Navigating freely-available software tools for metabolomics analysis

Introduction

The field of metabolomics has expanded greatly over the past two decades, both as an experimental science with applications in many areas, as well as in regards to data standards and bioinformatics software tools. The diversity of experimental designs and instrumental technologies used for metabolomics has led to the need for distinct data analysis methods and the development of many software tools.

Objectives

To compile a comprehensive list of the most widely used freely available software and tools that are used primarily in metabolomics.

Methods

The most widely used tools were selected for inclusion in the review by either ≥ 50 citations on Web of Science (as of 08/09/16) or the use of the tool being reported in the recent Metabolomics Society survey. Tools were then categorised by the type of instrumental data (i.e. LC–MS, GC–MS or NMR) and the functionality (i.e. pre- and post-processing, statistical analysis, workflow and other functions) they are designed for.

Results

A comprehensive list of the most used tools was compiled. Each tool is discussed within the context of its application domain and in relation to comparable tools of the same domain. An extended list including additional tools is available at https://github.com/RASpicer/MetabolomicsTools which is classified and searchable via a simple controlled vocabulary.

Conclusion

This review presents the most widely used tools for metabolomics analysis, categorised based on their main functionality. As future work, we suggest a direct comparison of tools’ abilities to perform specific data analysis tasks e.g. peak picking.

     

Aptamer-based electrochemical biosensor by using Au-Pt nanoparticles,carbon nanotubes and acriflavine platform

Herein, an ultrasensitive electrochemical aptasensor for quantitative detection of bisphenol A (BPA) was fabricated based on a novel signal amplification strategy. This aptasensor was developed by electrodeposition of gold-platinum nanoparticles (Au-PtNPs) on glassy carbon (GC) electrode modified with acid-oxidized carbon nanotubes (CNTs-COOH). In this protocol, acriflavine (ACF) was covalently immobilized at the surface of glassy carbon electrode modified with Au-PtNPs/CNTs-COOH nanocomposite. Attachment of BPA-aptamer at the surface of modified electrode was performed through the formation of phosphoramidate bonds between the amino group of ACF and phosphate group of the aptamer at 5′end. By interaction of BPA with the aptamer, the conformational of aptamer was changed which lead to retarding the interfacial electron transfer of ACF as a probe. Sensitive quantitative detection of BPA was carried out by monitoring the decrease of differential pulse voltammetric (DPV) responses of ACF peak current with increasing the BPA concentration. The resultant aptasensor exhibited good specificity, stability and reproducibility, indicating that the present strategy was promising for broad potential application.     

Bacillus thuringiensis: a successful insecticide with new environmental features and tidings

Bacillus thuringiensis (Bt) is known as the most successful microbial insecticide against different orders of insect pests in agriculture and medicine. Moreover, Bt toxin genes also have been efficiently used to enhance resistance to insect pests in genetically modified crops. In light of the scientific advantages of new molecular biology technologies, recently, some other new potentials of Bt have been explored. These new environmental features include the toxicity against nematodes, mites, and ticks, antagonistic effects against plant and animal pathogenic bacteria and fungi, plant growth-promoting activities (PGPR), bioremediation of different heavy metals and other pollutants, biosynthesis of metal nanoparticles, production of polyhydroxyalkanoate biopolymer, and anticancer activities (due to parasporins). This review comprehensively describes recent advances in the Bt whole-genome studies, the last updated known Bt toxins and their functions, and application of cry genes in plant genetic engineering. Moreover, the review thoroughly describes the new features of Bt which make it a suitable cell factory that might be used for production of different novel valuable bioproducts.

     

Nutritional status,essential oil changes and water-use efficiency of rose geranium in response to arbuscular mycorrhizal fungi and water deficiency stress

Stress induced by water deficit is considered to be a global problem and one of the most important factors limiting crop production in arid and semi-arid regions of the world. Application of certain microorganisms, including arbuscular mycorrhizal fungi (AMF), is considered to be an effective and sustainable strategy to mitigate the problem. A pot experiment was conducted in the field (from Feb. to Sep. in 2013–2014 in Isfahan, Iran) to assess the effectiveness of AMF inoculation on changes in biomass, essential oils, nutrient uptake and water-use efficiency of rose geranium (Pelargonium graveolens L.) experiencing stress induced by a deficit of water. The experiment was planned as a factorial experiment, using a completely randomized design, with two factors, including four AMF inoculation (non-mycorrhizal, Rhizophagus intraradices and Funneliformis mosseae inoculated, and the combination of both species) and three irrigation levels including well-watered (WW), moderate water deficiency (MWD) and severe water deficiency (SWD). The results indicated the occurrence of an adverse effect of water deficit on plant total biomass; however, AMF inoculation positively increased plant biomass compared to the non-inoculated ones under three irrigation levels. MWD condition resulted in higher essential oil (EO) content (12.4 %), water-use efficiency (WUE) (29.5 %) and glomalin-related soil proteins (GRSP) (19.1 %) in the plants compared to WW condition. Furthermore, all AMF inoculation improved EO content by at least 12 k%. The results also showed that severe water deficiency adversely affected the uptake of most nutrients by plants especially in non-inoculated plants. The results also revealed that, although EO production was under the control of irrigation regime, nutrient uptake was critically dependent on an association with mycorrhizae. Notwithstanding the fact that rose geranium can tolerate moderate drought stress, the high responsiveness of rose geranium to AMF under water deficiency stress confirms the key role of AMF in facilitating the production of this valuable crop in harsh environments. Dual infection of rose geranium with two AMF species could also synergistically affect biomass, essential oil content and mineral elements absorption.     

Tissue engineering: Dentin – pulp complex regeneration approaches (A review)

Dental pulp is a highly specialized tissue that preserves teeth. It is important to maintain the capabilities of dental pulp before a pulpectomy by creating a local restoration of the dentin-pulp complex from residual dental pulp. The articles identified were selected by two reviewers based on entry and exit criteria. All relevant articles indexed in PubMed, Springer, Science Direct, and Scopus with no limitations from 1961 to 2016 were searched. Factors investigated in the selected articles included the following key words: Dentin-Pulp Complex, Regeneration, Tissue Engineering, Scaffold, Stem Cell, and Growth Factors. Of the 233 abstracts retrieved, the papers which were selected had evaluated the clinical aspects of the application of dentin-pulp regeneration. Generally, this study has introduced a new approach to provoke the regeneration of the dentin-pulp complex after a pulpectomy, so that exogenous growth factors and the scaffold are able to induce cells and blood vessels from the residual dental pulp in the tooth root canal. This study further presents a new strategy for local regeneration therapy of the dentin-pulp complex. This review summarizes the current knowledge of the potential beneficial effects derived from the interaction of dental materials with the dentin-pulp complex as well as potential future developments in this exciting field.     

The interaction of beta-lactoglobulin with ciprofloxacin and kanamycin; a spectroscopic and molecular modeling approach

A vast research has been conducted to find suitable and safe carriers for vital and pH-sensitive drugs including antibiotics. This article reports the use of easily accessible and abundant purified beta-lactoglobulin (β-LG) protein as the potential carrier of widely used Kanamycin (Kana) and Ciprofloxacin (Cip) antibiotics. Spectroscopic techniques (Fluorescence, UV–vis, Circular Dichroism) combined with molecular docking were used to determine the binding mechanism of these drugs. Fluorescence studies showed moderate binding affinity with the calculated binding constants K_Cip = 60.1 (±0.2)?×?10³ M^?1 and K_kana = 2.5 (±0.6)?×?10³ M^?1 with the order of Cip > Kana. Results of UV–vis were consistent with fluorescence measurements and demonstrated a stronger complexation for Cip rather than Kana. The secondary structure of β-LG was preserved upon interaction with Kana; however, a reduction in β-sheet content from 39.1 to 31.9% was convoyed with an increase in α-helix from 12.8 to 20.5% due to complexation of Cip. Molecular docking studies demonstrated that preferred binding sites of these drugs are not the same and several amino acids are involved in stabilizing the interaction. Based on the achieved results, Kana and Cip can spontaneously bind to β-LG and this protein may serve as their transport vehicle.     

2,2′- bipyridine coplanar with coordination square of Pd(II) nonyldithiocarbamato antitumor complex interacting with DNA in two distinct steps

Cisplatin is one of the most effective chemotherapy drugs, and has been widely employed for more than four decades in the treatment of different forms of human tumors. In recent years, various examples of metal complex-based compounds have been used for medicinal purposes. In this context, the novel palladium(II) complex, [Pd(non-dtc)(bpy)]NO₃, (non-dtc = nonyldithiocarbamate and bpy = 2,2′- bipyridine) has been synthesized and characterized by means of elemental analysis, conductivity measurements, FT-IR, ¹H NMR, ¹³C NMR, and electronic spectroscopy studies. The 50% cytotoxic concentrations (Ic₅₀) of this Pd(II) complex (0.53 mM) and cisplatin (154 mM) against human cell tumor line (K562) indicates its interaction with DNA of cancer cell at quite low concentration. Thus, binding characteristics of this compound to calf thymus DNA (CT-DNA) has been investigated by UV–vis absorption spectroscopy and fluorescence spectra. The exciting observation of this work in the UV–visible studies was that the Pd(II) complex exhibit two or more types of interaction with CT-DNA. Such properties have rarely been observed in the literature. This complex cooperatively binds with DNA and denatures it too. Fluorescence studies proved the intercalation mode of binding and the other modes seems to be hydrophobic and electrostatic interactions. Binding parameters and thermodynamics of the interaction with CT-DNA are also described. Finally, multifunctional interactions of [Pd(non-dtc)(bpy)]NO₃ make it suitable to interact with DNA of cancer cell at quite low concentration and if it is used as anticancer agent, very low doses will be needed which may have fewer side effects.     

α-Bisabolol inhibits <Emphasis Type="Italic">Aspergillus fumigatus</Emphasis> Af239 growth via affecting microsomal ∆<Superscript>24</Superscript>-sterol methyltransferase as a crucial enzyme in ergosterol biosynthesis pathway

Finding new compounds with antifungal properties is an important task due to the side effects of common antifungal drugs and emerging antifungal resistance in fungal strains. ?²⁴-sterol methyltransferase (24-SMT) is a crucial enzyme that plays important roles in fungal ergosterol biosynthesis pathway and is not found in humans. In the present study, the effects of α-bisabolol on Aspergillus fumigatus Af239 growth and ergosterol synthesis on the base of 24-SMT enzyme activity were studied; in addition, the expression of erg6, the gene encoded 24-SMT, was considered. To our knowledge, this is the first report demonstrating that α-bisabolol inhibits A. fumigatus growth specifically via suppressing fungal 24-SMT. Since this enzyme is a specific fungal enzyme not reported to exist in mammalian cells, α-bisabolol may serve as a lead compound in the development of new antifungal drugs. Fungi were cultured in presence of serial concentrations of α-bisabolol (0.281–9 mM) for 3 days at 35?°C. Mycelia dry weight was determined as an index of fungal growth and ergosterol content was assessed. Microsomal 24-SMT activity was assayed in presence of α-bisabolol as an inhibitor, lanosterol as a substrate and [methyl-H³] AdoMet (S-Adenosyl methionin). In addition, the expression of erg 6 gene (24-SMT encoding gene) was determined after treatments with various concentrations of α-bisabolol. Our results demonstrated that α-bisabolol strongly inhibited A. fumigatus growth (35.53–77.17%) and ergosterol synthesis (26.31–73.77%) dose-dependently and suppressed the expression of erg 6 gene by 76.14% at the highest concentration of 9 mM. α-bisabolol inhibited the activity of 24-SMT by 99% at the concentration of 5 mM. Taken together, these results provides an evidence for the first time that α-bisabolol inhibits A. fumigatus Af239 growth via affecting microsomal ?²⁴-sterol methyltransferase as a crucial enzyme in ergosterol biosynthetic pathway.     

Agronomic Evaluation of Camelina (<Emphasis Type="Italic">Camelina sativa</Emphasis> L. Crantz) Cultivars for Biodiesel Feedstock

Recent interest in renewable energy sources and the need to diversify cropping systems have triggered research interest in camelina (Camelina sativa L. Crantz). Camelina is well adapted to the temperate dryland climates and can be used as an energy crop. But information on agronomic evaluation of camelina cultivars for biodiesel feedstock are limited. The objective of this study was to evaluate six spring camelina cultivars (cv. Blaine Creek, Calena, Ligena, Pronghorn, Shoshone, and Suneson) on seed yield, oil concentration, and oil yield. The study was carried out from 2013 to 2015 at three locations (Havre, Moccasin, and Pendroy, MT). Over locations and years, mean seed yield differences among cultivars were significant (P < 0.05). The mean seed yield for cultivars ranging from 1295 kg ha^?1 (Suneson) to 1420 kg ha^?1 (Ligena). Ligena and Calena showed a combination of good seed yield performance and stability across environments. Environmental means for seed yield differences were substantial compared with cultivar means. The location Havre produced 45 and 32% more mean seed yield than Pendroy and Moccasin, respectively. There was no significant difference among cultivars in oil concentration and oil yield. The absence of variations in oil concentration and oil yield differences among these cultivars could indicate the need for further research to improve these qualities essential for biodiesel.