scholarly journals Strainberry: automated strain separation in low-complexity metagenomes using long reads

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Riccardo Vicedomini ◽  
Christopher Quince ◽  
Aaron E. Darling ◽  
Rayan Chikhi

AbstractHigh-throughput short-read metagenomics has enabled large-scale species-level analysis and functional characterization of microbial communities. Microbiomes often contain multiple strains of the same species, and different strains have been shown to have important differences in their functional roles. Recent advances on long-read based methods enabled accurate assembly of bacterial genomes from complex microbiomes and an as-yet-unrealized opportunity to resolve strains. Here we present Strainberry, a metagenome assembly pipeline that performs strain separation in single-sample low-complexity metagenomes and that relies uniquely on long-read data. We benchmarked Strainberry on mock communities for which it produces strain-resolved assemblies with near-complete reference coverage and 99.9% base accuracy. We also applied Strainberry on real datasets for which it improved assemblies generating 20-118% additional genomic material than conventional metagenome assemblies on individual strain genomes. We show that Strainberry is also able to refine microbial diversity in a complex microbiome, with complete separation of strain genomes. We anticipate this work to be a starting point for further methodological improvements on strain-resolved metagenome assembly in environments of higher complexities.

2021 ◽  
Author(s):  
R. Vicedomini ◽  
C. Quince ◽  
A. E. Darling ◽  
R. Chikhi

AbstractHigh-throughput short-read metagenomics has enabled large-scale species-level analysis and functional characterization of microbial communities. Microbiomes often contain multiple strains of the same species, and different strains have been shown to have important differences in their functional roles. Despite this, strain-level resolution from metagenomic sequencing remains challenging. Recent advances on long-read based methods enabled accurate assembly of bacterial genomes from complex microbiomes and an as-yet-unrealized opportunity to resolve strains. Here we present Strainberry, a metagenome assembly method that performs strain separation in single-sample low-complexity metagenomes and that relies uniquely on long-read data. We benchmarked Strainberry on mock communities and showed it consistently produces strain-resolved assemblies with near-complete reference coverage and 99.9% base accuracy. We also applied Strainberry on real datasets for which it improved assemblies generating 27-89% additional genomic material than conventional metagenome assemblies on individual strain genomes. Our results hence demonstrate that strain separation is possible in low-complexity microbiomes using a single regular long read dataset. We show that Strainberry is also able to refine microbial diversity in a complex microbiome, with complete separation of strain genomes. We anticipate this work to be a starting point for further methodological improvements aiming to provide better strain-resolved metagenome assemblies in environments of higher complexities.


2019 ◽  
Vol 22 (5) ◽  
pp. 346-354
Author(s):  
Yan A. Ivanenkov ◽  
Renat S. Yamidanov ◽  
Ilya A. Osterman ◽  
Petr V. Sergiev ◽  
Vladimir A. Aladinskiy ◽  
...  

Aim and Objective: Antibiotic resistance is a serious constraint to the development of new effective antibacterials. Therefore, the discovery of the new antibacterials remains one of the main challenges in modern medicinal chemistry. This study was undertaken to identify novel molecules with antibacterial activity. Materials and Methods: Using our unique double-reporter system, in-house large-scale HTS campaign was conducted for the identification of antibacterial potency of small-molecule compounds. The construction allows us to visually assess the underlying mechanism of action. After the initial HTS and rescreen procedure, luciferase assay, C14-test, determination of MIC value and PrestoBlue test were carried out. Results: HTS rounds and rescreen campaign have revealed the antibacterial activity of a series of Nsubstituted triazolo-azetidines and their isosteric derivatives that has not been reported previously. Primary hit-molecule demonstrated a MIC value of 12.5 µg/mL against E. coli Δ tolC with signs of translation blockage and no SOS-response. Translation inhibition (26%, luciferase assay) was achieved at high concentrations up to 160 µg/mL, while no activity was found using C14-test. The compound did not demonstrate cytotoxicity in the PrestoBlue assay against a panel of eukaryotic cells. Within a series of direct structural analogues bearing the same or bioisosteric scaffold, compound 2 was found to have an improved antibacterial potency (MIC=6.25 µg/mL) close to Erythromycin (MIC=2.5-5 µg/mL) against the same strain. In contrast to the parent hit, this compound was more active and selective, and provided a robust IP position. Conclusion: N-substituted triazolo-azetidine scaffold may be used as a versatile starting point for the development of novel active and selective antibacterial compounds.


Urban Science ◽  
2021 ◽  
Vol 5 (2) ◽  
pp. 42
Author(s):  
Dolores Brandis García

Since the late 20th century major, European cities have exhibited large projects driven by neoliberal urban planning policies whose aim is to enhance their position on the global market. By locating these projects in central city areas, they also heighten and reinforce their privileged situation within the city as a whole, thus contributing to deepening the centre–periphery rift. The starting point for this study is the significance and scope of large projects in metropolitan cities’ urban planning agendas since the final decade of the 20th century. The aim of this article is to demonstrate the correlation between the various opposing conservative and progressive urban policies, and the projects put forward, for the city of Madrid. A study of documentary sources and the strategies deployed by public and private agents are interpreted in the light of a process during which the city has had a succession of alternating governments defending opposing urban development models. This analysis allows us to conclude that the predominant large-scale projects proposed under conservative policies have contributed to deepening the centre–periphery rift appreciated in the city.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanping Long ◽  
Zhijian Liu ◽  
Jinbu Jia ◽  
Weipeng Mo ◽  
Liang Fang ◽  
...  

AbstractThe broad application of single-cell RNA profiling in plants has been hindered by the prerequisite of protoplasting that requires digesting the cell walls from different types of plant tissues. Here, we present a protoplasting-free approach, flsnRNA-seq, for large-scale full-length RNA profiling at a single-nucleus level in plants using isolated nuclei. Combined with 10x Genomics and Nanopore long-read sequencing, we validate the robustness of this approach in Arabidopsis root cells and the developing endosperm. Sequencing results demonstrate that it allows for uncovering alternative splicing and polyadenylation-related RNA isoform information at the single-cell level, which facilitates characterizing cell identities.


Author(s):  
Rong Ran ◽  
Hayoung Oh

AbstractSparse-aware (SA) detectors have attracted a lot attention due to its significant performance and low-complexity, in particular for large-scale multiple-input multiple-output (MIMO) systems. Similar to the conventional multiuser detectors, the nonlinear or compressive sensing based SA detectors provide the better performance but are not appropriate for the overdetermined multiuser MIMO systems in sense of power and time consumption. The linear SA detector provides a more elegant tradeoff between performance and complexity compared to the nonlinear ones. However, the major limitation of the linear SA detector is that, as the zero-forcing or minimum mean square error detector, it was derived by relaxing the finite-alphabet constraints, and therefore its performance is still sub-optimal. In this paper, we propose a novel SA detector, named single-dimensional search-based SA (SDSB-SA) detector, for overdetermined uplink MIMO systems. The proposed SDSB-SA detector adheres to the finite-alphabet constraints so that it outperforms the conventional linear SA detector, in particular, in high SNR regime. Meanwhile, the proposed detector follows a single-dimensional search manner, so it has a very low computational complexity which is feasible for light-ware Internet of Thing devices for ultra-reliable low-latency communication. Numerical results show that the the proposed SDSB-SA detector provides a relatively better tradeoff between the performance and complexity compared with several existing detectors.


2021 ◽  
Vol 17 (1) ◽  
pp. 145-153
Author(s):  
Federica Violi

By browsing the website of Land Matrix, one can measure the extent of land-related large-scale investments in natural resources (LRINRs) and place it on the world map. At the time of writing, the extent of these investments covers an area equal to the surfaces of Spain and Portugal together – or, for football fans, around 60 million football pitches. These investment operations have often been saluted as instrumental to achieve the developmental needs of host countries and as the necessary private counterpart to state (and interstate) efforts aimed at (sustainable) development goals. Yet, the realities on the ground offer a scenario characterised by severe instances of displacement of indigenous or local communities and environmental disruptions. The starting point of this short essay is that these ‘externalities’ are generated through the legal construct enabling the implementation of these investment operations. As such, this contribution lies neatly in the line of research set forth in the excellent books of Kinnari Bhatt and Jennifer Lander, from the perspective of both the development culture shaping these investment operations and the private–public environment in which these are situated. The essay tries and dialogues with both components, while focusing at a metalevel on the theoretical shifts potentially geared to turn a ‘tale of exclusion’ into a ‘tale of inclusion’.


2006 ◽  
Vol 34 (6) ◽  
pp. 1209-1214 ◽  
Author(s):  
B. Hamberger ◽  
J. Bohlmann

Diterpene resin acids, together with monoterpenes and sesquiterpenes, are the most prominent defence chemicals in conifers. These compounds belong to the large group of structurally diverse terpenoids formed by enzymes known as terpenoid synthases. CYPs (cytochrome P450-dependent mono-oxygenases) can further increase the structural diversity of these terpenoids. While most terpenoids are characterized as specialized or secondary metabolites, some terpenoids, such as the phytohormones GA (gibberellic acid), BRs (brassinosteroids) and ABA (abscisic acid), have essential functions in plant growth and development. To date, very few CYP genes involved in conifer terpenoid metabolism have been functionally characterized and were limited to two systems, yew (Taxus) and loblolly pine (Pinus taeda). The characterized yew CYP genes are involved in taxol diterpene biosynthesis, while the only characterized pine terpenoid CYP gene is part of DRA (diterpene resin acid) biosynthesis. These CYPs from yew and pine are members of two apparently conifer-specific CYP families within the larger CYP85 clan, one of four plant CYP multifamily clans. Other CYP families within the CYP85 clan were characterized from a variety of angiosperms with functions in terpenoid phytohormone metabolism of GA, BR, and ABA. The recent development of EST (expressed sequence tag) and FLcDNA (where FL is full-length) sequence databases and cDNA collections for species of two conifers, spruce (Picea) and pine, allows for the discovery of new terpenoid CYPs in gymnosperms by means of large-scale sequence mining, phylogenetic analysis and functional characterization. Here, we present a snapshot of conifer CYP data mining, discovery of new conifer CYPs in all but one family within the CYP85 clan, and suggestions for their functional characterization. This paper will focus on the discovery of conifer CYPs associated with diterpene metabolism and CYP with possible functions in the formation of GA, BR, and ABA in conifers.


2015 ◽  
Vol 20 (2) ◽  
pp. 128-138 ◽  
Author(s):  
Juan Carlos Pérez Mesa ◽  
Emilio Galdeano-Gómez

Purpose – This purpose of this study is to provide empirical evidence of how cooperation is related to suppliers’ performance, a relationship that is thought to be affected by the type of customer and the extent to which the market is diversified. It analyzes horticultural exporting firms in southeastern Spain, which are the main suppliers of European markets. Together with their primary customers (large-scale retail companies such as Carrefour, Tesco and Aldi), these firms constitute a complex supply network composed of a variety of agents and sales channels. This network will be studied from the perspective of the supplier–supplier relationship that is critical to their survival. Design/methodology/approach – Starting with a detailed description of Europe’s vegetable supply chain, a hierarchical regression is used with an index of cooperation intensity, moderated by retail sales and market concentration. The authors test the hypotheses using panel data on a set of 118 horticultural marketing firms in southeast Spain for the period 2009-2011. Findings – Cooperation strategies are shown to have positive effects on performance (market creation, promotion, quality, training, joint supply purchases and research ventures). Moreover, the retail channel and market diversification are observed to have a positive effect on the relationship between cooperation and the supplier’s performance. They demonstrate that active cooperation strategies have a greater bearing on performance in those firms whose primary customers are retailers. This circumstance provides evidence of the synergies and benefits that may arise when the supplier integrates the retailer in the supply chain, but which do not arise with other types of customers. Research limitations/implications – Although this study refers to a specific sector (fruits and vegetables) and the statistical results are limited, they provide insights that may assist in understanding how other perishable produce-related industries work: such industries share many common features. Practical implications – A more stable relationship between suppliers and retailers in the perishable produce market will render the supply firm more cooperative, competitive and profitable. Increased performance does not arise from the better conditions and improved sales power offered by the customer but instead from the adaptability of the supplier. Likewise, market diversification drives the supply firm toward a cooperative strategy, making it more profitable and competitive. As a practical norm, market diversification alone will not have positive results on performance unless the firm proves capable of enhancing its capacity for cooperation. Social implications – Proper management of the agricultural produce supply chain has repercussions on all of the members of that chain, although special emphasis should be placed on producers and consumers. The availability of food, its quality and its safety depend on management during the production phase. Along these lines, and more specifically for the consumer, this work is relevant because the sector analyzed accounts for 40 per cent of the vegetables consumed in Europe. Originality/value – This article defends the supplier–supplier relationship as the starting point for the analysis of a supply network. In certain sectors, the suppliers’ ability both to solve their clients’ problems and to be profitable is conditioned on maintaining the network and, therefore, the basic focus must center on analyzing their relationships, always including the customer, who has a direct or indirect influence on those relationships. Previous research has not comprehensively addressed this issue, let alone that of a sector with agile and perishable products in which, due to its nature, decision-making about market destinations and sales channels is the order of the day.


2016 ◽  
Vol 21 (10) ◽  
pp. 1042-1053 ◽  
Author(s):  
Clara Stead ◽  
Adam Brown ◽  
Cathryn Adams ◽  
Sarah J. Nickolls ◽  
Gareth Young ◽  
...  

Glycine receptor 3 (GlyRα3) is a ligand-gated ion channel of the cys-loop family that plays a key role in mediating inhibitory neurotransmission and regulation of pain signaling in the dorsal horn. Potentiation of GlyRα3 function is therefore of interest as a putative analgesic mechanism with which to target new therapeutics. However, to date, positive allosteric modulators (PAMs) of this receptor with sufficient selectivity to enable target validation studies have not been described. To address this lack of pharmacological tools, we developed a suite of in vitro assays comprising a high-throughput fluorescent membrane potential screen and a medium-throughput electrophysiology assay using IonFlux HT together with conventional manual patch clamp. Using these assays, we conducted a primary screening campaign and report the structures of hit compounds identified as GlyR PAMs. Our functional characterization data reveal a hit compound with high efficacy relative to current known potentiators and selectivity over GABAAR, another major class of inhibitory neurotransmission receptors of importance to pain. These small-molecule GlyR PAMs have high potential both as early tool compounds to enable pharmacological studies of GlyR inhibitory neurotransmission and as a starting point for the development of potent, selective GlyRα3 PAMs as novel analgesics.


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