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Biology subjects

Wilkinson, M. D.

Publications and source records attributed to Wilkinson, M. D..

8 recordsLinked to original sources

FAIR Header Reference genome: A TRUSTworthy standard

The lack of interoperable data standards among reference genome data-sharing platforms inhibits cross-platform analysis while increasing the risk of data provenance loss. Here, we describe the FAIR-bioHeaders Reference genome (FHR), a metadata standard guided by the principles of Findability, Accessibility, Interoperability, and Reuse (FAIR) in addition to the principles of Transparency, Responsibility, User focus, Sustainability, and Technology (TRUST). The objective of FHR is to provide an extensive set of data serialisation methods and minimum data field requirements while still maintaining extensibility, flexibility, and expressivity in an increasingly decentralised genomic data ecosystem. The effort needed to implement FHR is low; FHRs design philosophy ensures easy implementation while retaining the benefits gained from recording both machine and human-readable provenance.

bioinformatics↗

Perturbations of the AMI1 IAM-amidohydrolase expression trigger plant stress responses in Arabidopsis thaliana

The evolutionary success of plants relies to a large extent on their extraordinary ability to adapt to changes in their environment. These adaptations require that plants balance their growth with their stress responses. Plant hormones are crucial mediators orchestrating the underlying adaptive processes. However, whether and how the growth-related hormone auxin and the stress-related hormones jasmonic acid (JA), salicylic acid, and abscisic acid (ABA) are coordinated remains largely elusive. Here, we analyze the physiological role of AMIDASE 1 (AMI1) in plant growth and its possible connection to plant adaptations to abiotic stresses. AMI1 contributes to cellular auxin homeostasis by catalyzing the conversion of indole-acetamide into the major plant auxin indole-3-acetic acid. Functional impairment of AMI1 increases the plants stress status rendering mutant plants more susceptible to abiotic stresses. Transcriptomic analysis of ami1 mutants disclosed the reprogramming of a considerable number of stress-related genes, including JA and ABA biosynthesis genes. The ami1 mutants exhibit only moderately repressed growth, but an enhanced ABA accumulation, which suggests a role for AMI1 in the crosstalk between auxin and ABA. Altogether, our results suggest that AMI1 is involved in coordinating the trade-off between plant growth and stress responses, balancing auxin with ABA homeostasis. HIGHLIGHTThe IAM amidohydrolase AMI1 catalyzes the conversion of IAM into IAA in vivo. Expression of AMI1 is specifically repressed by osmotic stress conditions, which triggers ABA biosynthesis through the induction of NCED3, thereby linking auxin homeostasis with plant stress responses.

plant biology↗

Predicting microbiomes through a deep latent space

MotivationMicrobial communities influence their environment by modifying the availability of compounds such as nutrients or chemical elicitors. Knowing the microbial composition of a site is therefore relevant to improving productivity or health. However, sequencing facilities are not always available, or may be prohibitively expensive in some cases. Thus, it would be desirable to computationally predict the microbial composition from more accessible, easily-measured features. ResultsIntegrating Deep Learning techniques with microbiome data, we propose an artificial neural network architecture based on heterogeneous autoencoders to condense the long vector of microbial abundance values into a deep latent space representation. Then, we design a model to predict the deep latent space and, consequently, to predict the complete microbial composition using environmental features as input. The performance of our system is examined using the rhizosphere microbiome of Maize. We reconstruct the microbial composition (717 taxa) from the deep latent space (10 values) with high fidelity ({inverted question}0.9 Pearson correlation). We then successfully predict microbial composition from environmental variables such as plant age, temperature or precipitation (0.73 Pearson correlation, 0.42 Bray-Curtis). We extend this to predict microbiome composition under hypothetical scenarios, such as future climate change conditions. Finally, via transfer learning, we predict microbial composition in a distinct scenario with only a hundred sequences, and distinct environmental features. We propose that our deep latent space may assist microbiome-engineering strategies when technical or financial resources are limited, through predicting current or future microbiome compositions. AvailabilitySoftware, results, and data are available at https://github.com/jorgemf/DeepLatentMicrobiome

bioinformatics↗

Single-molecule nanopore sensing of actin dynamics and drug binding

Actin is a key protein in the dynamic processes within the eukaryotic cell. To date, methods exploring the molecular state of actin are limited to insights gained from structural approaches, providing a snapshot of protein folding, or methods that require chemical modifications compromising actin monomer thermostability. Nanopore sensing permits label-free investigation of native proteins and is ideally suited to study proteins such as actin that require specialised buffers and cofactors. Using nanopores we determined the state of actin at the macromolecular level (filamentous or globular) and in its monomeric form bound to inhibitors. We revealed urea-dependent and voltage-dependent transitional states and observed unfolding process within which sub-populations of transient actin oligomers are visible. We detected, in real-time, drug-binding and filament-growth events at the single-molecule level. This enabled us to calculate binding stoichiometries and to propose a model for protein dynamics using unmodified, native actin molecules, demostrating the promise of nanopores sensing for in-depth understanding of protein folding landscapes and for drug discovery.

biophysics↗

A biosynthetic platform for antimalarial drug discovery

Advances in synthetic biology have enabled production of a variety of compounds using bacteria as a vehicle for complex compound biosynthesis. Violacein, a naturally occurring indole pigment with antibiotic properties, can be biosynthetically engineered in Escherichia coli expressing its non-native synthesis pathway. To explore whether this synthetic biosynthesis platform could be used for drug discovery, here we have screened bacterially-derived violacein against the main causative agent of human malaria, Plasmodium falciparum. We show the antiparasitic activity of bacterially-derived violacein against the P. falciparum 3D7 laboratory reference strain as well as drug-sensitive and resistant patient isolates, confirming the potential utility of this drug as an antimalarial. We then screen a biosynthetic series of violacein derivatives against P. falciparum growth. The demonstrated varied activity of each derivative against asexual parasite growth points to potential for further development of violacein as an antimalarial. Towards defining its mode of action, we show that biosynthetic violacein affects the parasite actin cytoskeleton, resulting in an accumulation of actin signal that is independent of actin polymerization. This activity points to a target that modulates actin behaviour in the cell either in terms of its regulation or its folding. More broadly, our data show that bacterial synthetic biosynthesis is a suitable platform for antimalarial drug discovery with potential applications in high-throughput and cost-effective drug screening with otherwise chemically-intractable natural products.

synthetic biology↗

Evaluating FAIR Maturity Through a Scalable, Automated, Community-Governed Framework

Transparent evaluations of FAIRness are increasingly required by a wide range of stakeholders, from scientists to publishers, funding agencies and policy makers. We propose a scalable, automatable framework to evaluate digital resources that encompasses measurable indicators, open source tools, and participation guidelines, which come together to accommodate domain relevant community-defined FAIR assessments. The components of the framework are: (1) Maturity Indicators - community-authored specifications that delimit a specific automatically-measurable FAIR behavior; (2) Compliance Tests - small Web apps that test digital resources against individual Maturity Indicators; and (3) the Evaluator, a Web application that registers, assembles, and applies community-relevant sets of Compliance Tests against a digital resource, and provides a detailed report about what a machine \"sees\" when it visits that resource. We discuss the technical and social considerations of FAIR assessments, and how this translates to our community-driven infrastructure. We then illustrate how the output of the Evaluator tool can serve as a roadmap to assist data stewards to incrementally and realistically improve the FAIRness of their resources.

bioinformatics↗

Evaluating FAIR-Compliance Through an Objective, Automated, Community-Governed Framework

With the increased adoption of the FAIR Principles, a wide range of stakeholders, from scientists to publishers, funding agencies and policy makers, are seeking ways to transparently evaluate resource FAIRness. We describe the FAIR Evaluator, a software infrastructure to register and execute tests of compliance with the recently published FAIR Metrics. The Evaluator enables digital resources to be assessed objectively and transparently. We illustrate its application to three widely used generalist repositories - Dataverse, Dryad, and Zenodo - and report their feedback. Evaluations allow communities to select relevant Metric subsets to deliver FAIRness measurements in diverse and specialized applications. Evaluations are executed in a semi-automated manner through Web Forms filled-in by a user, or through a JSON-based API. A comparison of manual vs automated evaluation reveals that automated evaluations are generally stricter, resulting in lower, though more accurate, FAIRness scores. Finally, we highlight the need for enhanced infrastructure such as standards registries, like FAIRsharing, as well as additional community involvement in domain-specific data infrastructure creation.

scientific communication and education↗

A design framework and exemplar metrics for FAIRness

\"FAIRness\" - the degree to which a digital resource is Findable, Accessible, Interoperable, and Reusable - is aspirational, yet the means of reaching it may be defined by increased adherence to measurable indicators. We report on the production of a core set of semi-quantitative metrics having universal applicability for the evaluation of FAIRness, and a rubric within which additional metrics can be generated by the community. This effort is the output from a stakeholder-representative group, founded by a core of FAIR principles co-authors and drivers. We now seek input from the community to more broadly discuss their merit.

scientific communication and education↗