorts of patients, and delivered high accuracy in the classification of metastatic vs non-metastatic breast tumors. Our findings indicate that certain biological networks underlying breast cancer metastasis differ in a proliferation-dependent manner. These networks, in combination, may form the basis of highly accurate prognostic classification models and may have clinical utility in guiding therapeutic options for patients.

PMID: 26257336 [PubMed - indexed for MEDLINE]

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Rational selection of predictive pharmacogenomics test for the Fluoropyrimidine/Oxaliplatin based therapy.

Eur Rev Med Pharmacol Sci. 2015 Nov;19(22):4443-54

Authors: Di Francia R, De Lucia L, Di Paolo M, Di Martino S, Del Pup L, De Monaco A, Lleshi A, Berretta M

Abstract
OBJECTIVE: Both Fluoropyrimidine and Oxaliplatin (FluOx) are the most common anticancer drugs used to treat colorectal, ovarian, and gastrointestinal cancers. Nevertheless, the efficacy of FluOx-based therapy is often compromised by the severe risk of neurotoxicity, cardiotoxicity, and gastrointestinal toxicity. Stratification of patients for their individual response to drugs is a promising approach for cancer treatment and cost-effectiveness. Here we evaluate the most recent findings on the most appropriate gene variants related to the toxicity in patients receiving FluOx chemotherapy.
MATERIALS AND METHODS: A systematic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted to identify all clinical studies of any association between DPYD and 5-FU correlated to allelic status of 6 validated polymorphisms in five genes Dihydropyrimidine Dehydrogenase (DPYD), Thymidylate Synthase (TYMS), Glutathione S-Transferase (GSTP1), and DNA-repair genes (ERCC2 and XRCC1).
RESULTS: The stratification of the patients into three genotype profiles group, who are most likely responders to FluOx treatments, provide informations about toxicity and/or resistance before starting therapy. Also, early evaluation cost of panel testing proposed is averaged about €100,00 per sample. The evaluation costs of genotyping before starting treatment could be a good cost-effectiveness strategy.
CONCLUSIONS: Based on the individual genomic profile, the oncologists will have new possibilities, based on the individual genetic profile, to make treatment decisions for their patients and to redefine scheduling and dosage of FluOx-based therapy.

PMID: 26636535 [PubMed - indexed for MEDLINE]

U.S. Medical Eligibility Criteria for Contraceptive Use, 2016.

MMWR Recomm Rep. 2016;65(3):1-103

Authors: Curtis KM, Tepper NK, Jatlaoui TC, Berry-Bibee E, Horton LG, Zapata LB, Simmons KB, Pagano HP, Jamieson DJ, Whiteman MK

Abstract
The 2016 U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) comprises recommendations for the use of specific contraceptive methods by women and men who have certain characteristics or medical conditions. These recommendations for health care providers were updated by CDC after review of the scientific evidence and consultation with national experts who met in Atlanta, Georgia, during August 26-28, 2015. The information in this report updates the 2010 U.S. MEC (CDC. U.S. medical eligibility criteria for contraceptive use, 2010. MMWR 2010:59 [No. RR-4]). Notable updates include the addition of recommendations for women with cystic fibrosis, women with multiple sclerosis, and women receiving certain psychotropic drugs or St. John's wort; revisions to the recommendations for emergency contraception, including the addition of ulipristal acetate; and revisions to the recommendations for postpartum women; women who are breastfeeding; women with known dyslipidemias, migraine headaches, superficial venous disease, gestational trophoblastic disease, sexually transmitted diseases, and human immunodeficiency virus; and women who are receiving antiretroviral therapy. The recommendations in this report are intended to assist health care providers when they counsel women, men, and couples about contraceptive method choice. Although these recommendations are meant to serve as a source of clinical guidance, health care providers should always consider the individual clinical circumstances of each person seeking family planning services. This report is not intended to be a substitute for professional medical advice for individual patients. Persons should seek advice from their health care providers when considering family planning options.

PMID: 27467196 [PubMed - as supplied by publisher]

Acquired Cystic Fibrosis Transmembrane Conductance Regulator Deficiency.

Adv Otorhinolaryngol. 2016;79:78-85

Authors: Cho DY, Woodworth BA

Abstract
In the genetic airway disease cystic fibrosis (CF), deficiency or dysfunction of the cystic fibrosis membrane conductance regulator (CFTR) alters anion transport in respiratory epithelium and consequently disrupts mucociliary clearance. An enriched understanding of the role of CFTR in the maintenance of normal epithelial function has revealed that mild and variable CFTR mutations play a causative role in a number of diseases not classically associated with CF. Furthermore, recent evidence indicates that acquired defects in wild-type CFTR protein processing, endocytic recycling and function can contribute to the pathogenesis of airway diseases, such as chronic obstructive pulmonary disease. In this chapter, we discuss emerging findings implicating acquired CFTR dysfunction in the pathogenesis of chronic rhinosinusitis and propose a new and leading edge approach to future CRS therapy using CFTR potentiators.

PMID: 27466849 [PubMed - as supplied by publisher]

Cystic Fibrosis Sinusitis.

Adv Otorhinolaryngol. 2016;79:29-37

Authors: Le C, McCrary HC, Chang E

Abstract
Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CF transmembrane conductance regulator gene(CFTR) resulting in impaired ion transport. Nearly all people with CF will develop chronic rhino-sinusitis (CRS) and present with the characteristic viscous mucus, impaired mucociliary clearance and chronic inflammation/infection of the sinonasal cavity. While some individuals with CF can appear relatively asymptomatic in terms of their sinus disease, commonly reported symptoms include anosmia, headache, facial pain, nasal obstruction, chronic congestion and nasal discharge. Nasal endoscopy typically reveals mucosal edema, purulent discharge and nasal polyposis. Computed tomography (CT) imaging classically demonstrates the distinguishing findings of sinus hypoplasia or aplasia with generalized opacification, medial bulging of the lateral sinonasal sidewall and a demineralized uncinate process. Current treatment for CF sinusitis includes the use of hypertonic saline, topical and systemic steroids, antibiotics and endoscopic surgery. Research investigating novel therapies designed at targeting the primary defect of CF is showing promise for reversal of CF sinus disease, in addition to potential for disease prevention.

PMID: 27466844 [PubMed - as supplied by publisher]

Differential Diagnosis of Chronic Rhinosinusitis with Nasal Polyps.

Adv Otorhinolaryngol. 2016;79:1-12

Authors: London NR, Reh DD

Abstract
Nasal polyps are semi-translucent mucosal outgrowths of the paranasal sinuses which typically arise in the setting of chronic rhinosinusitis (CRS). Nasal polyps are also associated with asthma, aspirin sensitivity, cystic fibrosis and allergic fungal rhinosinusitis (AFS). The majority of nasal polyps are bilateral and characterized by tissue edema and eosinophil infiltration. Patients with nasal polyps often present with complaints including nasal obstruction, congestion, rhinorrhea or altered sense of smell. The differential diagnosis ranges from benign masses such as schneiderian papilloma, antrochoanal polyp, angiofibroma and encephalocele to malignant neoplasms such as squamous cell carcinoma (SCC), esthesioneuroblastoma, nasal lymphoma and rhabdomyosarcoma. These lesions may have a similar appearance as nasal polyps and particular attention to an alternative diagnosis for nasal polyps should be entertained if the mass is unilateral or congenital in nature. Workup for patients with a unilateral mass should include radiographic imaging, possible biopsy and careful follow-up when appropriate. Here, we review the disease etiology of nasal polyps and describe the approach to the patient with nasal polyps with emphasis on differential diagnosis and workup.

PMID: 27466841 [PubMed - as supplied by publisher]

Lichen secondary metabolite evernic acid as potential quorum sensing inhibitor against Pseudomonas aeruginosa.

World J Microbiol Biotechnol. 2016 Sep;32(9):150

Authors: Gökalsın B, Sesal NC

Abstract
Cystic Fibrosis is a genetic disease and it affects the respiratory and digestive systems. Pseudomonas aeruginosa infections in Cystic Fibrosis are presented as the main cause for high mortality and morbidity rates. Pseudomonas aeruginosa populations can regulate their virulence gene expressions via the bacterial communication system: quorum sensing. Inhibition of quorum sensing by employing quorum sensing inhibitors can leave the bacteria vulnerable. Therefore, determining natural sources to obtain potential quorum sensing inhibitors is essential. Lichens have ethnobotanical value for their medicinal properties and it is possible that their secondary metabolites have quorum sensing inhibitor properties. This study aims to investigate an alternative treatment approach by utilizing lichen secondary metabolite evernic acid to reduce the expressions of Pseudomonas aeruginosa virulence factors by inhibiting quorum sensing. For this purpose, fluorescent monitor strains were utilized for quorum sensing inhibitor screens and quantitative reverse-transcriptase PCR analyses were conducted for comparison. Results indicate that evernic acid is capable of inhibiting Pseudomonas aeruginosa quorum sensing systems.

PMID: 27465850 [PubMed - in process]

Principles of Systems Biology, No. 7.

Cell Syst. 2016 Jul 27;3(1):3-6

Authors:

Abstract
With applications of CRISPR-Cas proteins for probing chromatin dynamics and recording information in a genome, this month's Cell Systems call (Cell Systems 1, 307) highlights a plethora of new techniques.

PMID: 27467241 [PubMed - as supplied by publisher]

Altered protein phosphorylation as a resource for potential AD biomarkers.

Sci Rep. 2016;6:30319

Authors: Henriques AG, Müller T, Oliveira JM, Cova M, da Cruz E Silva CB, da Cruz E Silva OA

Abstract
The amyloidogenic peptide, Aβ, provokes a series of events affecting distinct cellular pathways regulated by protein phosphorylation. Aβ inhibits protein phosphatases in a dose-dependent manner, thus it is expected that the phosphorylation state of specific proteins would be altered in response to Aβ. In fact several Alzheimer's disease related proteins, such as APP and TAU, exhibit pathology associated hyperphosphorylated states. A systems biology approach was adopted and the phosphoproteome, of primary cortical neuronal cells exposed to Aβ, was evaluated. Phosphorylated proteins were recovered and those whose recovery increased or decreased, upon Aβ exposure across experimental sets, were identified. Significant differences were evident for 141 proteins and investigation of their interactors revealed key protein clusters responsive to Aβ treatment. Of these, 73 phosphorylated proteins increased and 68 decreased upon Aβ addition. These phosphorylated proteins represent an important resource of potential AD phospho biomarkers that should be further pursued.

PMID: 27466139 [PubMed - in process]

PCTFPeval: a web tool for benchmarking newly developed algorithms for predicting cooperative transcription factor pairs in yeast.

BMC Bioinformatics. 2015;16 Suppl 18:S2

Authors: Lai FJ, Chang HT, Wu WS

Abstract
BACKGROUND: Computational identification of cooperative transcription factor (TF) pairs helps understand the combinatorial regulation of gene expression in eukaryotic cells. Many advanced algorithms have been proposed to predict cooperative TF pairs in yeast. However, it is still difficult to conduct a comprehensive and objective performance comparison of different algorithms because of lacking sufficient performance indices and adequate overall performance scores. To solve this problem, in our previous study (published in BMC Systems Biology 2014), we adopted/proposed eight performance indices and designed two overall performance scores to compare the performance of 14 existing algorithms for predicting cooperative TF pairs in yeast. Most importantly, our performance comparison framework can be applied to comprehensively and objectively evaluate the performance of a newly developed algorithm. However, to use our framework, researchers have to put a lot of effort to construct it first. To save researchers time and effort, here we develop a web tool to implement our performance comparison framework, featuring fast data processing, a comprehensive performance comparison and an easy-to-use web interface.
RESULTS: The developed tool is called PCTFPeval (Predicted Cooperative TF Pair evaluator), written in PHP and Python programming languages. The friendly web interface allows users to input a list of predicted cooperative TF pairs from their algorithm and select (i) the compared algorithms among the 15 existing algorithms, (ii) the performance indices among the eight existing indices, and (iii) the overall performance scores from two possible choices. The comprehensive performance comparison results are then generated in tens of seconds and shown as both bar charts and tables. The original comparison results of each compared algorithm and each selected performance index can be downloaded as text files for further analyses.
CONCLUSIONS: Allowing users to select eight existing performance indices and 15 existing algorithms for comparison, our web tool benefits researchers who are eager to comprehensively and objectively evaluate the performance of their newly developed algorithm. Thus, our tool greatly expedites the progress in the research of computational identification of cooperative TF pairs.

PMID: 26677932 [PubMed - indexed for MEDLINE]

Sialomes and Mialomes: A Systems-Biology View of Tick Tissues and Tick-Host Interactions.

Trends Parasitol. 2016 Mar;32(3):242-54

Authors: Chmelař J, Kotál J, Karim S, Kopacek P, Francischetti IM, Pedra JH, Kotsyfakis M

Abstract
Tick saliva facilitates tick feeding and infection of the host. Gene expression analysis of tick salivary glands and other tissues involved in host-pathogen interactions has revealed a wide range of bioactive tick proteins. Transcriptomic analysis has been a milestone in the field and has recently been enhanced by next-generation sequencing (NGS). Furthermore, the application of quantitative proteomics to ticks with unknown genomes has provided deeper insights into the molecular mechanisms underlying tick hematophagy, pathogen transmission, and tick-host-pathogen interactions. We review current knowledge on the transcriptomics and proteomics of tick tissues from a systems-biology perspective and discuss future challenges in the field.

PMID: 26520005 [PubMed - indexed for MEDLINE]

Systems Biology for Smart Crops and Agricultural Innovation: Filling the Gaps between Genotype and Phenotype for Complex Traits Linked with Robust Agricultural Productivity and Sustainability.

OMICS. 2015 Oct;19(10):581-601

Authors: Kumar A, Pathak RK, Gupta SM, Gaur VS, Pandey D

Abstract
In recent years, rapid developments in several omics platforms and next generation sequencing technology have generated a huge amount of biological data about plants. Systems biology aims to develop and use well-organized and efficient algorithms, data structure, visualization, and communication tools for the integration of these biological data with the goal of computational modeling and simulation. It studies crop plant systems by systematically perturbing them, checking the gene, protein, and informational pathway responses; integrating these data; and finally, formulating mathematical models that describe the structure of system and its response to individual perturbations. Consequently, systems biology approaches, such as integrative and predictive ones, hold immense potential in understanding of molecular mechanism of agriculturally important complex traits linked to agricultural productivity. This has led to identification of some key genes and proteins involved in networks of pathways involved in input use efficiency, biotic and abiotic stress resistance, photosynthesis efficiency, root, stem and leaf architecture, and nutrient mobilization. The developments in the above fields have made it possible to design smart crops with superior agronomic traits through genetic manipulation of key candidate genes.

PMID: 26484978 [PubMed - indexed for MEDLINE]