Chiropteran types I and II interferon genes inferred from genome sequencing traces by a statistical gene-family assembler

<p>Abstract</p> <p>Background</p> <p>The rate of emergence of human pathogens is steadily increasing; most of these novel agents originate in wildlife. Bats, remarkably, are the natural reservoirs of many of the most pathogenic viruses in humans. There are two bat genome projects currently underway, a circumstance that promises to speed the discovery host factors important in the coevolution of bats with their viruses. These genomes, however, are not yet assembled and one of them will provide only low coverage, making the inference of most genes of immunological interest error-prone. Many more wildlife genome projects are underway and intend to provide only shallow coverage.</p> <p>Results</p> <p>We have developed a statistical method for the assembly of gene families from partial genomes. The method takes full advantage of the quality scores generated by base-calling software, incorporating them into a complete probabilistic error model, to overcome the limitation inherent in the inference of gene family members from partial sequence information. We validated the method by inferring the human IFNA genes from the genome trace archives, and used it to infer 61 type-I interferon genes, and single type-II interferon genes in the bats <it>Pteropus vampyrus </it>and <it>Myotis lucifugus</it>. We confirmed our inferences by direct cloning and sequencing of IFNA, IFNB, IFND, and IFNK in <it>P. vampyrus</it>, and by demonstrating transcription of some of the inferred genes by known interferon-inducing stimuli.</p> <p>Conclusion</p> <p>The statistical trace assembler described here provides a reliable method for extracting information from the many available and forthcoming partial or shallow genome sequencing projects, thereby facilitating the study of a wider variety of organisms with ecological and biomedical significance to humans than would otherwise be possible.</p

Comparison of Small- and Large-Footprint Lidar Characterization of Tropical Forest Aboveground Structure and Biomass: A Case Study From Central Gabon

NASA's Global Ecosystem Dynamic Investigation (GEDI) mission has been designed to measure forest structure using lidar waveforms to sample the earth's vegetation while in orbit aboard the International Space Station. In this paper, we used airborne large-footprint (LF) lidar measurements to simulate GEDI observations from which we retrieved ground elevation, vegetation height, and aboveground biomass (AGB). GEDI-like product accuracy was then assessed by comparing them to similar products derived from airborne small-footprint (SF) lidar measurements. The study focused on tropical forests and used data collected during the NASA and European Space Agency (ESA) AfriSAR ground and airborne campaigns in the Lope National Park in Central Gabon. The measurements covered a gradient of successional stages of forest development with different height, canopy density, and topography. The comparison of the two sensors shows that LF lidar waveforms and simulated waveforms from SF lidar are equivalent in their ability to estimate ground elevation (RMSE = 0.5 m, bias = 0.29 m) and maximum forest height (RMSE = 2.99 m, bias = 0.24 m) over the study area. The difference in the AGB estimated from both lidar instruments at the 1-ha spatial scale is small over the entire study area (RMSE = 6.34 Mg·ha-1, bias = 11.27 Mg·ha-1) and the bias is attributed to the impact of ground slopes greater than 10–20° on the LF lidar measurements of forest height. Our results support the ability of GEDILF lidar to measure the complex structure of humid tropical forests and provide AGB estimates comparable to SF-derived ones

Aboveground biomass density models for NASA's Global Ecosystem Dynamics Investigation (GEDI) lidar mission

NASA's Global Ecosystem Dynamics Investigation (GEDI) is collecting spaceborne full waveform lidar data with a primary science goal of producing accurate estimates of forest aboveground biomass density (AGBD). This paper presents the development of the models used to create GEDI's footprint-level (similar to 25 m) AGBD (GEDI04_A) product, including a description of the datasets used and the procedure for final model selection. The data used to fit our models are from a compilation of globally distributed spatially and temporally coincident field and airborne lidar datasets, whereby we simulated GEDI-like waveforms from airborne lidar to build a calibration database. We used this database to expand the geographic extent of past waveform lidar studies, and divided the globe into four broad strata by Plant Functional Type (PFT) and six geographic regions. GEDI's waveform-to-biomass models take the form of parametric Ordinary Least Squares (OLS) models with simulated Relative Height (RH) metrics as predictor variables. From an exhaustive set of candidate models, we selected the best input predictor variables, and data transformations for each geographic stratum in the GEDI domain to produce a set of comprehensive predictive footprint-level models. We found that model selection frequently favored combinations of RH metrics at the 98th, 90th, 50th, and 10th height above ground-level percentiles (RH98, RH90, RH50, and RH10, respectively), but that inclusion of lower RH metrics (e.g. RH10) did not markedly improve model performance. Second, forced inclusion of RH98 in all models was important and did not degrade model performance, and the best performing models were parsimonious, typically having only 1-3 predictors. Third, stratification by geographic domain (PFT, geographic region) improved model performance in comparison to global models without stratification. Fourth, for the vast majority of strata, the best performing models were fit using square root transformation of field AGBD and/or height metrics. There was considerable variability in model performance across geographic strata, and areas with sparse training data and/or high AGBD values had the poorest performance. These models are used to produce global predictions of AGBD, but will be improved in the future as more and better training data become available

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome