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Advancements in NEAMS Tool Capabilities for Multiphysics Simulation of Fast Reactor Core Bowing and Identification of Validation Test Data

Under the U.S. Department of Energy Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Program, an integrated multiphysics approach is being developed to model the core bowing phenomena important to liquid metal-cooled fast reactors. Core bowing is an important passive safety mechanism in liquid metal-cooled fast reactors and involves Multiphysics effects including radiation transport, fluid flow, heat transfer, and mechanical response to temperature and flux gradients. This report summarizes recent progress on developing a multiphysics, MOOSE-based workflow to predict core bowing and associated reactivity feedback. Last year, thermal fluids and mechanics were coupled on a multi-assembly benchmark problem based on ABR-1000 design. This year, the reactor physics code Griffin was assessed for readiness of core bowing calculations. Preliminary integration of Griffin’s ring-heterogeneous model with thermal fluids and thermal mechanics solvers was performed. Specifically, thermal-mechanics and reactor physics were coupled for single- and multi-assembly problems, and reactor physics and subchannel methods were coupled for a single assembly model. Finally, the workflow of all three physics was preliminarily demonstrated on a single assembly model. Caveats and future development needed have been identified. To supplement the multiphysics demonstration, verification and assessment efforts of thermos-mechanical capabilities for modeling thermo-mechanical core bowing behavior were continued by analyzing IAEA Verification Problem 5 which includes radiation swelling and creep. Additionally, a small core reactor physics benchmark defined by Japan Atomic Energy Agency (JAEA) was performed to assess neutronics models for estimating reactivity feedback. Finally, Fast Flux Test Facility (FFTF) validation test data for core bowing phenomena has been identified and summarized, with a recommended path forward for validation once this capability is mature.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

High Power FPC Progress for EIC ESR Cavities

Electron-Ion Collider (EIC) is a next generation particle accelerator to be built at Brookhaven National Laboratory, in partnership with Thomas Jefferson National Accelerator Facility. In Electron Storage Ring (ESR), 18 single-cell 591 MHz SRF cavities are required to compensate for up to 10 MW energy loss due to synchronic radiation. Two high power FPCs for each cavity are used to deliver up to 800 kW power to the beam. The high power FPC were designed and reviewed. The FPC prototypes will be ready for high power test around mid-2026. This paper presents the latest development of FPC prototyping and path forward for FPC conditioning.

43 PARTICLE ACCELERATORS↗

Streamlined Approach for Environmental Restoration (SAFER) Plan for Corrective Action Unit 114: Area 25 EMAD Facility Nevada National Security Site, Nevada

This Streamlined Approach for Environmental Restoration (SAFER) Plan addresses the actions needed to achieve closure for Corrective Action Unit (CAU) 114, Area 25 EMAD Facility, identified in the Federal Facility Agreement and Consent Order (FFACO). CAU 114 comprises the following corrective action sites (CASs) located in Area 25 of the Nevada National Security Site: • 25-41-03, EMAD Facility (Building 3900) • 25-99-23, Manned Control Car (MCC) and Engine Installation Vehicle (EIV) • 25-33-05, Building 3901, Engine Transport System Maintenance Building (Train Shed) This plan provides the methodology for field activities needed to gather the necessary information for closing CAU 114. There is sufficient information and process knowledge from historical documentation and investigations of similar sites regarding the expected nature and extent of potential contaminants to recommend closure of CAU 114 using the SAFER process. Additional information will be obtained by conducting a field investigation before selecting the appropriate corrective actions for CAU 114. It is anticipated that the results of the field investigation and implementation of corrective actions will support a defensible recommendation that no further corrective action is necessary. The purpose of the corrective action investigation will be to document and verify the adequacy of existing information; to affirm the decision for either clean closure, closure in place, or no further action; and to provide sufficient data to implement the corrective action. The actual corrective action selected will be based on characterization activities implemented under this SAFER Plan. If specific conditions or findings fall outside the bounds of the conceptual site model, such as an unanticipated release, the Nevada Division of Environmental Protection (NDEP) will be consulted to determine the path forward before proceeding. Upon completion of SAFER activities, a closure report (CR) will be prepared and submitted to NDEP for review and approval. The schedule for completion of the CR will be established in consultation with NDEP.

54 ENVIRONMENTAL SCIENCES↗

Convergent Manufacturing of Large-Scale Components for Nuclear Applications, via Additive Manufacturing and Powder Metallurgy Hot Isostatic Pressing

Powder metallurgy (PM)–hot isostatic pressing (PM-HIP) has long been recognized as a powerful route for producing fully dense, near net shape metallic components. By consolidating powders under high temperature and pressure, HIP provides isotropic properties, uniform microstructures, and scalability to complex geometries that are vital for sectors such as aerospace, energy, and nuclear power. Yet despite these advantages, the technology has remained constrained by costly trial and error canister fabrication, limitations of conventional forging, and incomplete knowledge about how the canister design influences final part properties. Additive manufacturing (AM), by contrast, thrives on design freedom and geometric flexibility but struggles with speed, scalability, and cost when applied to very large structures. The research presented in this report investigated how a convergent manufacturing approach, combining AM with PM-HIP, can merge the strengths of both technologies, leveraging AM’s flexibility for canister design and HIP’s consolidation capability to deliver reliable, large, and complex parts. The work progressed through three case studies that built on one another in scale and complexity. Small cylindrical canisters fabricated by conventional methods, laser powder bed fusion, and directed energy deposition were filled with stainless steel powders and subjected to HIP. The resulting parts demonstrated near-full density and mechanical properties on par with wrought stainless steel, showing for the first time that AM canisters can be a direct substitute for conventional ones without sacrificing quality. The next step involved a medium-scale, noncentrosymmetric T-valve, which is an enclosed, multibranch geometry that tested the limits of AM + PM-HIP integration. The T-valve achieved predictable shrinkage and uniform densification, confirming feasibility for enclosed designs. However, this study also revealed oxide inclusions and interfacial challenges at the AM + HIP boundary, underscoring the critical importance of controlling interface chemistry and employing robust, in situ strategies, such as melt pool monitoring and thermal monitoring, coupled with nondestructive evaluation techniques such as x-ray computed tomography. Finally, the effort culminated in fabricating a large-scale impeller weighing nearly 2000 lb and spanning 5 ft in diameter. Produced via multirobot wire arc AM and hot isostatic pressed to near-full density, the impeller validated industrial-scale feasibility. Predictive models closely matched experimental shrinkage, tensile properties were spatially uniform across the component, and the AM + PM-HIP interface proved mechanically sound despite the presence of oxide-decorated prior particle boundaries. This large-scale demonstration is a major milestone, showing that hybrid AM + PM‑HIP can reliably deliver components at reactor-relevant scales. Collectively, these studies charted a logical pathway: small-scale work built scientific confidence, medium-scale work highlighted opportunities and challenges, and large-scale work proved industrial impact. The overarching conclusion of this report is that AM + PM-HIP should not be seen as a replacement for forging but as a complementary pathway that provides the US with flexibility, resilience, and new options for manufacturing nuclear-grade components. Looking ahead, several directions emerge as critical to sustaining progress. Predictive modeling must become faster, more accessible, and more accurate, with digital twins and machine learning reducing reliance on trial and error. Powders and alloys must be optimized for HIP, with improved cleanliness, reduced oxides, and tailored chemistries that enhance creep, fatigue, and irradiation resistance. Interfaces between AM and HIP regions must be better engineered through coatings, machining strategies, and surface treatments to mitigate oxide formation and ensure reliable bonding to explore opportunities for HIP of targeted compositional parts, as well as multimaterial HIP cladding applications. Monitoring and nondestructive evaluation need to expand, incorporating multimodal sensors, x-ray computed tomography, and real-time data integration through platforms such as Pelican. At the same time, the pathway to industrial adoption requires techno-economic analysis, machinability studies, and qualification frameworks aligned with industry and regulatory standards. Finally, workforce and academic engagement must be strengthened. Programs that train technicians and engineers for US Navy and US Department of Energy manufacturing challenges should be paired with academic partnerships to support fundamental research, with open sharing of non-export-controlled data to accelerate innovation and build the next generation of experts. In conclusion, this report demonstrates that hybrid AM + PM-HIP is scientifically viable and strategically important. By combining the design agility of AM with the consolidation strength of HIP and embedding modeling, monitoring, and workforce development, this approach provided a transformative new capability for US manufacturing. The path forward is clear: hybrid AM + PM-HIP is not just a promising research direction but is also potentially an industrially relevant pathway that can reshape how nuclear-grade components are designed, qualified, and deployed.

36 MATERIALS SCIENCE↗

Demonstration of Coupled Tiamat Single Assembly Calculations

This report corresponds to milestone L3:PHI.PCI.P15.03, which was originally intended to investigate the time discretization approaches with the newly developed fully coupled Tiamat capability, targeting single assembly problems. At the time, it was thought that various time discretization approaches would need to be assessed. However, it was decided that this was not necessary as what is currently implemented in the code is adequate to provide consistent and full coupling between MPACT, CTF, ORIGEN, and Bison. As such, the milestone has effectively been repurposed as a stepping stone to the quarter core demonstration milestone slated for completion in August by describing and demonstrating the new fully coupled Tiamat capability on a single assembly case based on VERA Progression Problem 6, but with the addition of depletion throughout a representative cycle. Additionally, several other contributions that have been critical to this demonstration are also described. These include (1) the 1.5D capability developed by the Bison team, (2) improvements to the burnup representation in Bison through Tiamat, and (3) the additions to MOOSE to allow Bison to resolve the same timestep are also discussed. Initial simulations have been performed for the Watts Bar Unit 1 Cycle 1 with fully coupled Tiamat. While there are a few things to be improved for the final simulations, the initial results look very promising. The current status and results from this will be presented here, as well as the path forward to resolve the issues observed.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Iodine Mass Tracking Research and Development Needs for Pyrochemical Fuel Cycles

This report was generated jointly by Argonne National Laboratory (ANL) and Idaho National Laboratory to provide a high-level summary of the current knowledge on the behavior of fission product iodine during reprocessing of used nuclear fuel, as well as provide recommended path forward for research and development activities to fill particular knowledge gaps. The focus of this work is on pyrochemical processing as is applied to light water reactor (LWR) oxide-based used nuclear fuels (UNF), however, some discussion of electrorefiner behavior from metal fuel processing equipment is also included.

11 - NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Proposed Classifications of Remote Operations for Nuclear Reactors Based on Physical and Cybersecurity Considerations

The incorporation of remote operations into reactor operations is a topic of high interest among advanced and small modular reactor (A/SMR) vendors, with some considering it essential to the success of their business models. However, remote operations are a concept novel to the nuclear industry. While various technical aspects of remote operations have been explored, a significant gap remains in understanding the security implications of integrating remote operations into reactor designs, particularly concerning the security requirements for remote-operations facilities and infrastructure. This report aims to address this gap by first defining classes of remote operation based on the extent of remote access to reactor control systems and grounded in the existing regulatory framework with compatible terminology. Secondly, the report outlines the physical and cybersecurity requirements applicable to remote-operations facilities and infrastructure at each defined class. These requirements are based on existing licensing frameworks provided by 10 Code of Federal Regulations (CFR) Part 50 and 10 CFR Part 52, as well as the upcoming A/SMR licensing framework in the proposed Part 53. The assessment focuses specifically on security regulations, such as 10 CFR Part 73, which includes provisions for both cybersecurity (§ 73.54) and physical security (§ 73.55). This report proposes five classes of remote reactor operations. Class 1 involves remote monitoring only, with no control over reactor systems. Class 2 allows for the remote issuance of allowlisted commands to the reactor facility. Class 3 extends control to non-safety-significant, non-safety-related, or not important to safety systems and equipment. Class 4 permits remote control of safety-significant systems. Finally, Class 5 allows remote control of safety-related systems. It is important to note that these classes were defined purely with functionality in mind, without considering the practicality or feasibility of implementation for each class under current or upcoming regulatory guidance. The intention behind this approach is to enable an assessment of which security requirements apply to each class, allowing readers to evaluate the implementation possibilities for their specific use cases. Following the definition of remote-operation classes, the report assesses the specific physical and cybersecurity requirements applicable to the remote-operations facility and infrastructure within each defined class. This includes defining the types and locations of operators that are possible at each class of operation and, based on operator type and location, as well as functionality within each class, outlining the physical and cybersecurity requirements. By detailing the security requirements by class, the report provides readers with the information needed to determine the type of security program they may need to implement for their desired concept of operation. The next contribution of this report was to assess the practicality of implementing each proposed class of remote operations based upon the security requirement assessment. In short, three of the five proposed remote-operation classes were found to possibly have a practical path forward to implementation under the U.S. regulatory framework. Class 1 remote operations are currently in use in the U.S. while Class 2 and 3 remote operations may be logistically possible to implement under the U.S. regulatory framework. The final two Classes, 4 and 5, would likely be logistically difficult, if not infeasible to implement within the current U.S. physical- and cybersecurity regulatory framework. Given the results of the feasibility assessment, an example architecture is proposed for both Class 2, remote allowlisted commands, and Class 3, remote control of non-safety systems as well as security implication assessments of each architecture. These example implementations are not meant to be prescriptive in terms of how Class 2 or Class 3 remote operations should be deployed; instead, they are intended to be informative to stakeholders on how Class 2 or Class 3 could potentially be applied in order to inform their system design. An example architecture for Class 1 remote monitoring was not provided as Class 1 in already in use in U.S. nuclear operations. Example architectures for Class 4 and Class 5 were not provided due to their assessment of being likely infeasible to implement. The final contribution is an assessment of the physical- and cybersecurity implications of introducing autonomous operations into an A/SMR. What was found was that the security implications can be separated into two cases. Autonomous operations supported by SSCs located only at the reactor site, and autonomous operations supported by SSCs outside of the reactor site. For the first case, the introduction of autonomous systems will likely not change the facility’s requirement to comply with existing cyber and physical security regulation

22 - GENERAL STUDIES OF NUCLEAR REACTORS↗

Development of a bench-scale dissolution concept for the direct extraction of nuclear fuel

Current used nuclear fuel reprocessing efforts utilize a hydrometallurgical approach in which the UNF is dissolved in hot nitric acid followed by solvent extraction into an organic solvent to harvest target nuclides. Previous studies have shown that the dissolution and loading process could be combined into a single organic dissolution/extraction step, producing loaded organic in a single step process. This single step process also includes the advantage of selectively targeting key nuclides in the dissolution while leaving undesirable constituents as part of the undissolved solids. This process is referred to hereafter as direct extraction. Ongoing research from multiple national labs has proven the effectiveness of this technique at research scale. Therefore, potential methods to implement direct extraction at both bench and industrial scale have been developed. The key features of potential dissolver system designs were identified via the team at Pacific Northwest National Laboratory and several designs based on industrial counterparts were assessed for feasibility. This report summarizes the advantages and disadvantages of multiple methods, concluding with a path forward to create multiple unique dissolver designs. The first design will be a single stage recirculating eductor mixer. The second design recommendation is a stator rotor static mixing flow loop design. Each dissolver could be utilized separately, simultaneously, or in series to answer questions surrounding reaction kinetics including residence time, provide a proof of concept for targeted extractions of specific nuclides, and inform needs for industrial scale implementation

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Optimization of wall assembly for DOE Efficient New Homes Program in HUD’s Climate Zones 2 and 3

Manufactured homes provide affordable housing for over 20 million Americans. The U.S. Department of Energy’s Efficient New Homes (ENH) program has introduced new energy certification requirements that manufacturers can optionally target to ensure outstanding levels of energy savings, comfort, health, and durability. In collaboration with Clayton Homes (under User Agreement (NN-23-1469)), Oak Ridge National Laboratory evaluated multiple wall assembly options to meet ENH requirements in HUD Climate Zones 2 and 3, with a target maximum cost premium of 5%. After analyzing thermal performance, cost, and manufacturability, insulated structural sheathing was identified as the most practical and effective solution. A full-scale manufactured home prototype demonstrated that this approach meets energy performance goals with minimal disruption to existing manufacturing processes and a cost premium of less than 10% with a path to further lower costs, offering a promising path forward for more efficient manufactured housing.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Testing the Common Platform LLRF with a 197 MHz NCRF Cavity

The Common Platform is the hardware that will support the new LLRF platform to be used for the Electron-Ion Collider. The Common Platform features a carrier board that is used to interface with a variety of daughter for different applications. This paper details the testing that was done using the Common Platform and an RF Digitizer Daugther Board. Firstly, the firmware and software development is discussed followed by a description of the controls algorithms used in the testing. Then, testing and verification of the platform with a 197 MHz NCRF cavity is discussed. The paper concludes with results from the testing and the path forward.

42 ENGINEERING↗

Toward Trustworthy Autonomous Science: A Two-Year Community Roadmap

One year ago, the AISLE roadmap argued that autonomous laboratories operated as isolated islands and proposed a grassroots network organized around five critical dimensions. The field has since moved faster than that roadmap anticipated: multi-agent systems have produced experimentally validated hypotheses, self-driving laboratories have grown more interoperable and orchestrated, reasoning-trained and domain foundation models have raised the capability ceiling, and the Genesis Mission has placed autonomous experimentation at the center of U.S. federal science strategy, with industry emerging as a primary actor. Progress has met a sobering counter-current, including a corrected flagship discovery result, benchmarks showing that agents which rival experts on closed-ended questions still complete only a fraction of open-ended research, and fabricated citations surfacing at leading venues. We read this as the defining tension of the field: producing a candidate discovery is no longer the hard part, but verifying it is, and this asymmetry now limits autonomous science more than raw model capability. Accordingly, we update the roadmap around seven dimensions, revisiting the original five and elevating two former cross-cutting concerns, trust, verification, and reproducibility, and safety, security, and governance, to first-class status. We assess the original milestones (M1 through M14) as achieved, partially achieved, reframed, or open, add four new milestones (M15 through M18) for the elevated dimensions, and scope the path forward to a two-year horizon, with the first year concentrating on interfaces, protocol adoption, and the scaffolding of verification, and the second targeting federation, zero-trust coordination, and governance. Throughout, we position the grassroots network as the interoperability fabric that lets national programs, international initiatives, and commercial platforms connect rather than re-silo.

99 GENERAL AND MISCELLANEOUS↗

PIP-II SRF Couplers Fabrication Status and Addressing Ceramic Yield Challenges

The PIP-II project requires reliable SRF couplers to deliver high RF power to the cavities. This talk presents the current status of coupler fabrication, including progress on procurement, assembly, and testing. In particular, it focuses on the challenges encountered with ceramic window production, where limited yield has become a concern. Observed issues and inspection results will be discussed, together with the actions taken to improve quality and consistency. The path forward, including ongoing work with vendors and process adjustments, will also be outlined.

Aiazzi, Tommaso [Fermilab] (ORCID:0009000297503407↗

Programmable Digital Devices used in Advanced Reactors

This paper introduces the concepts of common cause failure, diversity, and defense-in-depth used by the nuclear industry to analyze resilience in reactors. A survey of publicly traded and private companies building advanced reactors and their licensing status is presented. Safety and non-safety systems found in the NuScale Power design are summarized and the likely hardware and software categories used by those systems are enumerated. The importance of industry partners is highlighted. This paper also identifies an alternate path forward without industry partners to advance the knowledge needed to use artificial intelligence to analyze HBOMs and SBOMs to better understand reactor resiliency.

cybersecurity↗

The MAJORANA DEMONSTRATOR search for neutrinoless double beta decay

The MAJORANA Collaboration is constructing the MAJORANA DEMONSTRATOR, an ultra-low background, modular, HPGe detector array with a mass of 44.8-kg (29.7 kg enriched -88% in 76Ge) to search for neutrinoless double beta decay in 76Ge. The next generation of tonnescale Ge-based neutrinoless double beta decay searches will probe the neutrino mass scale in the inverted-hierarchy region. The MAJORANA DEMONSTRATOR is envisioned to demonstrate a path forward to achieve a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value of 2039 keV. The MAJORANA DEMONSTRATOR follows a modular implementation to be easily scalable to the next generation experiment. First data taken with the DEMONSTRATOR are introduced here.

Cuesta Soria, Clara↗

Local chiral EFT potentials in nuclei and neutron matter: results and issues

In recent years, the combination of advanced quantum Monte Carlo (QMC) methods and local interactions derived from chiral effective field theory (EFT) has been shown to provide a versatile and systematic approach to nuclear systems. Calculations at next-to-next-to-leading order in chiral EFT have lead to fascinating results for nuclei and nucleonic matter. On the one hand, ground-state properties of nuclei are well reproduced up to A $≤$ 16, even though these potentials have been fit to nucleon-nucleon scattering and few-body observables only. On the other hand, a reasonable description of neutron-matter properties emerges. While regulator functions applied to two- and three-nucleon forces are a necessary ingredient in these many-body calculations, the use of local regulators leads to a substantial residual regulator and cutoff dependence that increases current theoretical uncertainties. In this contribution, we review local chiral interactions, their applications, and QMC results for nuclei and neutron matter. In addition, we address regulator issues for such potentials and present a possible path forward.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Microemulsions: Breakthrough Electrolytes for Redox Flow Batteries

Aqueous and non-aqueous redox flow batteries (RFBs) have limited energy and current densities, respectively, due to the nature of the electrolytes. New approaches to electrolyte design are needed to improve the performance of RFBs. In this work, we combined a highly conductive aqueous phase and an organic redox-active phase in a microemulsion to formulate a novel RFB electrolyte. As a proof-of-concept, we demonstrate an RFB using this microemulsion electrolyte with maximum current density of 17.5 mA·cm −2 with a 0.19 M posolyte and 0.09 M negolyte at a flow rate of only ∼2.5 ml·min −1 , comparable to early vanadium electrolyte RFBs at similar flow rates on a per molar basis. The novel active negolyte component is an inexpensive oil-soluble vitamin (K 3 ). By combining aqueous and organic phases, the solvent potential window and energy density may be increased without sacrificing current density and new redox couples may be accessed. Microemulsion electrolytes show great promise for improved performance and increased energy densities in aqueous RFBs but the path forward is complex. We end with discussion of areas that need work to achieve the potential of these electrolytes.

25 ENERGY STORAGE↗

Parallelized, Aerobic, Single Carbon-Source Enrichments from Different Natural Environments Contain Divergent Microbial Communities

Microbial communities that inhabit environments such as soil can contain thousands of distinct taxa, yet little is known about how this diversity is maintained in response to environmental perturbations such as changes in the availability of carbon. By utilizing aerobic substrate arrays to examine the effect of carbon amendment on microbial communities taken from six distinct environments (soil from a temperate prairie and forest, tropical forest soil, subalpine forest soil, and surface water and soil from a palustrine emergent wetland), we examined how carbon amendment and inoculum source shape the composition of the community in each enrichment. Dilute subsamples from each environment were used to inoculate 96-well microtiter plates containing triplicate wells amended with one of 31 carbon sources from six different classes of organic compounds (phenols, polymers, carbohydrates, carboxylic acids, amines, amino acids). After incubating each well aerobically in the dark for 72 h, we analyzed the composition of the microbial communities on the substrate arrays as well as the initial inocula by sequencing 16S rRNA gene amplicons using the Illumina MiSeq platform. Comparisons of alpha and beta diversity in these systems showed that, while the composition of the communities that grow to inhabit the wells in each substrate array diverges sharply from that of the original community in the inoculum, these enrichment communities are still strongly affected by the inoculum source. We found most enrichments were dominated by one or several OTUs most closely related to aerobes or facultative anaerobes from the Proteobacteria (e.g., Pseudomonas, Burkholderia, and Ralstonia) or Bacteroidetes (e.g., Chryseobacterium). Comparisons within each substrate array based on the class of carbon source further show that the communities inhabiting wells amended with a carbohydrate differ significantly from those enriched with a phenolic compound. Selection therefore seems to play a role in shaping the communities in the substrate arrays, although some stochasticity is also seen whereby several replicate wells within a single substrate array display strongly divergent community compositions. Overall, the use of highly parallel substrate arrays offers a promising path forward to study the response of microbial communities to perturbations in a changing environment.

59 BASIC BIOLOGICAL SCIENCES↗

Transporter annotations are holding up progress in metabolic modeling

Mechanistic, constraint-based models of microbial isolates or communities are a staple in the metabolic analysis toolbox, but predictions about microbe-microbe and microbe-environment interactions are only as good as the accuracy of transporter annotations. A number of hurdles stand in the way of comprehensive functional assignments for membrane transporters. These include general or non-specific substrate assignments, ambiguity in the localization, directionality and reversibility of a transporter, and the many-to-many mapping of substrates, transporters and genes. In this perspective, we summarize progress in both experimental and computational approaches used to determine the function of transporters and consider paths forward that integrate both. Investment in accurate, high-throughput functional characterization is needed to train the next-generation of predictive tools toward genome-scale metabolic network reconstructions that better predict phenotypes and interactions. More reliable predictions in this domain will benefit fields ranging from personalized medicine to metabolic engineering to microbial ecology.

Casey, John↗