Uncertainty-Aware Adaptation of Large Language Models for Protein-Protein Interaction Analysis
Explore the source record for details and available documents.
Engineering topics
Publications and source records attributed to Urban, Nathan M..
Explore the source record for details and available documents.
Abstract. Antarctica's Lambert Glacier drains about one-sixth of the ice from the East Antarctic Ice Sheet and is considered stable due to the strong buttressing provided by the Amery Ice Shelf. While previous projections of the sea-level contribution from this sector of the ice sheet have predicted significant mass loss only with near-complete removal of the ice shelf, the ocean warming necessary for this was deemed unlikely. Recent climate projections through 2300 indicate that sufficient ocean warming is a distinct possibility after 2100. This work explores the impact of parametric uncertainty on projections of the response of the Lambert–Amery system (hereafter “the Amery sector”) to abrupt ocean warming through Bayesian calibration of a perturbed-parameter ice-sheet model ensemble. We address the computational cost of uncertainty quantification for ice-sheet model projections via statistical emulation, which employs surrogate models for fast and inexpensive parameter space exploration while retaining critical features of the high-fidelity simulations. To this end, we build Gaussian process (GP) emulators from simulations of the Amery sector at a medium resolution (4–20 km mesh) using the Model for Prediction Across Scales (MPAS)-Albany Land Ice (MALI) model. We consider six input parameters that control basal friction, ice stiffness, calving, and ice-shelf basal melting. From these, we generate 200 perturbed input parameter initializations using space filling Sobol sampling. For our end-to-end probabilistic modeling workflow, we first train emulators on the simulation ensemble and then calibrate the input parameters using observations of the mass balance, grounding line movement, and calving front movement with priors assigned via expert knowledge. Next, we use MALI to project a subset of simulations to 2300 using ocean and atmosphere forcings from a climate model for both low- and high-greenhouse-gas-emission scenarios. From these simulation outputs, we build multivariate emulators by combining GP regression with principal component dimension reduction to emulate multivariate sea-level contribution time series data from the MALI simulations. We then use these emulators to propagate uncertainty from model input parameters to predictions of glacier mass loss through 2300, demonstrating that the calibrated posterior distributions have both greater mass loss and reduced variance compared to the uncalibrated prior distributions. Parametric uncertainty is large enough through about 2130 that the two projections under different emission scenarios are indistinguishable from one another. However, after rapid ocean warming in the first half of the 22nd century, the projections become statistically distinct within decades. Overall, this study demonstrates an efficient Bayesian calibration and uncertainty propagation workflow for ice-sheet model projections and identifies the potential for large sea-level rise contributions from the Amery sector of the Antarctic Ice Sheet after 2100 under high-greenhouse-gas-emission scenarios.
Not Available
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Abstract Pharmacodynamic (PD) models are mathematical models of cellular reaction networks that include drug mechanisms of action. These models are useful for studying predictive therapeutic outcomes of novel drug therapies in silico. However, PD models are known to possess significant uncertainty with respect to constituent parameter data, leading to uncertainty in the model predictions. Furthermore, experimental data to calibrate these models is often limited or unavailable for novel pathways. In this study, we present a Bayesian optimal experimental design approach for improving PD model prediction accuracy. We then apply our method using simulated experimental data to account for uncertainty in hypothetical laboratory measurements. This leads to a probabilistic prediction of drug performance and a quantitative measure of which prospective laboratory experiment will optimally reduce prediction uncertainty in the PD model. The methods proposed here provide a way forward for uncertainty quantification and guided experimental design for models of novel biological pathways.
Modern climate projections lack adequate spatial and temporal resolution due to computational constraints. A consequence is inaccurate and imprecise predictions of critical processes such as storms. Hybrid methods that combine physics with machine learning (ML) have introduced a new generation of higher fidelity climate simulators that can sidestep Moore’s Law by outsourcing compute-hungry, short, high-resolution simulations to ML emulators. However, this hybrid ML-physics simulation approach requires domain-specific treatment and has been inaccessible to MLexperts because of lack of training data and relevant, easy-to-use workflows. Wepresent ClimSim, the largest-ever dataset designed for hybrid ML-physics research. It comprises multi-scale climate simulations, developed by a consortium of climate scientists and ML researchers. It consists of 5.7 billion pairs of multivariate input and output vectors that isolate the influence of locally-nested, high-resolution, high-fidelity physics on a host climate simulator’s macro-scale physical state. The dataset is global in coverage, spans multiple years at high sampling frequency, and is designed such that resulting emulators are compatible with downstream coupling into operational climate simulators. We implement a range of deterministic and stochastic regression baselines to highlight the ML challenges and their scoring. The data (https://huggingface.co/datasets/LEAP/ClimSim_high-res2) and code(https://leap-stc.github.io/ClimSim)arereleasedopenlytosupport the development of hybrid ML-physics and high-fidelity climate simulations for the benefit of science and society.
Abstract. Multi-meter sea level rise (SLR) is thought to be possible within the next few centuries, with most of the uncertainty originating from the Antarctic land ice contribution. One source of uncertainty relates to the ice sheet model initialization. Since ice sheets have a long response time (compared to other Earth system components such as the atmosphere), ice sheet model initialization methods can have significant impacts on how the ice sheet responds to future forcings. To assess this, we generated 25 different ice sheet spin-ups, using the Community Ice Sheet Model (CISM) at a 4 km resolution. During each spin-up, we varied two key parameters known to impact the sensitivity of the ice sheet to future forcing: one related to the sensitivity of the ice shelf melt rate to ocean thermal forcing (TF) and the other related to the basal friction. The spin-ups all nudge toward observed thickness and enforce a no-advance calving criterion, such that all final spin-up states resemble observations but differ in their melt and friction parameter settings. Each spin-up was then forced with future ocean thermal forcings from 13 different CMIP6 models under the Shared Socioeconomic Pathway (SSP)5-8.5 emissions scenario and modern climatological surface mass balance data. Our results show that the effects of the ice sheet and ocean parameter settings used during the spin-up are capable of impacting multi-century future SLR predictions by as much as 2 m. By the end of this century, the effects of these choices are more modest, but still significant, with differences of up to 0.2 m of SLR. We have identified a combined ocean and ice parameter space that leads to widespread mass loss within 500 years (low friction and high melt rate sensitivity). To explore temperature thresholds, we also ran a synthetically forced CISM ensemble that is focused on the Amundsen region only. Given certain ocean and ice parameter choices, Amundsen mass loss can be triggered with thermal forcing anomalies between 1.5 and 2 ∘C relative to the spin-up. Our results emphasize the critical importance of considering ice sheet and ocean parameter choices during spin-up for SLR predictions and suggest the importance of including glacial isostatic adjustment in ice sheet simulations.
Abstract. Antarctic ice shelves are vulnerable to warming ocean temperatures, and some have already begun thinning in response to increased basal melt rates. Sea level is therefore expected to rise due to Antarctic contributions, but uncertainties in its amount and timing remain largely unquantified. In particular, there is substantial uncertainty in future basal melt rates arising from multi-model differences in thermal forcing and how melt rates depend on that thermal forcing. To facilitate uncertainty quantification in sea level rise projections, we build, validate, and demonstrate projections from a computationally efficient statistical emulator of a high-resolution (4 km) Antarctic ice sheet model, the Community Ice Sheet Model version 2.1. The emulator is trained to a large (500-member) ensemble of 200-year-long 4 km resolution transient ice sheet simulations, whereby regional basal melt rates are perturbed by idealized (yet physically informed) trajectories. The main advantage of our emulation approach is that by sampling a wide range of possible basal melt trajectories, the emulator can be used to (1) produce probabilistic sea level rise projections over much larger Monte Carlo ensembles than are possible by direct numerical simulation alone, thereby providing better statistical characterization of uncertainties, and (2) predict the simulated ice sheet response under differing assumptions about basal melt characteristics as new oceanographic studies are published, without having to run additional numerical ice sheet simulations. As a proof of concept, we propagate uncertainties about future basal melt rate trajectories, derived from regional ocean models, to generate probabilistic sea level rise estimates for 100 and 200 years into the future.
This paper focuses on the problem of quantifying the effects of model-structure uncertainty in the context of time-evolving dynamical systems. This is motivated by multi-model uncertainty in computer physics simulations: developers often make different modeling choices in numerical approximations and process simplifications, leading to different numerical codes that ostensibly represent the same underlying dynamics. We consider model-structure inference as a two-step methodology: the first step is to perform system identification on numerical codes for which it is possible to observe the full state; the second step is structural uncertainty quantification, in which the goal is to search candidate models "close" to the numerical code surrogates for those that best match a quantity of interest (QOI) from some empirical data sets. Here, we (1) define a discrete, local representation of the structure of a partial differential equation, which we refer to as the "local dynamical operator" (LDO); (2) identify model structure nonintrusively from numerical code output; (3) nonintrusively construct a reduced-order model (ROM) of the numerical model through POD-DEIM-Galerkin projection; (4) perturb the ROM dynamics to approximate the behavior of alternate model structures; and (5) apply Bayesian inference and energy conservation laws to calibrate a LDO to a given QOI. We demonstrate these techniques using the two-dimensional rotating shallow water equations as an example system.
Here, we implement a variance-based distance metric (D n ) to objectively assess skill of sea ice models when multiple output variables or uncertainties in both model predictions and observations need to be considered. The metric compares observations and model data pairs on common spatial and temporal grids improving upon highly aggregated metrics (e.g., total sea ice extent or volume) by capturing the spatial character of model skill. The D n metric is a gamma-distributed statistic that is more general than the χ 2 statistic commonly used to assess model fit, which requires the assumption that the model is unbiased and can only incorporate observational error in the analysis. The D n statistic does not assume that the model is unbiased, and allows the incorporation of multiple observational data sets for the same variable and simultaneously for different variables, along with different types of variances that can characterize uncertainties in both observations and the model. This approach represents a step to establish a systematic framework for probabilistic validation of sea ice models. The methodology is also useful for model tuning by using the D n metric as a cost function and incorporating model parametric uncertainty as part of a scheme to optimize model functionality. We apply this approach to evaluate different configurations of the standalone Los Alamos sea ice model (CICE) encompassing the parametric uncertainty in the model, and to find new sets of model configurations that produce better agreement than previous configurations between model and observational estimates of sea ice concentration and thickness.