Results for “reliability analysis” — Page 24

DOE OSTI2026

Hydrogeological assessment of CO2 containment assurance and wellbore integrity at a Gulf Coast storage site

Abstract A large-scale carbon capture and storage (CCS) initiative on the Texas Gulf Coast serves as a premier demonstration of the U.S. Department of Energy’s CarbonSAFE program. Targeting deep saline formations, specifically Oligo-Miocene deltaic sequences, the project aims to establish technical and commercial viability for geologic CO2 storage within a major industrial corridor. This study provides a rigorous hydrogeological assessment to support Class VI permitting by quantifying the high degree of containment security. Utilizing a compositional reservoir simulator, we developed a suite of 27 distinct simulation cases to evaluate vertical plume dynamics near both planned injection wells and proximal legacy infrastructure. To ensure numerical accuracy near wellbores, we implemented a refined mesh strategy, determining that a 5.6 ft × 5.6 ft grid refinement offered the optimal balance between computational efficiency and descriptive precision. The modeling framework utilized a systematic sensitivity-based approach to evaluate the mechanical redundancy of the subsurface system by performing a bounding analysis of wellbore interfaces against hypothetical high-permeability microannuli. By systematically isolating competing physical drivers, including permeability, porosity, gas hysteresis, thermal gradients, salinity, and solubility trapping (quantified via Henry’s law with dynamically adjusted coefficients), this work moves beyond binary assessments to establish a nuanced hierarchy of containment factors. The results confirm that primary trapping mechanisms (e.g., gas hysteresis and solubility), combined with the site's unique geomechanical stratigraphy, significantly restrict vertical mobility and reinforce the robust containment security of the reservoir. Baseline results demonstrate substantial vertical separation between the CO2 plume and the upper confining system, ensuring robust containment. Sensitivity analysis reveals that even under highly conservative bounding scenarios—assuming theoretical 10-Darcy pathways at specific wellbore locations—the 2,900-ft thick multi-layered confining zone remains a reliable barrier. In these hypothetical upper-bound cases, peak upward fluxes of CO2 and saltwater after 15 years of injection remain localized and dissipate rapidly within the lower sections of the confining interval, leaving the integrity of the seal uncompromised. Furthermore, the study identifies that while localized wellbore pathways define theoretical upper bounds of vertical migration, the Area of Review (AoR) is primarily sensitive to regional thermal gradients and hysteresis, which can influence the AoR by over 3,000 acres in pessimistic configurations. Also, primary trapping mechanisms, specifically gas hysteresis and solubility, work in tandem with the Gulf Coast’s unique geomechanical stratigraphy to significantly restrict vertical mobility. Ductile, smectite-rich mudstones facilitate natural borehole convergence and the self-healing of potential conduits, creating a natural geomechanical bridge that effectively mitigates migration potential at both current injection points and legacy-well locations. This comprehensive modeling effort demonstrates that the integration of high-resolution wellbore simulations and regional geomechanical observations confirms the long-term storage security of the studied site, providing a physics-based foundation for industrial-scale CCS deployments. This modeling framework establishes a baseline for future research into coupled geomechanical effects, such as time-dependent borehole convergence, to further refine long-term containment projections. Acknowledgements We thank the Gulf Coast Carbon Center (GCCC) at the Bureau of Economic Geology for foundational research support. We appreciate Alex Bump for technical guidance and David Hoffman for model mesh generation. This work used TACC’s Frontera cluster for simulations and CMG Ltd. software licenses provided to UT-Austin. This material is based upon work supported by the Department of Energy under Award Number DE-FE0032338. Disclaimer This material is based upon work supported by the U.S. Department of Energy’s Fossil Energy and Carbon Management Office under the CarbonSAFE program, award Number DE-FE0032338. The views expressed herein do not necessarily represent the views of the U.S. Department of Energy or the United States Government.

58 GEOSCIENCES↗

DOE OSTI2026

Hydrogeological assessment of CO2 containment assurance and wellbore integrity at a Gulf Coast storage site

Abstract A large-scale carbon capture and storage (CCS) initiative on the Texas Gulf Coast serves as a premier demonstration of the U.S. Department of Energy’s CarbonSAFE program. Targeting deep saline formations, specifically Oligo-Miocene deltaic sequences, the project aims to establish technical and commercial viability for geologic CO2 storage within a major industrial corridor. This study provides a rigorous hydrogeological assessment to support Class VI permitting by quantifying the high degree of containment security. Utilizing a compositional reservoir simulator, we developed a suite of 27 distinct simulation cases to evaluate vertical plume dynamics near both planned injection wells and proximal legacy infrastructure. To ensure numerical accuracy near wellbores, we implemented a refined mesh strategy, determining that a 5.6 ft × 5.6 ft grid refinement offered the optimal balance between computational efficiency and descriptive precision. The modeling framework utilized a systematic sensitivity-based approach to evaluate the mechanical redundancy of the subsurface system by performing a bounding analysis of wellbore interfaces against hypothetical high-permeability microannuli. By systematically isolating competing physical drivers, including permeability, porosity, gas hysteresis, thermal gradients, salinity, and solubility trapping (quantified via Henry’s law with dynamically adjusted coefficients), this work moves beyond binary assessments to establish a nuanced hierarchy of containment factors. The results confirm that primary trapping mechanisms (e.g., gas hysteresis and solubility), combined with the site's unique geomechanical stratigraphy, significantly restrict vertical mobility and reinforce the robust containment security of the reservoir. Baseline results demonstrate substantial vertical separation between the CO2 plume and the upper confining system, ensuring robust containment. Sensitivity analysis reveals that even under highly conservative bounding scenarios—assuming theoretical 10-Darcy pathways at specific wellbore locations—the 2,900-ft thick multi-layered confining zone remains a reliable barrier. In these hypothetical upper-bound cases, peak upward fluxes of CO2 and saltwater after 15 years of injection remain localized and dissipate rapidly within the lower sections of the confining interval, leaving the integrity of the seal uncompromised. Furthermore, the study identifies that while localized wellbore pathways define theoretical upper bounds of vertical migration, the Area of Review (AoR) is primarily sensitive to regional thermal gradients and hysteresis, which can influence the AoR by over 3,000 acres in pessimistic configurations. Also, primary trapping mechanisms, specifically gas hysteresis and solubility, work in tandem with the Gulf Coast’s unique geomechanical stratigraphy to significantly restrict vertical mobility. Ductile, smectite-rich mudstones facilitate natural borehole convergence and the self-healing of potential conduits, creating a natural geomechanical bridge that effectively mitigates migration potential at both current injection points and legacy-well locations. This comprehensive modeling effort demonstrates that the integration of high-resolution wellbore simulations and regional geomechanical observations confirms the long-term storage security of the studied site, providing a physics-based foundation for industrial-scale CCS deployments. This modeling framework establishes a baseline for future research into coupled geomechanical effects, such as time-dependent borehole convergence, to further refine long-term containment projections. Acknowledgements We thank the Gulf Coast Carbon Center (GCCC) at the Bureau of Economic Geology for foundational research support. We appreciate Alex Bump for technical guidance and David Hoffman for model mesh generation. This work used TACC’s Frontera cluster for simulations and CMG Ltd. software licenses provided to UT-Austin. This material is based upon work supported by the Department of Energy under Award Number DE-FE0032338. Disclaimer This material is based upon work supported by the U.S. Department of Energy’s Fossil Energy and Carbon Management Office under the CarbonSAFE program, award Number DE-FE0032338. The views expressed herein do not necessarily represent the views of the U.S. Department of Energy or the United States Government.

58 GEOSCIENCES↗

DOE OSTI2024

Dynamic Modeling and Analysis for Large-Scale Renewable Energy Integration

Lina He will present dynamic modeling techniques for the integration of large-scale renewable energy systems. The presentation will address the challenges associated with high renewable penetration and provide frameworks for ensuring smooth and reliable grid operations.

Dynamic modeling, large-scale renewable integratio↗

DOE OSTI2025

Analysis of SPND Material Candidates for Real-Time Neutron Spectrum Monitoring Poster

The future of the nuclear industry will be shaped by advanced reactor designs requiring innovative instrumentation for safe operation. A key area of innovation is the ability to accurately and reliably monitor the neutron energy spectrum during operations, which would also enhance the experimental capabilities of existing research reactors. To address this need, our research focuses on the potential use of Self-Powered Neutron Detectors (SPNDs) for real-time neutron spectrum monitoring. We investigated various candidate materials for SPNDs by evaluating their energy-dependent reaction rates. Promising materials were further modeled using MCNP to determine the free electron production per neutron across the neutron energy spectrum, approximating their energy-dependent signal sensitivity. Our findings identified Samarium (Sm) and Gadolinium (Gd) as top candidates for thermal neutrons, Hafnium (Hf) and Thulium (Tm) for epithermal neutrons, and Tantalum (Ta) for fast neutrons. These materials will undergo future experimental validation to confirm the modeled responses and assess their feasibility for real-time neutron spectrum measurements.

46 - INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AN↗

DOE OSTI2024

Comparative Analyses of Bioequivalence Assessment Methods for In Vitro Permeation Test Data

ABSTRACT For topical, dermatological drug products, an in vitro option to determine bioequivalence (BE) between test and reference products is recommended. In particular, in vitro permeation test (IVPT) data analysis uses a reference‐scaled approach for two primary endpoints, cumulative penetration amount (AMT) and maximum flux ( J max ), which takes the within donor variability into consideration. In 2022, the Food and Drug Administration (FDA) published a draft IVPT guidance that includes statistical analysis methods for both balanced and unbalanced cases of IVPT study data. This work presents a comprehensive evaluation of various methodologies used to estimate critical parameters essential in assessing BE. Specifically, we investigate the performance of the FDA draft IVPT guidance approach alongside alternative empirical and model‐based methods utilizing mixed‐effects models. Our analyses include both simulated scenarios and real‐world studies. In simulated scenarios, empirical formulas consistently demonstrate robustness in approximating the true model, particularly in effectively addressing treatment–donor interactions. Conversely, the effectiveness of model‐based approaches heavily relies on precise model selection, which significantly influences their results. The research emphasizes the importance of accurate model selection in model‐based BE assessment methodologies. It sheds light on the advantages of empirical formulas, highlighting their reliability compared to model‐based approaches and offers valuable implications for BE assessments. Our findings underscore the significance of robust methodologies and provide essential insights to advance their understanding and application in the assessment of BE, employed in IVPT data analysis.

Leon, Sami↗

DOE OSTI2025

Quantification of Oxygen Vacancies in SrFe0.5Cr0.5O3−δ Thin Films: Correlating Lattice Expansion with Oxidation State Variability

Oxygen vacancies (VO), even in the dilute regime, can significantly impact the physical and chemical properties of complex oxides. It is however challenging to reliably detect and adequately quantify such defects in thin film samples where the VO concentration and distribution may further vary in response to interfacial strain. Here, we present a method to quantify VO concentrations in SrFe0.5Cr0.5O3−δ (SFCO) epitaxial thin films. Through coherent Bragg rod analysis, X-ray absorption spectroscopy, and theoretical modeling, we systematically correlate the c-axis lattice expansion detected in SFCO films with a VO concentration gradient. Our results reveal a nearly linear relationship between oxygen off-stoichiometry and out-of-plane lattice expansion in coherently strained SFCO films, with δ increasing from 0.32 to 0.52 and the lattice expanding by ∼1.0%. Moreover, a significant decrease in Cr oxidation state (from Cr5+ to Cr3+) is observed as the VO concentration increases, while the Fe oxidation state remains fixed at Fe3+. Our findings provide a reliable way to quantify oxygen stoichiometry in complex oxides, offering a pathway to design materials with precisely tailored structure–property relationships.

Hossain, Mohammad Delower↗

DOE OSTI2026

Data Centers Gap Analysis [Slides]

Data centers and other large loads are a significant driver of unprecedented, near-term demand growth in the United States. Power system planners, utilities, regulators, and other stakeholders are grappling with how to integrate data centers on the system without comprising reliability, resiliency, and energy affordability. NLR is pursuing work to develop a siting and decision-making tool that would draw on power systems modeling expertise to achieve granular representation of trade-offs involved in data center sitting and development. This slide deck supports the same workstream by reviewing the literature to identify mitigation options to facilitate near-term integration of large loads and by presenting options for pursuing data development and/or modeling projects to improve representation of siting options.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

DOE OSTI2024

An empirical analysis of supply offers in the ERCOT operating reserves markets

Here, this paper seeks to improve theoretical and empirical understanding of supplier dynamics in wholesale markets for operating reserves, which have been understudied compared to energy markets. We begin by identifying several economic factors that unit owners may consider when submitting offers into operating reserves auctions in two-stage, co-optimized markets common across much of North America. Next, we analyze historical offer data from the Electric Reliability Council of Texas (ERCOT) market to assess whether actual reserve market behavior aligns with expectations based on economic theory, as well as with commonly used assumptions in electricity market modeling efforts. We find that the aggregate supply of operating reserves in ERCOT varies meaningfully over time, becoming more expensive during summer afternoons, which is consistent with theoretical expectations but contradicts the typical modeling assumption of temporally invariant reserve offers. Analysis of offers made by individual units uncovers additional insights, such as the existence of large offer pattern differences by unit owner and the tendency of battery storage units to submit very low offer prices. We conclude by discussing how our findings can be integrated into electricity market modeling assumptions to improve alignment with observed operating reserve offer inputs and pricing outcomes.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

DOE OSTI2026

Bridging Control and Deployment: A Cross-Layer Analysis of Scalable Building Cluster Control

Building cluster control has emerged as a promising approach for enabling flexible and coordinated operation of distributed building systems, yet its transition from pilot demonstrations to routine grid-interactive operation remains limited. This paper argues that this gap cannot be explained by control algorithms alone. Instead, it arises from interacting barriers in communication infrastructure, data and semantic interoperability, uncertainty management, stakeholder participation, market design, and policy support. Accordingly, the paper reviews both technical and non-technical barriers to building cluster control. Technical challenges include heterogeneous devices and protocols, communication latency and reliability, distributed decision-making, and uncertainty propagation across aggregated loads. Non-technical barriers include user participation, stakeholder coordination, incentive allocation, and data governance. Existing solution approaches are synthesized, including semantic interoperability frameworks, edge and hierarchical communication architectures, distributed and transactive control strategies, uncertainty-aware optimization, policy mechanisms, and market reforms. Based on this analysis, two research directions are identified: testing infrastructures that can evaluate control performance under realistic multi-building conditions, and abstraction methods that allow building clusters to interact with other energy sectors through standardized flexibility representations. Overall, the paper provides a structured review of how building cluster control can move from isolated demonstrations toward reproducible, market-compatible, and grid-relevant implementation.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

DOE OSTI2024

Climate change is intensifying rainfall erosivity and soil erosion in West Africa

Soil erosion is a critical environmental challenge with significant implications for agriculture, water quality, and ecosystem stability. Understanding its dynamics is essential for sustainable environmental management and societal welfare. Here, we analyze rainfall erosivity and erosion patterns across West Africa (WAF) during the historical (1982–2014), near future (2028–2060), and far future (2068–2100) periods under Shared Socioeconomic Pathways (SSPs 370 and 585). Using bias-corrected-downscaled (BCD) climate models validated against reference data, we ensure an accurate representation of rainfall—a key driver of erosivity (R-factor) and soil erosion. We compare Renard's approach and the Modified Fournier Index (MFI) to calculate the R-factor and note a strong correlation. However, Renard's method shows slightly lower accuracy in Sierra Leone, Guinea, and The Gambia, likely due to its inability to capture high-intensity, short-duration rainfall events. In contrast, the MFI, utilizing continuous rain gauge data, proves more reliable for these regions. We also attribute fluctuations in erosivity, such as those seen during the 2003 West Africa floods, to synoptic weather patterns influenced by multiple climate processes. Furthermore, our analysis reveals regions where future soil erosion could exceed 20 t/ha/yr due to climate change. Under the SSP 370 scenario, soil erosion in WAF is projected to rise by 14.84 % in the near future and 18.65 % in the far future, increasing further under SSP 585 to 19.86 % and 23.49 %, respectively. The most severe increases are expected in Benin and Nigeria, with Nigeria potentially facing a 66.41 % rise in erosion by the far future under SSP 585. These findings highlight the region's exposure to intensified climatic conditions and underscore the urgent need for targeted soil management and climate adaptation strategies to mitigate erosion's ecological and socioeconomic impacts.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2025

Parameterized anomalous transport model for current-carrying collisionless plasmas in pulsed power inertial confinement fusion

Current delivery in pulsed power inertial confinement fusion is influenced by collisionless current-carrying microturbulent plasmas, which are sourced from electrode surfaces. In this setting, the lower hybrid drift instability—triggered by plasma acceleration—is a leading candidate driver of difficult-to-predict momentum and energy transport. To characterize the nonlinear state of the microturbulent plasma, a parameterized anomalous transport model is developed for the instability, with analytic formulas for anomalous collision frequency, resistivity, and species heating rates. The formulas are expressed in terms of linear-theory variables and four dimensionless parameters that characterize the macroscopic plasma state. The model is built on linear theory analysis, power law analysis, and quasilinear theory analysis, and is validated using a series of nonlinear continuum kinetic Vlasov–Poisson simulations. The theoretical and computational investigation demonstrates that the anomalous collision frequency associated with the instability can be reliably approximated, within about a factor of five or better, by the unscaled linear theory growth rate of the fastest-growing wavenumber mode. This finding enables efficient calculation of anomalous resistivity and species heating rates over a wide range of plasma conditions, resulting in improved predictive capabilities.

Complex functions↗

DOE OSTI2026

A Survey on the Expanding Scope and Interdisciplinary Opportunities for Processing-in-Memory Techniques

Processing-in-Memory (PIM) is emerging as a practical path to overcome the limitations of traditional von Neumann architectures. At its core, PIM systems implement computing primitives such as logic operations and multiply-accumulate acceleration through compute-in-memory, near-memory processing, or hybrid designs. The role of memory cells varies widely across technologies, acting as inputs, outputs, or analog accumulators through bit-lines and sense amplifiers. This diversity creates trade-offs in precision, bandwidth, latency, and programmability, making it difficult to build a unified understanding on the progress of the field. In this survey, we organize recent advances of PIM into three areas. First, we discuss the progress on the architectural optimizations of PIM and its integration with both DRAM and emerging non-volatile memories. Second, we examine how PIM is being used to accelerate key computing domains, including generative AI workloads and high-performance kernels, along with new approaches. Third, we highlight the growing adoption of PIM in computational sciences, where it is being applied to solve interdisciplinary problems such as genome analysis, mRNA quantification, mass spectrometry, quantum circuit simulation, wave modeling, and secure computation. Finally, we synthesize the major challenges that continue to slow PIM adoption, including manufacturing constraints, power delivery, thermal reliability, data consistency, runtime and memory-management coordination, and the difficulty of building portable software abstractions without sacrificing commercial viability. This work provides an updated, structured perspective on PIM’s potential across computing and computational sciences and the barriers that must be solved for it to reach its full impact.

Asifuzzaman, Kazi [Oak Ridge National Laboratory (↗

DOE OSTI2024

Numerical Investigation of Butterfly Valve Performance in Variable Valve Sizes, Positions and Flow Regimes

Reliability and efficiency of valves are necessary for precise control and sufficient heat-flow to heat application plants for the integrated energy systems of nuclear power plants (NPPs). Strategic Management Analysis Requirement and Technology (SMART) valves’ ability to control flow and assess environmental parameters stands out for these requirements. Their ability to sustain the downstream flow rate, prevent reverse flow, and maintain pressure in the heat transport loop is much more efficient with the integration of sensors and intelligent algorithms. For assessing valve performance and monitoring, mechanical design and operating conditions are two important parameters. In this study, the butterfly valves of three different sizes are simulated with water and steam using STAR-CCM+ in various flow regimes and positions to analyze performance parameters to strategize an automated control system for efficiently balancing the heat–transport network. Also, flow behavior is studied using velocity and pressure fields for valve–body geometry optimization. It can be observed, through performance parameters, that the valves are suitable for operation between 30° and 90° positions with significantly low loss coefficients and high flow coefficients, and the performance parameters follow a certain pattern in both water and steam flow in each scenario.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

DOE OSTI2024

The Sustainable Decarbonization Challenge

Many countries have decarbonization plans that include transitioning to clean energy. Because of this, PV deployment is projected to at least double or triple in the next ten years. As we ramp up manufacturing and deployment, we aim to sustainably establish secure and just supply chains while reducing environmental impacts. This talk presents our analysis of the virgin material demands, addresses waste concerns regarding quantity and toxicity, and establishes sustainability actions that the PV community can take to ensure sustainability. The takeaway actions are prioritizing reliable, high-quality, and long-lived PV modules and enabling the fast deployment needed for decarbonization via more research and effective communication.

circular economy↗

DOE OSTI2025

Establishing In-House Titration Capabilities: Part I. Hydroxyl Group Titration through Acetic Anhydride Acetylation

This lessons learned document provides a detailed analysis of the hydroxy termination titration methods employed for determining hydroxyl group content in various chemical samples. The primary focus is on the evaluation of techniques such as ASTM E222 and their practical applications in laboratory settings. Through examination of method selection, sample preparation, and titration execution, key insights have been identified that enhance the accuracy and reliability of results. Notable findings include the advantages of using pressure bottle methods for improved heating uniformity and reduced solvent loss, as well as the challenges associated with endpoint detection in dark-colored solutions. Recommendations for alternative sampling and titration techniques are proposed to address these challenges. This document serves as a valuable resource for enhancing the effectiveness and efficiency of hydroxy termination titration methods in chemical analysis.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2026

Analysis of Power Electronic Solutions for Wide-Range Wave Energy Input

Wave energy is a largely untapped energy source with the potential to provide 290 TWh per year to the continental United States. As a new technology, wave energy converters are less efficient and reliable compared to established energy sources, leaving the vast energy of the sea largely unutilized. Wave energy is uniquely inconsistent, with large fluctuations. Paired with harsh operating environments and difficulty in repair, the power electronics designed to harvest wave energy need to be reliable, cost-effective, and able to work in a wide operating band. The literature on existing power electronics in wave energy converters and lessons learned across other industries provide a framework of topologies to simulate. WEC-Sim, an open-source hydrodynamic platform in MATLAB Simulink developed by the National Laboratory of the Rockies, was used to simulate a wide range of power electronics under a variety of wave conditions. This paper provides a comprehensive investigation into existing wave energy power electronics converters, state-of-the-art topologies that can be applied to wave energy, and novel solutions to wave conversion.

16 TIDAL AND WAVE POWER↗

DOE OSTI2025

From Machine Learning to Machine Reasoning: A Model-based Approach to Analyze Equipment Reliability Data

In current nuclear power plants (NPPs) a large amount of condition-based data which can be used to assess and monitor component health and performance. Assessing component health from such data can be performed with a large variety of methods. While the analysis of numeric data can be performed with several methods, the extraction of information from textual data remains a challenge. Currently employed natural language processing (NLP) methods do not really provide quantitative information that might be contained in IRs. In addition, the integration of numeric and textual data to identify possible causal relationships between data elements is still an unresolved challenge. This paper presents an approach to extract information from textual (e.g., incident or maintenance reports) and numeric data that relies on model based system engineer (MBSE) models. MBSE are diagrams designed to represent system and component dependencies (from both a form and functional point of view). In our approach, MBSE models emulate system engineer knowledge about component/system architecture. NLP methods are employed to perform syntactic and semantic analyses. Syntactic analysis analyzes the grammatical structure of a sentence while semantic analysis is designed to analyze the logic structure of a sentence. An innovative element of our approach is that semantic analysis uses MBSE models to identify links between textual elements. Similarly, numeric data is directly linked to elements of the MBSE models in order to map which functions are being monitored.

97 - MATHEMATICS AND COMPUTING↗

DOE OSTI2025

Evaluating the limitations of Bayesian metabolic control analysis

AbstractBayesian Metabolic Control Analysis (BMCA) has emerged as a promising framework for inferring metabolic control coefficients in data-limited scenarios by integrating Bayesian inference with linlog rate laws. However, its predictive accuracy and limitations remain underexplored. This study systematically evaluates BMCA’s ability to infer elasticity values, flux control coefficients (FCCs), and concentration control coefficients (CCCs) under varying data availability conditions using three synthetic metabolic network models. Our findings highlight the strengths and weaknesses of BMCA, guiding its application in metabolic engineering and emphasizing the need for methodological refinements.Author summaryUnderstanding how enzymes control metabolic pathways is crucial for optimizing biomanufacturing and synthetic biology applications. Bayesian Metabolic Control Analysis (BMCA) is a promising computational method that integrates Bayesian inference with metabolic control analysis to estimate key control parameters, even in cases with limited experimental data. However, the accuracy and limitations of BMCA remain unclear. In this study, we systematically evaluate BMCA using three synthetic metabolic networks to determine how different types of physiological data impact its predictive performance. We find that BMCA requires flux and enzyme concentration data for accurate predictions, while external metabolite concentrations contribute little. Additionally, BMCA fails to predict elasticity values beyond a magnitude of 1.5 and reliably infer allosteric regulation, even when strong regulatory interactions exist. In addition, BMCA does not accurately rank metabolic control points, which may limit its utility in identifying key enzymes in engineered pathways. Our work provides practical insights into when and how BMCA can be applied, guiding future research in metabolic modeling and control analysis.

Shin, Janis (ORCID:0000000216572455)↗