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Performance of methods for SARS-CoV-2 variant detection and abundance estimation within mixed population samples

The accurate identification of SARS-CoV-2 (SC2) variants and estimation of their abundance in mixed population samples (e.g., air or wastewater) is imperative for successful surveillance of community level trends. Assessing the performance of SC2 variant composition estimators (VCEs) should improve our confidence in public health decision making. Here, we introduce a linear regression based VCE and compare its performance to four other VCEs: two re-purposed DNA sequence read classifiers (Kallisto and Kraken2), a maximum-likelihood based method (Lineage deComposition for Sars-Cov-2 pooled samples (LCS)), and a regression based method (Freyja). We simulated DNA sequence datasets of known variant composition from both Illumina and Oxford Nanopore Technologies (ONT) platforms and assessed the performance of each VCE. We also evaluated VCEs performance using publicly available empirical wastewater samples collected for SC2 surveillance efforts. Bioinformatic analyses were performed with a custom NextFlow workflow (C-WAP, CFSAN Wastewater Analysis Pipeline). Relative root mean squared error (RRMSE) was used as a measure of performance with respect to the known abundance and concordance correlation coefficient (CCC) was used to measure agreement between pairs of estimators. Based on our results from simulated data, Kallisto was the most accurate estimator as it had the lowest RRMSE, followed by Freyja. Kallisto and Freyja had the most similar predictions, reflected by the highest CCC metrics. We also found that accuracy was platform and amplicon panel dependent. For example, the accuracy of Freyja was significantly higher with Illumina data compared to ONT data; performance of Kallisto was best with ARTICv4. However, when analyzing empirical data there was poor agreement among methods and variations in the number of variants detected (e.g., Freyja ARTICv4 had a mean of 2.2 variants while Kallisto ARTICv4 had a mean of 10.1 variants). This work provides an understanding of the differences in performance of a number of VCEs and how accurate they are in capturing the relative abundance of SC2 variants within a mixed sample (e.g., wastewater). Such information should help officials gauge the confidence they can have in such data for informing public health decisions.

60 APPLIED LIFE SCIENCES↗

Impact of including second and later cancers in cause-specific survival estimates using population-based registry data

Background. Second or later primary cancers account for approximately 20% of incident cases in the United States. Currently, cause-specific survival (CSS) analyses exclude these cancers because the cause of death (COD) classification algorithm was available only for first cancers. The authors added rules for later cancers to the Surveillance, Epidemiology, and End Results cause-specific death classification algorithm and evaluated CSS to include individuals with prior tumors. Methods. The authors constructed 2 cohorts: 1) the first ever primary cohort, including patients whose first cancer was diagnosed during 2000 through 2016) and 2) the earliest matching primary cohort, including patients with any cancer who matched the selection criteria irrespective of whether it was the first or a later cancer diagnosed during 2000 through 2016. The cohorts' CSS estimates were compared using follow-up through December 31, 2017. The new rules were used in the second cohort for patients whose first cancers during 2000 through 2016 were their second or later cancers. Results. Overall, there were no statistically significant differences in CSS estimates between the 2 cohorts. Estimates were similar by age, stage, race, and time since diagnosis, except for patients with leukemia and those aged 65 to 74 years (3.4 percentage point absolute difference). Conclusions. The absolute difference in CSS estimates for the first cancer ever cohort versus earliest of any cancers cohort in the study period was small for most cancer types. As the number of newly diagnosed patients with prior cancers increases, the algorithm will make CSS more inclusive and enable estimating survival for a group of patients with cancer for whom life tables are not available or life tables are available but do not capture other-cause mortality appropriately.

Survival Analysis↗

Estimation of Untracked Geosynchronous Population from Short-Arc Angles-Only Observations

Telescope observations of the geosynchronous regime will observe two basic types of objects --- objects related to geosynchronous earth orbit (GEO) satellites, and objects in highly elliptical geosynchronous transfer orbits (GTO). Because telescopes only measure angular rates, the GTO can occasionally mimic the motion of GEO objects over short arcs. A GEO census based solely on short arc telescope observations may be affected by these ``interlopers''. A census that includes multiple angular rates can get an accurate statistical estimate of the GTO population, and that then can be used to correct the estimate of the geosynchronous earth orbit population.

Healy, Liam↗

Bayesian Estimation of Earth’s Undiscovered Mineralogical Diversity Using Noninformative Priors

Recently, statistical distributions have been explored to provide estimates of the mineralogical diversity of Earth, and Earth-like planets. In this paper, a Bayesian approach is introduced to estimate Earth’s undiscovered mineralogical diversity. Samples are generated from a posterior distribution of the model parameters using Markov chain Monte Carlo simulations such that estimates and inference are directly obtained. It was previously shown that the mineral species frequency distribution conforms to a generalized inverse Gauss–Poisson (GIGP) large number of rare events model. Even though the model fit was good, the population size estimate obtained by using this model was found to be unreasonably low by mineralogists. In this paper, several zero-truncated, mixed Poisson distributions are fitted and compared, where the Poisson-lognormal distribution is found to provide the best fit. Subsequently, the population size estimates obtained by Bayesian methods are compared to the empirical Bayes estimates. Species accumulation curves are constructed and employed to estimate the population size as a function of sampling size. Finally, the relative abundances, and hence the occurrence probabilities of species in a random sample, are calculated numerically for all mineral species in Earth’s crust using the Poisson-lognormal distribution. These calculations are connected and compared to the calculations obtained in a previous paper using the GIGP model for which mineralogical criteria of an Earth-like planet were given.

Bayesian statistics↗

Statistical Estimation of Orbital Debris Populations with a Spectrum of Object Size

Orbital debris is a real concern for the safe operations of satellites. In general, the hazard of debris impact is a function of the size and spatial distributions of the debris populations. To describe and characterize the debris environment as reliably as possible, the current NASA Orbital Debris Engineering Model (ORDEM2000) is being upgraded to a new version based on new and better quality data. The data-driven ORDEM model covers a wide range of object sizes from 10 microns to greater than 1 meter. This paper reviews the statistical process for the estimation of the debris populations in the new ORDEM upgrade, and discusses the representation of large-size (greater than or equal to 1 m and greater than or equal to 10 cm) populations by SSN catalog objects and the validation of the statistical approach. Also, it presents results for the populations with sizes of greater than or equal to 3.3 cm, greater than or equal to 1 cm, greater than or equal to 100 micrometers, and greater than or equal to 10 micrometers. The orbital debris populations used in the new version of ORDEM are inferred from data based upon appropriate reference (or benchmark) populations instead of the binning of the multi-dimensional orbital-element space. This paper describes all of the major steps used in the population-inference procedure for each size-range. Detailed discussions on data analysis, parameter definition, the correlation between parameters and data, and uncertainty assessment are included.

Xu, Y. -l↗

Spacesuit Sizing by Multivariate Simulation: Case Study for Liquid Cooling and Ventilation Garment

A technique was developed to assess the fit of spacesuit garment liquid cooling and ventilation garment (LCVG). A fit scoring scheme was built from the spacesuit sizing requirements and guidelines, and the accommodated proportion of the wearer population was estimated from statistically synthesized pseudo population data. The method evaluated different scenarios of LCVG sizing systems including 1) baseline 7-size system, 2) 7-sizes with target body dimensions iteratively adjusted for maximum fit, and 3) 9-sizes with iterative adjustments. Overall, the baseline sizing system showed 81% accommodation rate, while the hypothetical new systems in-tegrating iterative adjustments for 7- and 9-sizes predictively indicated that accommodation could improve up to 92 and 97%. The proposed method provided a structured metric to quantify fit performance of a garment sizing system, which can be further applied to different spacesuit component, PPE and garment designs.

Han Kim↗

Growth phase estimation for abundant bacterial populations sampled longitudinally from human stool metagenomes

Longitudinal sampling of the stool has yielded important insights into the ecological dynamics of the human gut microbiome. However, human stool samples are available approximately once per day, while commensal population doubling times are likely on the order of minutes-to-hours. Despite this mismatch in timescales, much of the prior work on human gut microbiome time series modeling has assumed that day-to-day fluctuations in taxon abundances are related to population growth or death rates, which is likely not the case. Here, we propose an alternative model of the human gut as a stationary system, where population dynamics occur internally and the bacterial population sizes measured in a bolus of stool represent a steady-state endpoint of these dynamics. We formalize this idea as stochastic logistic growth. We show how this model provides a path toward estimating the growth phases of gut bacterial populations in situ. We validate our model predictions using an in vitro Escherichia coli growth experiment. Finally, we show how this method can be applied to densely-sampled human stool metagenomic time series data. We discuss how these growth phase estimates may be used to better inform metabolic modeling in flow-through ecosystems, like animal guts or industrial bioreactors.

59 BASIC BIOLOGICAL SCIENCES↗

LandCast Mosaic: Reconstructing Global Population Distributions, 1975-2025

LandCast Mosaic (LCM) provides a global, high-resolution gridded population dataset spanning 1975–2025, representing annual, scenario-consistent estimates of daytime, nighttime, and ambient population distributions. LCM builds on the 2025 LandScan Mosaic (LSM) population data by backcasting to earlier years using historical changes in built-surface area derived from the Global Human Settlement Layer (GHSL) and authoritative population counts from international datasets. The workflow scales 2025 building-informed gridded population estimates according to observed changes in built surface, applies linear interpolation for intermediate years, and normalizes estimates to match administrative- and country-level totals. The resulting dataset offers consistent, globally gridded population estimates over fifty years, suitable for temporal analyses of population dynamics, disaster risk modeling, and urban planning applications.

97 MATHEMATICS AND COMPUTING↗

Space Radiation Cancer, Circulatory Disease and CNS Risks for Near Earth Asteroid and Mars Missions: Uncertainty Estimates for Never-Smokers

The uncertainties in estimating the health risks from galactic cosmic rays (GCR) and solar particle events (SPE) are a major limitation to the length of space missions and the evaluation of potential risk mitigation approaches. NASA limits astronaut exposures to a 3% risk of exposure induced cancer death (REID), and protects against uncertainties in risks projections using an assessment of 95% confidence intervals after propagating the error from all model factors (environment and organ exposure, risk coefficients, dose-rate modifiers, and quality factors). Because there are potentially significant late mortality risks from diseases of the circulatory system and central nervous system (CNS) which are less well defined than cancer risks, the cancer REID limit is not necessarily conservative. In this report, we discuss estimates of lifetime risks from space radiation and new estimates of model uncertainties are described. The key updates to the NASA risk projection model are: 1) Revised values for low LET risk coefficients for tissue specific cancer incidence, with incidence rates transported to an average U.S. population to estimate the probability of Risk of Exposure Induced Cancer (REIC) and REID. 2) An analysis of smoking attributable cancer risks for never-smokers that shows significantly reduced lung cancer risk as well as overall cancer risks from radiation compared to risk estimated for the average U.S. population. 3) Derivation of track structure based quality functions depends on particle fluence, charge number, Z and kinetic energy, E. 4) The assignment of a smaller maximum in quality function for leukemia than for solid cancers. 5) The use of the ICRP tissue weights is shown to over-estimate cancer risks from SPEs by a factor of 2 or more. Summing cancer risks for each tissue is recommended as a more accurate approach to estimate SPE cancer risks. 6) Additional considerations on circulatory and CNS disease risks. Our analysis shows that an individual s history of smoking exposure has a larger impact on GCR risk estimates than amounts of radiation shielding or age at exposure (amongst adults). Risks for never-smokers compared to the average U.S. population are estimated to be reduced between 30% and 60% dependent on model assumptions. Lung cancer is the major contributor to the reduction for never-smokers, with additional contributions from circulatory diseases and cancers of the stomach, liver, bladder, oral cavity and esophagus, and leukemia. The relative contribution of CNS risks to the overall space radiation detriment is potentially increased for never-smokers such as most astronauts. Problems in estimating risks for former smokers and the influence of second-hand smoke are discussed. Compared to the LET approximation, the new track structure derived radiation quality functions lead to a reduced risk for relativistic energy particles and increased risks for intermediate energy particles. Revised estimates for the number of safe days in space at solar minimum for heavy shielding conditions are described for never-smokers and the average U.S. population. Results show that missions to near Earth asteroids (NEA) or Mars violate NASA's radiation safety standards with the current levels of uncertainties. Greater improvements in risk estimates for never-smokers are possible, and would be dependent on improved understanding of risk transfer models, and elucidating the role of space radiation on the various stages of disease formation (e.g. initiation, promotion, and progression).

Cucinotta, Francis A.↗

Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice

The output potential of proliferating populations in either the developing or the adult nervous system is critically dependent on the length of the cell cycle (T(c)) and the size of the proliferating population. We developed a new approach for analyzing the cell cycle, the 'Saturate and Survive Method' (SSM), that also reveals the dynamic behaviors in the proliferative population and estimates of the size of the proliferating population. We used this method to analyze the proliferating population of the adult dentate gyrus in 60 day old mice of two inbred strains, C57BL/6J and BALB/cByJ. The results show that the number of cells labeled by exposure to BUdR changes dramatically with time as a function of the number of proliferating cells in the population, the length of the S-phase, cell division, the length of the cell cycle, dilution of the S-phase label, and cell death. The major difference between C57BL/6J and BALB/cByJ mice is the size of the proliferating population, which differs by a factor of two; the lengths of the cell cycle and the S-phase and the probability that a newly produced cell will die within the first 10 days do not differ in these two strains. This indicates that genetic regulation of the size of the proliferating population is independent of the genetic regulation of cell death among those newly produced cells. The dynamic changes in the number of labeled cells as revealed by the SSM protocol also indicate that neither single nor repeated daily injections of BUdR accurately measure 'proliferation.'.

Non-NASA Center↗

Feature selection and causal analysis for microbiome studies in the presence of confounding using standardization

Abstract Background Microbiome studies have uncovered associations between microbes and human, animal, and plant health outcomes. This has led to an interest in developing microbial interventions for treatment of disease and optimization of crop yields which requires identification of microbiome features that impact the outcome in the population of interest. That task is challenging because of the high dimensionality of microbiome data and the confounding that results from the complex and dynamic interactions among host, environment, and microbiome. In the presence of such confounding, variable selection and estimation procedures may have unsatisfactory performance in identifying microbial features with an effect on the outcome. Results In this manuscript, we aim to estimate population-level effects of individual microbiome features while controlling for confounding by a categorical variable. Due to the high dimensionality and confounding-induced correlation between features, we propose feature screening, selection, and estimation conditional on each stratum of the confounder followed by a standardization approach to estimation of population-level effects of individual features. Comprehensive simulation studies demonstrate the advantages of our approach in recovering relevant features. Utilizing a potential-outcomes framework, we outline assumptions required to ascribe causal, rather than associational, interpretations to the identified microbiome effects. We conducted an agricultural study of the rhizosphere microbiome of sorghum in which nitrogen fertilizer application is a confounding variable. In this study, the proposed approach identified microbial taxa that are consistent with biological understanding of potential plant-microbe interactions. Conclusions Standardization enables more accurate identification of individual microbiome features with an effect on the outcome of interest compared to other variable selection and estimation procedures when there is confounding by a categorical variable.

59 BASIC BIOLOGICAL SCIENCES↗

Abundance and Migration Success of Overshoot Steelhead in the Upper Columbia River

Abstract Summer steelhead Oncorhynchus mykiss may enter freshwater almost a year before spawning and potentially make long migrations (>1,000 km) to interior headwater habitats. However, in response to suboptimal freshwater habitat conditions (e.g., warmer water temperatures), adult summer steelhead may exhibit complex behaviors during upstream migration in the Columbia River basin. Steelhead may migrate upstream of their natal tributary (hereafter, referred to as “overshoot”) and spend days to several months before subsequently migrating downstream (hereafter, referred to as “fallback”) to their natal tributary to spawn. An expansion of an existing Bayesian patch occupancy model, derived from observations of adult steelhead that were PIT-tagged to estimate population-specific abundance upstream of the tagging location, incorporated downstream detection locations to estimate the abundance of overshoot fallbacks. Overshoot steelhead abundance at the tagging location was estimated based on the relationship between the number of known overshoot fallbacks (i.e., the number of steelhead that overshot and successfully migrated downstream to their natal tributary) and their model-estimated abundance. During the study period (2010–2017), the annual mean proportion of overshoot steelhead that successfully migrated downstream of the tagging location (Priest Rapids Dam) was 0.59 (SD = 0.14). The number of dams encountered by overshoot steelhead during their downstream migration was negatively correlated with their downstream migration success probability. Improved downstream passage survival for adult steelhead will increase the abundance of affected populations while reducing potential genetic introgression of upstream populations (i.e., strays). This is the first study to estimate the abundance of overshoot and fallback steelhead, providing the data necessary for scientists to estimate potential conservation benefits of improved downstream survival. For example, surface flow passage routes (e.g., sluiceways and temporary spillway weirs) are very effective in guiding and passing adult steelhead downstream of Columbia River hydroelectric projects and data from this assessment show that changes in dam operations throughout the downstream migration period may maximize conservation benefits.

Murdoch, Andrew R. (ORCID:0000000324827689)↗

The Small Size Debris Population at GEO from Optical Observations

We have observed the geosynchronous orbit (GEO) debris population at sizes smaller than 10 cm using optical observations with the 6.5-m Magellan telescope 'Walter Baade' at the Las Campanas Observatory in Chile. The IMACS f/2 imaging camera with a 0.5-degree diameter field of view has been used in small area surveys of the GEO regime to study the population of optically faint GEO debris. The goal is to estimate the population of GEO debris that is fainter than can be studied with 1-meter class telescopes. A significant population of objects fainter than R = 19th magnitude has been found. These objects have observed with angular rates consistent with circular orbits and orbital inclinations up to 15 degrees at GEO. A sizeable number of these objects have significant brightness variations ("flashes") during the 5-second exposure, which suggest rapid changes in the albedo-projected size product.

Seitzer, Patrick↗

Strong Lensing Cosmology with Population-level Calibrated Neural Ratio Estimation

Strong gravitational lensing contains key information about cosmic acceleration. Modern and next-generation galaxy imaging surveys are expected to provide high-quality data on $\mathcal{O}(10^5)$ galaxy-galaxy lensing systems. The plethora and complexity of the data are likely to present computational challenges for parameter inference methods for fitting high-dimensional likelihoods, which are often analytically intractable. Neural Ratio Estimation (NRE) efficiently computes individual likelihood ratios that can be combined into population-level posteriors. We use simulations to study the capacity of NRE to jointly predict the dark energy equation-of-state parameter $w$ and the total matter density $Ω_{m}$ from lensing images and companion spectroscopic information. We also introduce a post hoc posterior coverage calibration procedure that mitigates the model overconfidence that is typically found in neural density estimation applications. Our experiments show that the errors on both parameters decrease with increasing inference population sizes. In particular, for 100 lenses in a standard $Λ$CDM Universe, our calibrated NRE model achieves median fractional uncertainty of $22.8\%$ in $w$ and $2.9\%$ in $Ω_{m}$. This proof of concept demonstrates a potentially scalable approach for efficient cosmological parameter inference with large populations of galaxy-scale lenses observed in future surveys.

Jarugula, Sreevani [Fermilab] (ORCID:0000000253867↗

Demographics of Investigators Involved in OSSA-Funded Research

The birth of the U.S. civil space program and the subsequent, dramatic growth in the ranks of the space science research population occurred in the 1950s and 1960s'. The large, post- Sputnik/ Apollo buildup in space program manpower is now approximately one career-lifetime in the past. It is therefore natural to anticipate that a large fraction of the space program engineers, scientists, and managers who pioneered the early exploration of space are approaching retirement. Such a "retirement wave" bodes both a loss of manpower and, more fundamentally, a loss of experience from the civil-space manpower base. Such losses could play a critical role constraining in NASA's ability to expand or maintain its technical capabilities. If this indeed applies to the NASA space science research population, then the potential for problems is exacerbated by the anticipated growth in flight rates, data volume, and data-set diversity which will accompany the planned expansion in the OSSA science effort during the 1990s and 2000s. The purpose of this study was to describe the OSSA PI/Co-I population and to determine the degree to which the OSSA space science investigator population faces a retirement wave, and to estimate the future population of PIs in the 1990-2010 era. To conduct such a study, we investigated the present demographics of the PI and Co-1 population contained in the NASA/OSSA Announcement of Opportunity (AO) mailing list. PIs represent the "leadership" class of the OSSA scientific researcher population, and Co-Is represent one important, oncoming component of the "replacement" generation. Using the PI population data, we then make projection estimates of the future PI population from 1991 through 2010, under various NASA growth/PI demand scenarios.

Stern, S. Alan↗