Mechanistic Approach Research Articles

Restoring forest ecosystem services through trait-based ecology

Restoration is moving towards a more mechanistic approach that emphasizes restoration of ecosystem services. Trait-based approaches provide links between species identity and ecosystem functions and have been suggested as a promising way to formally integrate ecosystem services in the design of restoration programs. While practitioners have been routinely using informal knowledge on plant traits in their practices, these approaches are underutilized as operationalization remains challenging. The goal of this paper is to provide guidance for applied scientists and restoration practitioners looking to apply a trait-based approach to restore forest ecosystems. We present a five-step framework: 1) selection of services to be restored, 2) trait selection, 3) data acquisition, 4) analytical planning, and 5) empirical testing and monitoring. We use three Canadian case studies to illustrate the applicability of our framework and the variety of ways trait-based approaches can inform restoration practices: 1) restoration of urban woodlots after an insect outbreak, 2) restoration of a smelter damaged landscape surrounding an urban area, and 3) reclamation of remote upland forests after oil and gas related disturbances. We describe the major mechanisms and traits that determine vegetation effects on ecosystem services of importance in each case study. We then discuss data availability, methodological constraints, comparability issues, analytical methods, and the importance of empirical testing and monitoring to ensure realistic prediction of service restoration. By outlining issues and offering practical information, we aim to contribute to a more robust use of traits in ecological restoration.

Calibrating payment for ecosystem services: a process-oriented policy design approach

Recent empirical research in policy design has shown the relevance of micro-level components, particularly specification and calibration, in shaping policy outcomes. Additionally, research highlights the importance that understanding the mechanisms underlying the policy process has for effective policy design. Yet, a gap persists in how to effectively calibrate and specify policies for specific cases, with a theoretical grounding and guidance for practitioners. This paper addresses this need by applying a process theory of change to delineate the key episodes that constitute the mechanisms of a plausible pathway for an effective Program for Ecosystem Services (PES), an incentives-based instrument focused on conserving forests producing carbon sequestration, biodiversity protection, and water infiltration, among other services. Specifically, the paper uses the well-documented Mexican PES to illustrate how to derive the mechanisms and use them for calibration and specification. The paper provides valuable theoretical insights drawn from the case study, contributing to the field of micro-policy design with a mechanistic approach.

Investigating effective strategies for sustainable operation of a submerged anaerobic membrane bioreactor (SAnMBR) coupled with ceramic ultrafiltration membrane

This study presents a mechanistic approach to explore the key operational parameters governing the flux performance of an SAnMBR system coupled with a ceramic flat-sheet ultrafiltration membrane. Experiments were conducted at mixed liquor suspended solid (MLSS) concentrations of 12, 18, and 24 g/L using biogas sparging, backwashing, and a combination of both to investigate the most effective fouling mitigation strategy by exploring the fouling mechanism at a critical flux regime. To validate the experimental findings, a mathematical model was used to simulate the time-based variation of membrane effective pore radius (m), decrease in membrane porosity (%), thickness of cake layer (m), and membrane resistance (1/m). The study found that at a low biomass concentration, there was a sharp decline in the membrane pore radius leading to an increase in membrane resistance in the absence of any fouling mitigation strategies. However, by implementing these strategies individually and in combination, they maintained a higher pore radius and controlled the increase in membrane resistance even at high biomass concentrations. It was observed that biogas sparging outperformed the conventional backwashing strategy and the SAnMBR system exhibited superior performance attaining higher flux rates for prolonged duration. The advanced spectroscopic analysis confirmed the presence of a higher concentration of polysaccharides responsible for cake layer biofouling, and significant pore blocking due to inorganic foulants at high biomass concentrations. This suggests that the SAnMBR system must be operated at optimised biomass levels below the critical flux for sustained operation. Additionally, the key operational parameters identified using the mathematical model provide a precise assessment of SAnMBR performance, to improve its design efficiency for field applications.

Towards Energy-Balance Closure with a Model of Dispersive Heat Fluxes

In the last decades the energy-balance-closure problem has been thoroughly investigated from different angles, resulting in approaches to reduce but not completely close the surface energy balance gap. Energy transport through secondary circulations has been identified as a major cause of the remaining energy imbalance, as it is not captured by eddy covariance measurements and can only be measured additionally with great effort. Several models have already been developed to close the energy balance gap that account for factors affecting the magnitude of the energy transport by secondary circulations. However, to our knowledge, there is currently no model that accounts for thermal surface heterogeneity and that can predict the transport of both sensible and latent energy. Using a machine-learning approach, we developed a new model of energy transport by secondary circulations based on a large data set of idealized large-eddy simulations covering a wide range of unstable atmospheric conditions and surface-heterogeneity scales. In this paper, we present the development of the model and show first results of the application on more realistic LES data and field measurements from the CHEESEHEAD19 project to get an impression of the performance of the model and how the application can be implemented on field measurements. A strength of the model is that it can be applied without additional measurements and, thus, can retroactively be applied to other eddy covariance measurements to model energy transport through secondary circulations. Our work provides a promising mechanistic energy balance closure approach to 30-min flux measurements.

Drug repurposing for diabetes mellitus: In silico and in vitro investigation of DrugBank database for α-glucosidase inhibitors

The process of developing novel compounds/drugs is arduous, time-intensive, and financially burdensome, characterized by a notably low success rate and relatively high attrition rates. To alleviate these challenges, compound/drug repositioning strategies are employed to predict potential therapeutic effects for DrugBank-approved compounds across various diseases. In this study, we devised a computational and enzyme inhibitory mechanistic approach to identify promising compounds from the pool of DrugBank-approved substances targeting Diabetes Mellitus (DM). Molecular docking analyses were employed to validate the binding interaction patterns and conformations of the screened compounds within the active site of α-glucosidase. Notably, Asp352 and Glu277 participated in interactions within the α-glucosidase-ligand complexes, mediated by conventional hydrogen bonding and van der Waals forces, respectively. The stability of the docked complexes (α-glucosidase-compounds) was scrutinized through Molecular Dynamics (MD) simulations. Subsequent in vitro analyses assessed the therapeutic potential of the repositioned compounds against α-glucosidase. Kinetic studies revealed that “Forodesine” exhibited a lower IC50 (0.24 ± 0.04 mM) compared to the control, and its inhibitory pattern corresponds to that of competitive inhibitors. In-depth in silico secondary structure content analysis detailed the interactions between Forodesine and α-glucosidase, unveiling significant alterations in enzyme conformation upon binding, impacting its catalytic activity. Overall, our findings underscore the potential of Forodesine as a promising candidate for DM treatment through α-glucosidase inhibition. Further validation through in vitro and in vivo studies is imperative to confirm the therapeutic benefits of Forodesine in conformational diseases such as DM.

Investigating the Roles of Protein on the Cobalt Alloy Surface Degradation for Biomedical Implant Through Tribocorrosion Mechanisms

Previous investigation has established the formation of tribofilm is influenced by tribochemical reactions between the electrolyte and the articulating surface of cobalt alloy through sliding tests in various simulated fluids. Although it has successfully characterized the film composition via spectroscopy analysis and indicated to have impact on material loss, a comprehensive understanding of the material degradation mechanism in tribocorrosion condition was still lacking. Therefore, this study aims to investigate the role of protein in the tribocorrosive degradation of cobalt-chromium-molybdenum (CoCrMo) alloy in different simulated physiological electrolytes. Using a similar testing protocol, tribocorrosion tests were conducted with reciprocating ceramic ball against CoCrMo samples immersed in saline and culture medium, compared to both electrolytes diluted with 25% fetal bovine serum (FBS). Synergistic and mechanistic approaches were employed to model the tribocorrosive degradation. Results reveal that protein plays a beneficial role in reducing corrosive (electrochemical) surface degradation under tribocorrosion condition, whilst increasing mechanical wear degradation in the process. Despite studies have shown that tribocorrosion behavior in metal alloys is highly influenced by the presence of organic matter, this study provides a more clarity of the roles played by protein in tribocorrosive degradation on CoCrMo surface as its novel finding.

Boosting N-Heterocyclic Carbene Radical Organocatalysis with Nickel Chemistry: A Rational Mechanistic Study-Based Approach

Boosting <i>N</i>-Heterocyclic Carbene Radical Organocatalysis with Nickel Chemistry: A Rational Mechanistic Study-Based Approach

Towards early diagnosis of Alzheimer's disease: advances in immune-related blood biomarkers and computational approaches.

Alzheimer's disease has an increasing prevalence in the population world-wide, yet current diagnostic methods based on recommended biomarkers are only available in specialized clinics. Due to these circumstances, Alzheimer's disease is usually diagnosed late, which contrasts with the currently available treatment options that are only effective for patients at an early stage. Blood-based biomarkers could fill in the gap of easily accessible and low-cost methods for early diagnosis of the disease. In particular, immune-based blood-biomarkers might be a promising option, given the recently discovered cross-talk of immune cells of the central nervous system with those in the peripheral immune system. Here, we give a background on recent advances in research on brain-immune system cross-talk in Alzheimer's disease and review machine learning approaches, which can combine multiple biomarkers with further information (e.g. age, sex, APOE genotype) into predictive models supporting an earlier diagnosis. In addition, mechanistic modeling approaches, such as agent-based modeling open the possibility to model and analyze cell dynamics over time. This review aims to provide an overview of the current state of immune-system related blood-based biomarkers and their potential for the early diagnosis of Alzheimer's disease.

Inactivation Mechanisms of Escherichia coli in Simulants of Respiratory and Environmental Aerosol Droplets

The airborne transmission of disease relies on the ability of microbes to survive aerosol transport and, subsequently, cause infection when interacting with a host. The length of time airborne microorganisms remain infectious in aerosol droplets is a function of numerous variables. We present measurements of mass and heat transfer from liquid aerosol droplets combined with airborne survival data for Escherichia coli MRE162, an ACDP category 1 microorganism used as a model system, under a wide range of environmental conditions, droplet compositions and microbiological conditions. In tandem, these companion measurements demonstrate the importance of understanding the complex relationship between aerosol microphysics and microbe survival. Specifically, our data consist of the correlation of a wide range of physicochemical properties (e.g., evaporation rates, equilibrium water content, droplet morphology, compositional changes in droplet solute and gas phase, etc.), with airborne viability decay to infer the impact of aerosol microphysics on airborne bacterial survival. Thus, a mechanistic approach to support prediction of the survival of microorganisms in the aerosol phase as a function of biological, microphysical, environmental, and experimental (aerosol-generation and sampling) processes is presented. Specific findings include the following: surfactants do not increase bacteria stability in aerosol, while both the bacteria growth phase and bacteria concentration may affect the rate at which bacteria decay in aerosol.

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding.

Through investigating the combined impact of the environmental exposures experienced by an individual throughout their lifetime, exposome research provides opportunities to understand and mitigate negative health outcomes. While current exposome research is driven by epidemiological studies that identify associations between exposures and effects, new frameworks integrating more substantial population-level metadata, including electronic health and administrative records, will shed further light on characterizing environmental exposure risks. Molecular biology offers methods and concepts to study the biological and health impacts of exposomes in experimental and computational systems. Of particular importance is the growing use of omics readouts in epidemiological and clinical studies. This paper calls for the adoption of mechanistic molecular biology approaches in exposome research as an essential step in understanding the genotype and exposure interactions underlying human phenotypes. A series of recommendations are presented to make the necessary and appropriate steps to move from exposure association to causation, with a huge potential to inform precision medicine and population health. This includes establishing hypothesis-driven laboratory testing within the exposome field, supported by appropriate methods to read across from model systems research to human.

Development of Mechanistic In Vitro-In Vivo Extrapolation to Support Bioequivalence Assessment of Long-Acting Injectables.

Long-acting injectable (LAI) formulations provide sustained drug release over an extended period ranging from weeks to several months to improve efficacy, safety, and compliance. Nevertheless, many challenges arise in the development and regulatory assessment of LAI drug products due to a limited understanding of the tissue response to injected particles (e.g., inflammation) impacting in vivo performance. Mechanism-based in silico methods may support the understanding of LAI-physiology interactions. The objectives of this study were as follows: (1) to use a mechanistic modeling approach to delineate the in vivo performance of DepoSubQ Provera® and formulation variants in preclinical species; (2) to predict human exposure based on the knowledge gained from the animal model. The PBPK model evaluated different elements involved in LAI administration and showed that (1) the effective in vivo particle size is potentially larger than the measured in vitro particle size, which could be due to particle aggregation at the injection site, and (2) local inflammation is a key process at the injection site that results in a transient increase in depot volume. This work highlights how a mechanistic modeling approach can identify critical physiological events and product attributes that may affect the in vivo performance of LAIs.

From growth inhibition to ultrastructural changes: Toxicological assessment of lambda cyhalothrin and fosetyl aluminium against Bacillus subtilis and Pseudomonas aeruginosa

In modern agricultural practices, agrochemicals and pesticides play an important role in protecting the crops from pests and elevating agricultural productivity. This strategic utilization is essential to meet global food demand due to the relentless growth of the world's population. However, the indiscriminate application of these substances may result in environmental hazards and directly affect the soil microorganisms and crop production. Considering this, an in vitro study was carried out to evaluate the pesticides' effects i.e. lambda cyhalothrin (insecticide) and fosetyl aluminum (fungicide) at lower, recommended, and higher doses on growth behavior, enzymatic profile, total soluble protein production, and lipid peroxidation of bacterial specimens (Pseudomonas aeruginosa and Bacillus subtilis). The experimental findings demonstrated a concentration-dependent decrease in growth of both tested bacteria, when exposed to fosetyl aluminium concentrations exceeding the recommended dose. This decline was statistically significant (p < 0.000). However, lambda cyhalothrin at three times of recommended dose induces 10% increase in growth of Pseudomonas aeruginosa (P. aeruginosa) and 76.8% decrease in growth of Bacillus subtilis (B. subtilis) respectively as compared to control. These results showed the stimulatory effect of lambda cyhalothrin on P. aeruginosa and inhibitory effect on B. subtilis. Pesticides induced notable alterations in biomarker enzymatic assays and other parameters related to oxidative stress among bacterial strains, resulting in increased oxidative stress and membrane permeability. Generally, the maximum toxicity of both (P. aeruginosa and B. subtilis) was shown by fosetyl aluminium, at three times of recommended dose. Fosetyl aluminium induced morphological changes like cellular cracking, reduced viability, aberrant margins and more damage in both bacterial strains as compared to lambda cyhalothrin when observed under scanning electron microscope (SEM). Conclusively the, present study provide an insights into a mechanistic approach of pyrethroid insecticide and phosphonite fungicide induced cellular toxicity towards bacteria.

Pongamia pinnata flowers powered Ag doped CuO nanoparticles for eco-friendly dye degradation and antimicrobial applications: a mechanistic approach

Pongamia pinnata flowers powered Ag doped CuO nanoparticles for eco-friendly dye degradation and antimicrobial applications: a mechanistic approach

Diet effects on ectotherm thermal performance.

The environment is changing rapidly, and considerable research is aimed at understanding the capacity of organisms to respond. Changes in environmental temperature are particularly concerning as most animals are ectothermic, with temperature considered a key factor governing their ecology, biogeography, behaviour and physiology. The ability of ectotherms to persist in an increasingly warm, variable, and unpredictable future will depend on their nutritional status. Nutritional resources (e.g. food availability, quality, options) vary across space and time and in response to environmental change, but animals also have the capacity to alter how much they eat and what they eat, which may help them improve their performance under climate change. In this review, we discuss the state of knowledge in the intersection between animal nutrition and temperature. We take a mechanistic approach to describe nutrients (i.e. broad macronutrients, specific lipids, and micronutrients) that may impact thermal performance and discuss what is currently known about their role in ectotherm thermal plasticity, thermoregulatory behaviour, diet preference, and thermal tolerance. We finish by describing how this topic can inform ectotherm biogeography, behaviour, and aquaculture research.

Development of phytosterol-loaded silver nanoparticles for ameliorating haemorrhoidal complications via the AMPK pathway—a mechanistic approach

The aim of the current study was to synthesize silver nanoparticles (PLSNPs) using green technology by means of phytosterol-enriched fractions from Blumea lacera extracts (EAF) and evaluate their toxicological and anti-haemorrhoidal potential. The average size of the synthesized particles was found to be 85.64 nm by scanning electron microscopy and transmission electron microscopy. Energy dispersive spectroscopy showed the elemental composition of PLSNPs to be 12.59% carbon and 87.41% silver, indicating the capping of phytochemicals on the PLSNPs. The PLSNPs were also standardized for total phytosterol content using chemical methods and high-perfromance liquid chromatography. The PLSNPs were found to be safe up to 1000 mg kg−1 as no toxicity was observed in the acute and sub-acute toxicity studies performed as per OECD guidelines. After the induction of haemorrhoids, experimental animals were treated with different doses of EAF, PLSNPs and a standard drug (Pilex) for 7 d, and on the eighth day the ameliorative potential was assessed by evaluating the haemorrhoidal (inflammatory severity index, recto-anal coefficient) and biochemical (tumour necrosis factor-alpha and interleukin-6) parameters and histology of the recto-anal tissue. The results showed that treatment with PLSNPs and Pilex significantly (p < 0.05) reduced haemorrhoidal and biochemical parameters. This was further supported by restoration of altered antioxidant status. Further, a marked reduction in the inflammatory zones along with minimal dilated blood vessels was observed in the histopathological study. The results of molecular docking studies also confirmed the amelioration of haemorrhoids via AMP-activated protein kinase (AMPK)-mediated reduction of inflammation and endothelin B receptor modification by PLSNPs. In conclusion, PLSNPs could be a good alternative for the management of haemorrhoids.

Mechanistic Approach Toward the C4‐Selective Amination of Pyridines via Nucleophilic Substitution of Hydrogen

The development of site‐selective functionalization of N‐heteroarenes is highly desirable in streamlined synthesis. In this context, direct amination of pyridines stands as an important synthetic methodology, with particular emphasis on accessing 4‐aminopyridines, a versatile pharmacophore in medicinal chemistry. Herein, we report a reaction manifold for the C4‐selective amination of pyridines by employing nucleophilic substitution of hydrogen (SNH). Through 4‐pyridyl pyridinium salt intermediates, 4‐aminopyridine products are obtained in reaction with aqueous ammonia without intermediate isolation. The notable regioselectivity was achieved by the electronic tuning of the external pyridine reagents along with maximization of polarizability in the proton elimination stage. Further mechanistic investigations provided a guiding principle for the selective C–H pyridination of additional N‐heteroarenes, presenting a strategic avenue for installation of diverse functional groups.

The Association Between Self-Surveillance and Self-Rated Health in College Women: A Mechanistic Approach

Although women outlive men, women report poorer self-rated physical health over much of the lifespan. Objectification theory may offer insight into this gender difference. Objectifying culture promotes self-surveillance, which encourages prioritizing the body’s appearance over its physical functioning and well-being. As women may engage in self-surveillance more so than men, this sequence of events may help explain this gender difference in self-rated health. However, the few studies examining this idea show an inconsistent relationship between self-surveillance and self-rated health. Nonetheless, self-surveillance may promote body shame and diminished awareness of internal bodily states. As these factors are associated with poor self-rated health, self-surveillance may predict poor self-rated health via these mechanisms. In study 1 ( N = 166 undergraduate women), self-surveillance was unrelated to self-rated health. However, body shame and low interoceptive awareness mediated this relationship. In study 2 ( N = 347 undergraduate women and men), self-surveillance correlated negatively with self-rated health for female participants but not male participants. Female participants reported poorer self-rated health, and this effect was serially mediated by self-surveillance, body shame, and low body responsiveness. These studies suggest a potential avenue by which self-surveillance may explain the gender difference in self-rated health in college samples, providing an important basis for future longitudinal investigations in more diverse samples. Moreover, these results suggest that interventions targeting body shame and low internal awareness may be used to promote good self-rated health as well as to prevent disease and poor health behaviors related to self-rated health.

Abstract SY03-03: Thinking outside the chromosome: Interrogating epigenetic mechanisms in noncanonical chromatin species

Abstract The epigenetic regulation of DNA-templated processes is intricately tied to numerous events that determine cell phenotype and fate. The abrogation of epigenetic cascades drives various disease states, including cancer. Many of these pathological phenomena involve major chromosomal arrangements that can include the generation of non-canonical chromatin structures existing in the primary nuclei or encapsulated in spatially distinct micronuclei. Recently, we undertook a mechanistic approach to investigate the properties of unique non-chromosomal structures, revealing significant epigenetic contributions to their regulation. We found that micronuclei, the result of chromosomal instability in cancer, assume altered epigenetic landscapes upon departure from the nucleus. Moreover, chromosomes sequestered in micronuclei retain the epigenetic "scars" after reintegration into the primary nucleus, contributing to epigenetic reprogramming and heterogeneity in cancer. Additionally, we turned our attention to the Hepatitis B Virus' (HBV) covalently closed circular DNA (cccDNA) minichromosome, which forms from viral DNA and human histones following infection. We found that chromatinization drives the expression of the key viral oncogene, HBx, and thus promotes viral infection. Elucidating this new mechanism enabled us to halt infection by inhibiting histone remodeling, creating a potential first-in-class therapy for HBV. These exciting findings demonstrate the key role of chromatin in biomedical events and how a fundamental understanding of these processes can lead to the identification of new therapeutic avenues. Citation Format: Yael David. Thinking outside the chromosome: Interrogating epigenetic mechanisms in noncanonical chromatin species [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr SY03-03.

A mechanistic alternative to minimal sufficiency as the guiding principle for NCC research.

A central project for the neuroscience of consciousness is to reveal the neural basis of consciousness. For the past 20-odd years, this project has been conceptualized in terms of minimal sufficiency. Recently, a number of authors have suggested that the project is better conceived in mechanistic terms as the search for difference-makers. In this paper, I (i) motivate this mechanistic alternative to minimal sufficiency, (ii) develop it further by clarifying debates about the prospects of leveraging mutual manipulability to distinguish constitutive difference-makers from those that are merely causal, and (iii) explore the implications this has for recent debates concerning the status of the prefrontal cortex. I argue that adopting a mechanistic approach to the neuroscience of consciousness suggests that the prefrontal cortex is part of the neural mechanisms underlying consciousness even if it is not strictly speaking a necessary part.

Abstract LB006: Cell marker-based classification of TNBC subtypes and patient outcomes

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive BC subtype characterized by significant molecular and clinical heterogeneity, influenced by genetic, phenotypic, and environmental factors, as well as interactions of the tumor with its surrounding milieu. In the recent past, gene expression-based subtyping methods have provided a functional understanding for the observed molecular diversity/heterogeneity. In this study, we propose an approach to reclassifying TNBC while considering the cellular heterogeneity of the tumor as well as the tumor milieu. Methods: RNA-Sequencing data for TNBC cohort of 250 diverse women [European (EA, self-reported race, SRR): 114 and African (AA, SRR): 136)], was obtained from our collaborators at LSUHSC. 38/250 were labeled ERhi via IHC but histologically confirmed to be TNBC patients. We utilized 261 breast specific cell type markers to classify our cohort via hierarchical (HC) and consensus (CC) clustering. Differentially expressed genes (DEGs) were identified at p-adj ≤ 0.05. Endotype specific networks were generated using protein-protein interactions, DEGs, and genes regulated by transcription factor. Survival was assessed via log-rank tests. Genetic admixture was performed on 227/250 patients using method described by Pakstis, A. J. et al. Results: We identified three distinct mechanistic subtypes (endotype, CC1-3) containing nine distinct groups (HC1-9), revealing substantial heterogeneity in cell-type and tissue-state within TNBC. Each subtype exhibited unique biomarkers, reflecting diverse immune, extracellular matrix, adipogenesis, and inflammatory signatures. Endotype specific networks revealed patients in CC1 exhibited upregulation of CD8 T cell activation, interferon and interleukin markers, while CC2 showed upregulation of extracellular matrix genes, and CC3, the subtype containing ERhi patients, showed upregulation of fatty acid regulation, hormone sensitivity, and pro-inflammatory genes. Survival analysis demonstrated favorable outcomes for CC1 and less favorable outcomes for CC2. Additionally, SRR-inferred survival differences highlighted poorer outcomes for CC2 groups. We found SRR-inferred prognostic biomarkers such as TTC6, ANKRD30A, and KRT86 associated with distinct prognostic profiles in CC2. Genetic admixture showed a comparable distribution of SRR and genetic ancestry across subtypes. We developed a user-friendly Shiny App for our subtyping method and validated it using TCGA TNBC data. Conclusion: TNBC subtyping using cellular heterogeneity of biopsied samples provides a mechanistic approach to patient classification. Subtype-specific mechanisms suggest tailored therapeutic strategies and provide survival outcomes specific to each subtype. Our method can be applied to other cohorts using the application developed in this work. Citation Format: Zahra Mesrizadeh, Kavitha Mukund, Fokrul Hossain, Jovanny Zabaleta, Denise Danos, Luis Del Valle, Xiao-Cheng Wu, Chindo Hicks, Yuan Chun Ding, Augusto Ochoa, Lucio Miele, Victoria L. Seewaldt, Shankar Subramaniam. Cell marker-based classification of TNBC subtypes and patient outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB006.