Search NASA⌕ Search

SEARCH · Search NASA

Results for “prognostic”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

A Binomial Stochastic Framework for Efficiently Modeling Discrete Statistics of Convective Populations

Abstract Understanding the coupling between convective clouds and the general circulation, as well as addressing the gray zone problem in convective parameterization, requires insight into the genesis and maintenance of spatial patterns in cumulus cloud populations. In this study, a simple toy model for recreating populations of interacting convective objects as distributed over a two‐dimensional Eulerian grid is formulated to this purpose. Key elements at the foundation of the model include i) a fully discrete formulation for capturing discrete behavior in convective properties at small population sample sizes, ii) object age‐dependence for representing life‐cycle effects, and iii) a prognostic number budget allowing for object interactions and co‐existence of multiple species. A primary goal is to optimize the computational efficiency of this system. To this purpose the object birth rate is represented stochastically through a spatially aware Bernoulli process. The same binomial stochastic operator is applied to horizontal advection of objects, conserving discreteness in object number. The applicability to atmospheric convection as well as behavior implied by the formulation is assessed. Various simple applications of the BiOMi model (Binomial Objects on Microgrids) are explored, suggesting that important convective behavior can be captured at low computational cost. This includes i) subsampling effects and associated powerlaw scaling in the convective gray zone, ii) stochastic predator‐prey behavior, iii) the downscale turbulent energy cascade, and iv) simple forms of spatial organization and convective memory. Consequences and opportunities for convective parameterization in next‐generation weather and climate models are discussed.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Large Methane Emissions From the Pantanal During Rising Water‐Levels Revealed by Regularly Measured Lower Troposphere CH 4 Profiles

Abstract The Pantanal region of Brazil is the largest seasonally flooded tropical grassland and, according to local chamber measurements, a substantial CH 4 source. CH 4 emissions from wetlands have recently become of heightened interest because global atmospheric 13 CH 4 data indicate they may contribute to the resumption of atmospheric CH 4 growth since 2007. We have regularly measured vertical atmospheric profiles for 2 years in the center of the Pantanal with the objectives to obtain an estimate of CH 4 emissions using an atmospheric approach, and provide information about flux seasonality and its relation to controlling factors. Boundary layer‐free troposphere differences observed in the Pantanal are large compared to other wetlands. Total emissions based on a planetary boundary layer budgeting technique are 2.0–2.8 TgCH 4 yr −1 (maximum flux ∼0.4 gCH 4 m −2 d −1 ) while those based on a Bayesian inversion using an atmospheric transport model are ∼3.3 TgCH 4 yr −1 . Compared to recent estimates for Amazonia (∼41 ± 3 TgCH 4 yr −1 , maximum flux ∼0.3 gCH 4 m −2 d −1 ) these emissions are not that large. Our Pantanal data suggest a clear flux seasonality with CH 4 being released in large amounts just after water levels begin to rise again after minimum levels have been reached. CH 4 emissions decline substantially once the maximum water level has been reached. While predictions with prognostic wetland CH 4 emission models agree well with the magnitude of the fluxes, they disagree with the phasing. Our approach shows promise for detecting and understanding longer‐term trends in CH 4 emissions and the potential for future wetlands CH 4 emissions climate feedbacks.

Gloor, M.↗
DOE OSTI2021

Disentangling the Effects of Vapor Pressure Deficit and Soil Water Availability on Canopy Conductance in a Seasonal Tropical Forest During the 2015 El Niño Drought

In land models used in Earth system models, vegetation water stress is heuristically related to soil water matric potential, and root water uptake in soil layers is simply proportional to root density to meet the transpiration demand. The efficiency of roots utilizing deeper soil water under water stress cannot be well represented, but it is of critical importance for transpiration regulation and carbon flux. To improve modeling of tropical forest response to drought, a plant hydrodynamic scheme (HYDRO), adapted from a trait-based model in the Functionally Assembled Terrestrial Ecosystem Simulator (FATES), has been implemented in the Energy Exascale Earth System Model (E3SM) Land Model (ELM) to represent the hydraulic dynamics and root water uptake strategy. The adapted model conforms to the big-leaf photosynthesis model in ELM. Vegetation water stress in the model is a function of prognostic leaf water potential and is used to regulate stomatal conductance. Point simulations were performed at two tropical forest sites in the Amazon and Panama. Model sensitivity to the numerical solver, plant hydraulic traits, soil properties, and atmospheric forcing has been evaluated. Our results showed that, even though water stress factors calculated at our study sites using HYDRO are comparable to that simulated by the heuristic water stress model, soil moisture prediction is improved with soil water redistributions through roots. Simulated results using HYDRO is not as sensitive to plant hydraulic traits measured for different tree species as to the soil properties and atmospheric forcing. Simplified numerical solver may cause inaccuracy as to where roots uptake water. This study suggests that plant hydrodynamic representation is critical for improved simulations of soil moisture under water stresses.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Simulations With the Marine Biogeochemistry Library (MARBL)

Abstract The Marine Biogeochemistry Library (MARBL) is a prognostic ocean biogeochemistry model that simulates marine ecosystem dynamics and the coupled cycles of carbon, nitrogen, phosphorus, iron, silicon, and oxygen. MARBL is a component of the Community Earth System Model (CESM); it supports flexible ecosystem configuration of multiple phytoplankton and zooplankton functional types; it is also portable, designed to interface with multiple ocean circulation models. Here, we present scientific documentation of MARBL, describe its configuration in CESM2 experiments included in the Coupled Model Intercomparison Project version 6 (CMIP6), and evaluate its performance against a number of observational data sets. The model simulates present‐day air‐sea CO 2 flux and many aspects of the carbon cycle in good agreement with observations. However, the simulated integrated uptake of anthropogenic CO 2 is weak, which we link to poor thermocline ventilation, a feature evident in simulated chlorofluorocarbon distributions. This also contributes to larger‐than‐observed oxygen minimum zones. Moreover, radiocarbon distributions show that the simulated circulation in the deep North Pacific is extremely sluggish, yielding extensive oxygen depletion and nutrient trapping at depth. Surface macronutrient biases are generally positive at low latitudes and negative at high latitudes. CESM2 simulates globally integrated net primary production (NPP) of 48 Pg C yr −1 and particulate export flux at 100 m of 7.1 Pg C yr −1 . The impacts of climate change include an increase in globally integrated NPP, but substantial declines in the North Atlantic. Particulate export is projected to decline globally, attributable to decreasing export efficiency associated with changes in phytoplankton community composition.

Meteorology & Atmospheric Sciences↗
DOE OSTI2022

Incorporating Microtopography in a Land Surface Model and Quantifying the Effect on the Carbon Cycle

Abstract Northern peatlands are a terrestrial carbon store, with an annual sink of 0.1 Pg C yr −1 and a total storage estimate of 547 Pg C. Northern peatlands are also major contributors of atmospheric methane. Most land surface models do not accurately represent peatland carbon emissions, partly because they do not represent the hydrologic cycle and/or microtopography adequately. Interactions between water table depth and microtopography in peatlands influence decomposition and modulate CO 2 and CH 4 fluxes. A modified version of the land surface component of the Energy Exascale Earth System Model, was recently created to represent the microtopography and hydrology of a raised dome bog in northern Minnesota, USA. In this study, three microtopographic parameters are analyzed in the modified version: hummock height, hummock‐hollow spacing, and percent hollow. Terrestrial laser scanning observations are used to set uncertainty bounds for these parameters. Our model experiment results suggest that carbon‐related quantities of interest (QOI) were typically the most sensitive to hummock height, and those QOI (especially net ecosystem exchange, NEE) were sensitive to interactions between parameters. Furthermore, NEE was most relatively influenced by microtopographic parameters in the model, varying by 35%. We found that increasing hummock height resulted in more C being stored in plant tissue and less in soil organic matter. This coincided with decreases in Sphagnum and increases in Picea and shrub net primary production. These results suggest that future studies may consider extending prognostic capabilities of carbon cycling by incorporating hummock hollow microtopography into earth system models.

58 GEOSCIENCES↗
DOE OSTI2023

Evaluating Northern Hemisphere Growing Season Net Carbon Flux in Climate Models Using Aircraft Observations

Understanding terrestrial ecosystems and their response to anthropogenic climate change requires quantification of land-atmosphere carbon exchange. However, top-down and bottom-up estimates of large-scale land-atmosphere fluxes, including the northern extratropical growing season net flux (GSNF), show significant discrepancies. We developed a data-driven metric for the GSNF using atmospheric carbon dioxide concentration observations collected during the High-Performance Instrumented Airborne Platform for Environmental Research Pole-to-Pole Observations and Atmospheric Tomography Mission flight campaigns. This aircraft-derived metric is bias-corrected using three independent atmospheric inversion systems. We estimate the northern extratropical GSNF to be 5.7 ± 0.3 Pg C and use it to evaluate net biosphere productivity from the Coupled Model Intercomparison Project phase 5 and 6 (CMIP5 and CMIP6) models. While the model-to-model spread in the GSNF has decreased in the CMIP6 models relative to that of the CMIP5 models, there is still disagreement on the magnitude and timing of seasonal carbon uptake with most models underestimating the GSNF and overestimating the length of the growing season relative to the observations. We also use an emergent constraint approach to estimate annual northern extratropical gross primary productivity to be 56 ± 17 Pg C, heterotrophic respiration to be 25 ± 13 Pg C, and net primary productivity to be 28 ± 12 Pg C. The flux inferred from these aircraft observations provides an additional constraint on large-scale gross fluxes in prognostic Earth system models that may ultimately improve our ability to accurately predict carbon-climate feedbacks.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Westward-Propagating Moisture Mode Over the Tropical Western Hemisphere

A westward-propagating Rossby-like wave signal is found to explain a large fraction of the intraseasonal variance in cloud brightness over the Western Hemisphere. A series of diagnostic criteria suggest that this wave is a moisture mode: its moisture anomalies dominate the distribution of moist static energy (MSE) and are in phase with the precipitation anomalies; and the thermodynamic equation obeys the weak temperature gradient approximation. Further, the wave propagates westward due to zonal moisture advection by the mean flow and is maintained by radiative heating and meridional moisture advection. These properties compare favorably with the westward propagating Rossby mode in an equatorial beta-plane model with prognostic moisture, mean meridional moisture gradient, and mean zonal wind. These results underscore the importance of water vapor in the dynamics of slowly evolving tropical systems, and the limitations of dry shallow water theory that rely on a “reduced equivalent depth” to represent moist dynamics.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

An Efficient Bayesian Approach to Learning Droplet Collision Kernels: Proof of Concept Using “Cloudy,” a New n -Moment Bulk Microphysics Scheme

The small-scale microphysical processes governing the formation of precipitation particles cannot be resolved explicitly by cloud resolving and climate models. Instead, they are represented by microphysics schemes that are based on a combination of theoretical knowledge, statistical assumptions, and fitting to data (“tuning”). Historically, tuning was done in an ad hoc fashion, leading to parameter choices that are not explainable or repeatable. Recent work has treated it as an inverse problem that can be solved by Bayesian inference. The posterior distribution of the parameters given the data—the solution of Bayesian inference—is found through computationally expensive sampling methods, which require over $\mathcal{O}$(10 5 ) evaluations of the forward model; this is prohibitive for many models. We present a proof of concept of Bayesian learning applied to a new bulk microphysics scheme named “Cloudy,” using the recently developed Calibrate-Emulate-Sample (CES) algorithm. Cloudy models collision-coalescence and collisional breakup of cloud droplets with an adjustable number of prognostic moments and with easily modifiable assumptions for the cloud droplet mass distribution and the collision kernel. The CES algorithm uses machine learning tools to accelerate Bayesian inference by reducing the number of forward evaluations needed to $\mathcal{O}$(10 2 ). It also exhibits a smoothing effect when forward evaluations are polluted by noise. In a suite of perfect-model experiments, we show that CES enables computationally efficient Bayesian inference of parameters in Cloudy from noisy observations of moments of the droplet mass distribution. In an additional imperfect-model experiment, a collision kernel parameter is successfully learned from output generated by a Lagrangian particle-based microphysics model.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Uncertain Spatial Pattern of Future Land Use and Land Cover Change and Its Impacts on Terrestrial Carbon Cycle Over the Arctic–Boreal Region of North America

Land use and land cover change (LULCC) represents a key process of human-Earth system interaction and has profound impacts on terrestrial ecosystem carbon cycling. As a key input for ecosystem models, future gridded LULCC data is typically spatially downscaled from regional LULCC projections by integrated assessment models, such as the Global Change Analysis Model (GCAM). The uncertainty associated with the different spatial downscaling methods and its impacts on the subsequent model projections have been historically ignored and rarely examined. This study investigated this problem using two representative spatial downscaling methods and focused on their impacts on the carbon cycle over the Arctic-Boreal Vulnerability Experiment (ABoVE) domain, where extensive LULCC is expected. Specifically, we used the Future Land Use Simulation model (FLUS) and the Demeter model to generate 0.25° gridded LULCC data (i.e., LULCC FLUS and LULCC Demeter , respectively) with the same input of regional LULCC projections from GCAM, under both the low (i.e., SSP126) and high (i.e., SSP585) greenhouse gas emission scenarios. The two sets of downscaled LULCC were used to drive the Community Land Model version 5 and prognostically simulate the terrestrial carbon cycle dynamics over the 21st century. The results suggest large spatial-temporal differences between LULCC FLUS and LULCC Demeter , and the spatial distributions of the needleleaf evergreen boreal tree, broadleaf deciduous boreal tree, broadleaf deciduous boreal shrub, and C3 arctic grass are particularly different under both SSP126 and SSP585. Additionally, the spatiotemporal differences are larger under SSP126 than SSP585, due to more intensive LULCC under SSP126 than SSP585 from GCAM projection. The differences in LULCC further lead to large discrepancies in the spatial patterns of projected gross primary productivity, ecosystem respiration, and net ecosystem exchange, which represent more than 79% of the contributions of future LULCC in 2100. Additionally, the difference in carbon flux under SSP126 is generally larger than those under SSP585. This study highlights the importance of considering the uncertainties induced by the spatial downscaling process in future LULCC projections and carbon cycle simulations.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

A 1D Model for Nucleation of Ice From Aerosol Particles: An Application to a Mixed‐Phase Arctic Stratus Cloud Layer

Abstract Mixed‐phase clouds (MPCs) have been identified as significant contributors to uncertainties in climate projections, attributable to model representation of processes controlling the formation and loss of supercooled water droplets and ice particles from the atmosphere. Arctic MPCs are commonly widespread and long‐lived, with sustained ice crystal formation processes that challenge current understanding. This study examines the ice‐nucleating particle (INP) reservoir dynamics governing immersion‐mode heterogeneous freezing in an observed case of Arctic MPCs using a simplified 1D aerosol‐cloud model. The model setup includes prescribed dynamical forcings and thermodynamic profiles, and represents INPs as multicomponent and polydisperse particle size distributions. Diagnostic and prognostic approaches to immersion freezing parameterization are compared, including time‐independent (singular) number‐ and surface area‐based descriptions and a time‐dependent description following classical nucleation theory (CNT). The choice of freezing parameterization defines the size of the INP reservoir. The CNT‐based description yields an orders of magnitude larger INP reservoir than the singular parameterizations, which is the dominant factor for sustained ice crystal formation. The efficiency of the freezing process and cloud cooling are of secondary importance. A diagnostic treatment neglecting INP loss is only accurate when the INP reservoir size is large and INP depletion weak. Since a larger INP reservoir sustains ice crystal formation substantially longer, and ice water path scales with ice crystal concentrations for the conditions considered, resolving the source of differences in INP reservoir dynamics due to model implementation is a high priority for advancing climate model physics.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

A Non‐Intrusive Machine Learning Framework for Debiasing Long‐Time Coarse Resolution Climate Simulations and Quantifying Rare Events Statistics

Abstract Due to the rapidly changing climate, the frequency and severity of extreme weather is expected to increase over the coming decades. As fully‐resolved climate simulations remain computationally intractable, policy makers must rely on coarse‐models to quantify risk for extremes. However, coarse models suffer from inherent bias due to the ignored “sub‐grid” scales. We propose a framework to non‐intrusively debias coarse‐resolution climate predictions using neural‐network (NN) correction operators. Previous efforts have attempted to train such operators using loss functions that match statistics. However, this approach falls short with events that have longer return period than that of the training data, since the reference statistics have not converged. Here, the scope is to formulate a learning method that allows for correction of dynamics and quantification of extreme events with longer return period than the training data. The key obstacle is the chaotic nature of the underlying dynamics. To overcome this challenge, we introduce a dynamical systems approach where the correction operator is trained using reference data and a coarse model simulation nudged toward that reference. The method is demonstrated on debiasing an under‐resolved quasi‐geostrophic model and the Energy Exascale Earth System Model (E3SM). For the former, our method enables the quantification of events that have return period two orders longer than the training data. For the latter, when trained on 8 years of ERA5 data, our approach is able to correct the coarse E3SM output to closely reflect the 36‐year ERA5 statistics for all prognostic variables and significantly reduce their spatial biases.

Barthel Sorensen, B.↗
DOE OSTI2025

Assessing Clouds in GFDL's AM4.0 With Different Microphysical Parameterizations Using the Satellite Simulator Package COSP

We evaluate cloud simulations using satellite simulators against multiple observational data sets. These simulators have been run within the Geophysical Fluid Dynamics Laboratory's Atmosphere Model version 4.0 (AM4.0), as well as an alternative configuration where a fully two‐moment Morrison‐Gettelman cloud microphysical parameterization with prognostic precipitation (MG2) is applied, denoted as AM4‐MG2. The modeled cloud spatial distributions, vertical profiles, phase partitioning, cloud‐to‐precipitation transitions, and radiative effects compare reasonably well with satellite observations. Model biases include the under‐prediction of total and low‐level clouds, especially optically thin/intermediate clouds with cloud optical depth of less than 23, but the over‐prediction of thick clouds, indicating “too few, too bright” biases. These biases counteract each other, and give rise to reasonable estimates of cloud radiative effects. The underestimate of low‐level clouds is associated with too early and too frequent drizzle/precipitation formation. The precipitation bias is improved in AM4‐MG2, where the autoconversion scheme initiates the precipitation more realistically. There also exist discrepancies between models and observations for midlevel and high‐level clouds. Additional biases include the underestimate of liquid cloud fraction and the overestimate of ice cloud fraction.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

Sensitivities of Large Eddy Simulations of Aerosol Plume Transport and Cloud Response

Abstract Cloud responses to surface‐based sources of aerosol perturbation partially depend on how turbulent transport of the aerosol to cloud base affects the spatial and temporal distribution of aerosol. Here, scenarios of plume injection below a marine stratocumulus cloud are modeled using large eddy simulations coupled to a prognostic bulk aerosol and cloud microphysics scheme. Both passive plumes, consisting of an inert tracer, and active plumes are investigated, where the latter are representative of saltwater droplet plumes such as have been proposed for marine cloud brightening. Passive plume scenarios show higher in‐plume cloud brightness (relative to out‐of‐plume) due to the predominant transport of the passive plume tracer from the near‐surface to the cloud layer within updrafts. These updrafts rise into brighter areas within the cloud deck, even in the absence of an aerosol perturbation associated with an active plume. Comparing albedo at in‐plume to out‐of‐plume locations associates the inert plume with the brightest cloud locations, without any causal effect of the plume on the cloud. Numerical sensitivities are first assessed to establish a suitable model configuration. Then sensitivity to particle injection rate is investigated. Trade‐offs are identified between the number of injected particles and the suppressive effect of droplet evaporation on plume loft and spread. Furthermore, as the near‐field in‐plume brightening effect does not depend significantly on injection rate given a suitable definition of perturbed versus unperturbed regions of the flow, plume area is a key controlling factor on the overall cloud brightening effect of an aerosol perturbation.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

Physics or Knob‐Tuning? Tropical Anvil Peak Is Captured by GCMs

Tropical anvil clouds peak near 200 hPa and significantly impact Earth's climate, yet its physical realism in coarse‐resolution General Circulation Models (GCMs) remains debated. We examine anvil cloud formation by performing simulations with a GCM with a hierarchy of cloud fraction schemes ranging from a complex prognostic Tiedtke scheme to a simple binary scheme. All schemes consistently reproduce the anvil peak. The robust anvil peak arises because extremely cold temperatures at the upper troposphere facilitate frequent saturation events, producing clouds that disproportionately influence mean cloud fraction. Sensitivity experiments with enhanced evaporation of cloud condensate unexpectedly show increased anvil coverage, highlighting how slight evaporative moistening reinforces local saturation in cold upper‐tropospheric conditions. These results demonstrate that the tropical anvil cloud peak emerges from fundamental thermodynamic constraints, rather than specific cloud fraction parameterization choices.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

A Decadal Hybrid GCM Simulation Using Deep‐Learning‐Based Cloud and Convection Parameterization Generalized to a Warm Climate

A critical challenge for machine‐learning (ML) parameterization in global climate models (GCMs) is to achieve stable, accurate simulations under climates not seen during training. Previous studies have demonstrated promising offline performance and year‐long online stability in aquaplanet simulations but have encountered difficulties in real geography and under climate warming. Here we report that a GCM with real geography configuration using neural‐network‐based cloud and convection parameterization, trained exclusively with present‐day climate data, successfully performs a stable, decade‐long simulation of a warm climate with +4 K sea surface temperature (SST). The neural network (NN) is based on Han et al. (2023, https://doi.org/10.1029/2022ms003508 ) with additional inputs. The simulation captures the global precipitation distribution, surface temperatures, vertical atmospheric structures, and extreme precipitation very well, closely matching simulations from both the superparameterized CAM (SPCAM) and the conventional CAM5 in the warm climate without accuracy degradation compared to those in the baseline climate. Moreover, it produces a climate response to +4 K SST in atmospheric thermodynamic states and circulations similar to those from SPCAM and CAM5. Prognostic ablation tests on NN input variables show that the NN without convective memory as input suffers from numerical instability, and the NN without considering radiative variables and land fraction as input, or with reduced training samples produce less accurate results. To our knowledge, this is the first time an ML parameterization successfully achieves online extrapolation to a warm climate without using additional warm‐climate data for training. It demonstrates the potential of ML‐driven parameterizations for credible long‐term climate projections.

Atmosphere model↗
DOE OSTI2026

The Energy Exascale Earth System Model Version 3: 2. Overview of the Coupled System

The Energy Exascale Earth System Model version 3 (E3SMv3) represents the latest advancement in Earth system modeling developed by the U.S. Department of Energy (DOE). Building upon previous versions, E3SMv3 introduces significant updates across its coupled components to enhance capability and improve fidelity. The atmosphere component incorporates advancements in chemistry, aerosol-cloud interactions, convection, and microphysics. The ocean features a new time-stepping scheme and a higher-resolution unstructured mesh with sub-ice-shelf cavities, while the sea ice model integrates advanced snow and ice physics for more realistic cryospheric simulations. The land model introduces prognostic vegetation dynamics and a new sub-grid topographic treatment of solar radiation. A new tri-grid configuration harmonizes the horizontal grids of the land and river components for improved process coupling. It is enabled by a new non-linear remapping between the atmosphere and land. E3SMv3 underwent extensive testing through a comprehensive simulation campaign, including pre-industrial control, idealized CO 2 experiments, and historical simulations spanning 1850–2024. The model demonstrates significant improvements in simulating the evolution of the historical surface temperature, particularly addressing the “pothole cooling” bias in earlier versions. Reduced aerosol-related forcing contributes to more realistic radiative forcing and better alignment with the observational record. Ocean heat content (OHC) and sea ice trends are also improved as a result.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

CRL4A DTL degrades DNA-PKcs to modulate NHEJ repair and induce genomic instability and subsequent malignant transformation

Genomic instability induced by DNA damage and improper DNA damage repair is one of the main causes of malignant transformation and tumorigenesis. DNA double strand breaks (DSBs) are the most detrimental form of DNA damage, and nonhomologous end-joining (NHEJ) mechanisms play dominant and priority roles in initiating DSB repair. A well-studied oncogene, the ubiquitin ligase Cullin 4A (CUL4A), is reported to be recruited to DSB sites in genomic DNA, but whether it regulates NHEJ mechanisms of DSB repair is unclear. Here, we discovered that the CUL4A-DTL ligase complex targeted the DNA-PKcs protein in the NHEJ repair pathway for nuclear degradation. Overexpression of either CUL4A or DTL reduced NHEJ repair efficiency and subsequently increased the accumulation of DSBs. Moreover, we demonstrated that overexpression of either CUL4A or DTL in normal cells led to genomic instability and malignant proliferation. Consistent with the in vitro findings, in human precancerous lesions, CUL4A expression gradually increased with increasing malignant tendency and was negatively correlated with DNA-PKcs and positively correlated with γ-H2AX expression. Collectively, this study provided strong evidence that the CUL4A-DTL axis increases genomic instability and enhances the subsequent malignant transformation of normal cells by inhibiting NHEJ repair. These results also suggested that CUL4A may be a prognostic marker of precancerous lesions and a potential therapeutic target in cancer.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

The genomic and epigenomic evolutionary history of papillary renal cell carcinomas

Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA methylation data. In 29 tumors, up to 10 samples from the center to the periphery of each tumor, and metastatic samples in 2 cases, enable phylogenetic analysis of spatial features of clonal expansion, which shows congruent patterns of genomic and epigenomic evolution. In contrast to previous studies of ccRCC, in pRCC, driver gene mutations and most arm-level somatic copy number alterations (SCNAs) are clonal. These findings suggest that a single biopsy would be sufficient to identify the important genetic drivers and that targeting large-scale SCNAs may improve pRCC treatment, which is currently poor. While type 1 pRCC displays near absence of structural variants (SVs), the more aggressive type 2 pRCC and the rarer subtypes have numerous SVs, which should be pursued for prognostic significance.

59 BASIC BIOLOGICAL SCIENCES↗