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Over the past years, NGS has become a crucial workhorse for open-view pathogen diagnostics.
Yet, long turnaround times result from using massively parallel high-throughput technologies as the analysis can only be performed after sequencing has finished. The interpretation of results can further be challenged by contaminations, clinically irrelevant sequences, and the sheer amount and complexity of the data.
We implemented PathoLive, a real-time diagnostics pipeline for the detection of pathogens from clinical samples hours before sequencing has finished.
Based on real-time alignment with HiLive2, mappings are scored with respect to common contaminations, low-entropy areas, and sequences of widespread, non-pathogenic organisms.
The results are visualized using an interactive taxonomic tree that provides an easily interpretable overview of the relevance of hits. For a human plasma sample that was spiked in vitro with six pathogenic viruses, all agents were clearly detected after only 40 of 200 sequencing cycles.
For a real-world sample from Sudan, the results correctly indicated the presence of Crimean-Congo hemorrhagic fever virus. In a second real-world dataset from the 2019 SARS-CoV-2 outbreak in Wuhan, we found the presence of a SARS coronavirus as the most relevant hit without the novel virus reference genome being included in the database.
For all samples, clinically irrelevant hits were correctly de-emphasized.
Our approach is valuable to obtain fast and accurate NGS-based pathogen identifications and correctly prioritize and visualize them based on their clinical significance: PathoLive is open source and available on GitLab and BioConda.
Integrated assessment models (IAMs) form a prime tool in informing about climate mitigation strategies. Diagnostic indicators that allow comparison across these models can help describe and explain differences in model projections. This increases transparency and comparability. Earlier, the IAM community has developed an approach to diagnose models (Kriegler (2015 Technol. Forecast. Soc. Change 90 45–61)). Here we build on this, by proposing a selected set of well-defined indicators as a community standard, to systematically and routinely assess IAM behaviour, similar to metrics used for other modeling communities such as climate models. These indicators are the relative abatement index, emission reduction type index, inertia timescale, fossil fuel reduction, transformation index and cost per abatement value. We apply the approach to 17 IAMs, assessing both older as well as their latest versions, as applied in the IPCC 6th Assessment Report. The study shows that the approach can be easily applied and used to indentify key differences between models and model versions. Moreover, we demonstrate that this comparison helps to link model behavior to model characteristics and assumptions. We show that together, the set of six indicators can provide useful indication of the main traits of the model and can roughly indicate the general model behavior. The results also show that there is often a considerable spread across the models. Interestingly, the diagnostic values often change for different model versions, but there does not seem to be a distinct trend.
Different upper tail indicators exist to characterize heavy tail phenomena, but no comparative study has been carried out so far. We evaluate the shape parameter (GEV), obesity index, Gini index and upper tail ratio (UTR) against a novel benchmark of tail heaviness - the surprise factor. Sensitivity analyses to sample size and changes in scale-to-location ratio are carried out in bootstrap experiments. The UTR replicates the surprise factor best but is most uncertain and only comparable between records of similar length. For samples with symmetric Lorenz curves, shape parameter, obesity and Gini indices provide consistent indications. For asymmetric Lorenz curves, however, the first two tend to overestimate, whereas Gini index tends to underestimate tail heaviness. We suggest the use of a combination of shape parameter, obesity and Gini index to characterize tail heaviness. These indicators should be supported with calculation of the Lorenz asymmetry coefficients and interpreted with caution.