Journal articles on the topic 'Endogenous Dimensionality'

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1

McCloskey, M. A., and M. M. Poo. "Rates of membrane-associated reactions: reduction of dimensionality revisited." Journal of Cell Biology 102, no. 1 (January 1, 1986): 88–96. http://dx.doi.org/10.1083/jcb.102.1.88.

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The hypothesis that reactions associated with intracellular membranes enjoy a kinetic advantage from a reduced dimensionality for diffusion is inconsistent with available data on lateral diffusion rates, membrane-substrate affinities, and endogenous concentrations of enzymes and their aqueous substrates.
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2

Sthijns, Mireille M. J. P. E., Timo Rademakers, Jolien Oosterveer, Thomas Geuens, Clemens A. van Blitterswijk, and Vanessa L. S. LaPointe. "The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress." PLOS ONE 17, no. 3 (March 15, 2022): e0257578. http://dx.doi.org/10.1371/journal.pone.0257578.

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The pancreatic islets of Langerhans have low endogenous antioxidant levels and are thus especially sensitive to oxidative stress, which is known to influence cell survival and behaviour. As bioengineered islets are gaining interest for therapeutic purposes, it is important to understand how their composition can be optimized to diminish oxidative stress. We investigated how the ratio of the two main islet cell types (alpha and beta cells) and their culture in three-dimensional aggregates could protect against oxidative stress. Monolayer and aggregate cultures were established by seeding the alphaTC1 (alpha) and INS1E (beta) cell lines in varying ratios, and hydrogen peroxide was applied to induce oxidative stress. Viability, oxidative stress, and the level of the antioxidant glutathione were measured. Both aggregation and an increasing prevalence of INS1E cells in the co-cultures conferred greater resistance to cell death induced by oxidative stress. Increasing the prevalence of INS1E cells also decreased the number of alphaTC1 cells experiencing oxidative stress in the monolayer culture. In 3D aggregates, culturing the alphaTC1 and INS1E cells in a ratio of 50:50 prevented oxidative stress in both cell types. Together, the results of this study lead to new insight into how modulating the composition and dimensionality of a co-culture can influence the oxidative stress levels experienced by the cells.
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3

Khalil, Muhammad Hassan, Li Jie, and Jia Dong Xu. "Mathematical Analysis of Microwave Tomography: The Reconstruction Problem of Malignant Tumor." Applied Mechanics and Materials 332 (July 2013): 527–33. http://dx.doi.org/10.4028/www.scientific.net/amm.332.527.

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Early breast cancer detection is an emerging field of research as it can save many lives infected by malignant tumors. Microwave imaging is one of the main pillars in biomedical fields of comprehensive cancer care. The mathematical theory of microwave tomography involves solving an image reconstruction problem for Maxwell’s equations. In this research contribution, we analyze the potential of an image reconstruction model for the early detection of breast tumors from microwave tomography method. The detection of early-stage tumors within the breast by microwave tomography imaging is challenged by both the moderate endogenous dielectric contrast between healthy and malignant glandular tissues and the spatial resolution available from illumination at microwave frequencies. The formulation as a shape-reconstruction problem offers several advantages compared to more traditional pixel-based schemes, to mention, in particular, well defined boundaries and the incorporation of an intrinsic regularization that reduces the dimensionality of the inverse problem whereby at the same time stabilizing the reconstruction. We present in this paper a novel strategy that can detect very small tumors compared to the wavelength used for illuminating the breast. In addition, our algorithm can determine the sizes and the dielectric properties of the tumors with good accuracy.
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Chernozhukov, Victor, Iván Fernández-Val, Whitney Newey, Sami Stouli, and Francis Vella. "Semiparametric estimation of structural functions in nonseparable triangular models." Quantitative Economics 11, no. 2 (2020): 503–33. http://dx.doi.org/10.3982/qe1239.

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Triangular systems with nonadditively separable unobserved heterogeneity provide a theoretically appealing framework for the modeling of complex structural relationships. However, they are not commonly used in practice due to the need for exogenous variables with large support for identification, the curse of dimensionality in estimation, and the lack of inferential tools. This paper introduces two classes of semiparametric nonseparable triangular models that address these limitations. They are based on distribution and quantile regression modeling of the reduced form conditional distributions of the endogenous variables. We show that average, distribution, and quantile structural functions are identified in these systems through a control function approach that does not require a large support condition. We propose a computationally attractive three‐stage procedure to estimate the structural functions where the first two stages consist of quantile or distribution regressions. We provide asymptotic theory and uniform inference methods for each stage. In particular, we derive functional central limit theorems and bootstrap functional central limit theorems for the distribution regression estimators of the structural functions. These results establish the validity of the bootstrap for three‐stage estimators of structural functions, and lead to simple inference algorithms. We illustrate the implementation and applicability of all our methods with numerical simulations and an empirical application to demand analysis.
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5

Potenza, Alessia, Chiara Balestrieri, Luca Albarello, Federica Pedica, Lorena Stasi, Francesco Manfredi, Martina Spiga, et al. "Abstract 567: CRISPR/Cas9-mediated CD39 disruption can be combined with TCR editing in T cells to improve the adoptive T cell therapy of colorectal cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 567. http://dx.doi.org/10.1158/1538-7445.am2022-567.

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Abstract Colorectal cancer (CRC) is the 2nd cause of cancer-related death. Despite standard therapies, more than 50% of patients experience relapse, eventually with metastatic disease. The CRC microenvironment is densely infiltrated by T-cells, which presence correlates with improved overall survival, thus sustaining the rational for immunotherapy. Here, we paired high-dimensional flow cytometry, bulk RNA sequencing and immunohistochemistry to describe the phenotype and the exhaustion status of T-cells infiltrating primary and metastatic CRC. Analysis of the healthy, peritumoral and neoplastic tissues of treatment-naïve primary CRCs and of the peritumoral and tumoral tissues of CRC patients undergoing surgery for liver metastasis, revealed extensive transcriptional and spatial remodeling across tumors. Unsupervised analysis of flow cytometry data performed by an advanced pipeline of data handling by dimensionality reduction and clustering algorithms allowed the definition of a peculiar inhibitory receptors signature on TILs enriched both in primary CRCs and liver metastases. Of note, CD39 was upregulated in both the signatures retrieved from primary and metastatic CRC, thus suggesting its relevance as molecular target for T-cells engineering. By CRISPR/Cas9 we disrupted the CD39 gene in T cells with >80% efficiency. We combined CD39 knock-out with the genetic disruption of alpha and beta chains of the endogenous TCR, observing >90% efficiency for both genes, thus generating triple-knockout T-cells. By repetitively stimulating healthy donors’ peripheral blood mononuclear cells with autologous antigen-presenting cells loaded with a pool of peptides selected to be immunogenic and expressed by CRC, we obtained a library of anti-tumor TCRs to redirected the specificity of triple knock-out lymphocytes. Our preliminary experiments showed a functional advantage for TCR-redirected, CD39 disrupted T-cells in recognizing and killing CRC target cells. Citation Format: Alessia Potenza, Chiara Balestrieri, Luca Albarello, Federica Pedica, Lorena Stasi, Francesco Manfredi, Martina Spiga, Elena Tassi, Beatrice Claudia Cianciotti, Danilo Abbati, Ugo Elmore, Andrea Biondi, Luca Aldrighetti, Claudia De Lalla, Giulia Di Lullo, Paolo Dellabona, Eliana Ruggiero, Riccardo Rosati, Chiara Bonini. CRISPR/Cas9-mediated CD39 disruption can be combined with TCR editing in T cells to improve the adoptive T cell therapy of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 567.
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6

Kabraji, Sheheryar Kairas, Giorgio Gaglia, Danae Argyropoulou, Yang Dai, Shu Wang, Johann Bergholz, Shannon Coy, et al. "Temporal and spatial topography of cell proliferation in cancer." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 3122. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.3122.

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3122 Background: Tumors are complex ecosystems where exogenous and endogenous cues are integrated to either stimulate or inhibit cancer cell proliferation. However, the nature of these complex cell cycle states, their spatial organization, response to perturbation, and implications for clinical outcomes, are poorly characterized in tumor tissues. Methods: We used multiplexed tissue imaging to develop a robust classifier of proliferation, the multivariate proliferation index (MPI), using 513 unique tumors across five cancer types. Next, we used dimensionality reduction analysis to assess how the patterns of cell cycle protein expression in tumors were altered in response to perturbation. Results: The MPI outperforms single markers, like Ki67, when classifying proliferative index across diverse tumor types and reveals the proliferative architecture of tumors in situ. We find that proliferative and non-proliferative cancer cells are organized across microscopic (cell-to-cell) and macroscopic (tissue-level) scales. Both domains are reshaped by therapy, and local clusters of proliferative and non-proliferative tumor cells preferentially neighbor distinct tumor-infiltrating immune cells. We further phenotyped non-proliferating cancer cells using markers of quiescent cancer cells, cancer stem cells, and dormant cancer cells. We found that these types of non-proliferating cancer cells can occupy distinct regions within the same primary tumor. In high-dimensional marker space, populations of proliferative cancer cells express canonical patterns of cell cycle protein markers, a property we refer to as “cell cycle coherence”. Untreated tumors exist in a continuum of coherence states, ranging from optimal coherence, akin to freely cycling cells in culture, to reduced coherence characterized by either cell cycle polarization or non-canonical marker expression. Coherence can be stereotypically altered by induction and abrogation of mitogen signaling in a HER2-driven model of breast cancer. Cell cycle coherence is modulated by neoadjuvant therapy in patients with localized breast cancer, and coherence is associated with disease-free survival after adjuvant therapy in patients with colorectal cancer, mesothelioma and glioblastoma. Conclusions: The MPI robustly defines proliferating and non-proliferating cells in tissues, with immediate implications for clinical practice and research. The coherence metrics capture the diversity of post-treatment cell cycle states directly in clinical samples, a fundamental step in advancing precision medicine. More broadly, replacing binary metrics with multivariate traits provides a quantitative framework to study temporal processes from fixed static images and to investigate the rich spatial biology of human cancers.
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7

Butt, Umer Javed, Imam Hassouna, Laura Fernandez Garcia-Agudo, Agnes A. Steixner-Kumar, Constanze Depp, Nadine Barnkothe, Matthias R. Zillmann, et al. "CaMKIIα Expressing Neurons to Report Activity-Related Endogenous Hypoxia upon Motor-Cognitive Challenge." International Journal of Molecular Sciences 22, no. 6 (March 20, 2021): 3164. http://dx.doi.org/10.3390/ijms22063164.

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We previously introduced the brain erythropoietin (EPO) circle as a model to explain the adaptive ‘brain hardware upgrade’ and enhanced performance. In this fundamental circle, brain cells, challenged by motor-cognitive tasks, experience functional hypoxia, triggering the expression of EPO among other genes. We attested hypoxic cells by a transgenic reporter approach under the ubiquitous CAG promoter, with Hif-1α oxygen-dependent degradation-domain (ODD) fused to CreERT2-recombinase. To specifically focus on the functional hypoxia of excitatory pyramidal neurons, here, we generated CaMKIIα-CreERT2-ODD::R26R-tdTomato mice. Behavioral challenges, light-sheet microscopy, immunohistochemistry, single-cell mRNA-seq, and neuronal cultures under normoxia or hypoxia served to portray these mice. Upon complex running wheel performance as the motor-cognitive task, a distinct increase in functional hypoxic neurons was assessed immunohistochemically and confirmed three-dimensionally. In contrast, fear conditioning as hippocampal stimulus was likely too short-lived to provoke neuronal hypoxia. Transcriptome data of hippocampus under normoxia versus inspiratory hypoxia revealed increases in CA1 CaMKIIα-neurons with an immature signature, characterized by the expression of Dcx, Tbr1, CaMKIIα, Tle4, and Zbtb20, and consistent with accelerated differentiation. The hypoxia reporter response was reproduced in vitro upon neuronal maturation. To conclude, task-associated activity triggers neuronal functional hypoxia as a local and brain-wide reaction mediating adaptive neuroplasticity. Hypoxia-induced genes such as EPO drive neuronal differentiation, brain maturation, and improved performance.
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8

Hough, Michelle, Michael Fenlon, Alison Glazier, Celia Short, Gerardo Esteban Fernandez, Jiabo Xu, Elaa Mahdi, Kinji Asahina, and Kasper S. Wang. "Urea-based amino sugar agent clears murine liver and preserves protein fluorescence and lipophilic dyes." BioTechniques 70, no. 2 (February 2021): 72–80. http://dx.doi.org/10.2144/btn-2020-0063.

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Five established clearing protocols were compared with a modified and simplified method to determine an optimal clearing reagent for three-dimensionally visualizing fluorophores in the murine liver, a challenging organ to clear. We report successful clearing of whole liver lobes by modification of an established protocol (UbasM) using only Ub-1, a urea-based amino sugar reagent, in a simpler protocol that requires only a 24-h processing time. With Ub-1 alone, we observed sufficiently preserved liver tissue structure in three dimensions along with excellent preservation of fluorophore emissions from endogenous protein reporters and lipophilic tracer dyes. This streamlined technique can be used for 3D cell lineage tracing and fluoroprobe-based reporter gene expression to compare various experimental conditions.
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9

Ulanowicz, Robert E. "Process Ecology: Philosophy Passes into Praxis." Process Studies 45, no. 2 (October 1, 2016): 199–222. http://dx.doi.org/10.2307/44798505.

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Abstract Mechanical reductionism, which deals entirely with homogeneous variables, will constrain and enable the activities of richly heterogeneous living systems, but it cannot determine their outcomes. Such indeterminism owes to problems with dimensionality, dynamical logic, intractability, and insufficiency. The order in any living structure arises via an historical series of contingencies that were selected endogenously by stable autocatalytic processes in tandem with, and usually in opposition to, conventional external influences (natural selection). The development of living communities thereby resembles a Heraclitean dialectic between processes that build up and those that tear down. Investigating this unconventional dynamic requires metaphysical assumptions that are complementary to those that have guided science over the past three centuries. The new dynamics can be represented in terms of weighted networks of interacting processes, which facilitate the statement of testable hypotheses. Network analysis thereby implements and tests ideas that heretofore could only be addressed as verbal propositions.
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10

Parker, Gordon, and Dusan Hadzi-Pavlovic. "Old data, new interpretation: a re-analysis of Sir Aubrey Lewis' M.D. thesis." Psychological Medicine 23, no. 4 (November 1993): 859–70. http://dx.doi.org/10.1017/s0033291700026349.

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SynopsisSir Aubrey Lewis studied 61 depressives in considerable detail, principally cross-sectionally but also by reviewing progress. He concluded that he could find no qualitative distinctions between the depressed patients and thus established himself as a strong and influential advocate of the unitary view of depression (i.e. that depression varies dimensionally, not categorically). Subsequently, Kiloh & Garside (proponents of the binary view of two depressive ‘types’) coded the Lewis data and undertook a principal components analysis. They claimed success in distinguishing ‘endogenous’ and ‘neurotic’ depressive types within Lewis' sample. In this paper we re-analyse the data set using both a latent class categorical approach and mixture analyses. We suggest that any demonstration of sub-types was limited by relative homogeneity of the sample (in that up to 80% had probable or possible psychotic conditions), and by Lewis rating a number of important features (e.g. delusions) dimensionally rather than categorically. Nevertheless, we identify one categorical class (essentially an agitated psychotic depressive condition) and a residual (presumably heterogeneous) class. The presence of those two classes was supported by demonstrating bimodality in composite scores derived from the fourteen differentiating clinical features (and not evident when all clinical features were considered), and formally confirmed by mixture analyses. Membership of the categorical class was determined principally by psychotic features (delusions and hallucinations) and by objectively-judged psychomotor disturbance, and we consider the nature of that ‘class’. Lewis' data set is unusual (in having self-report and observationally rated data), and historically important in demonstrating that conclusions may depend on the choice of variables examined and analytical approaches.
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11

Kirchner, William, and Steve Southward. "Real-Time Estimation of Endogenous and Exogenous Inputs." Journal of Dynamic Systems, Measurement, and Control 136, no. 4 (March 13, 2014). http://dx.doi.org/10.1115/1.4026473.

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Nearly all dynamic systems have input excitations that are either unmeasurable or unknown due to practical constraints such as feasibility or cost. Estimation of these excitations can be useful both in control applications as well as system modeling applications. The objective of this work is to expand upon an observer based approach to estimate unmeasurable or unknown inputs to a dynamic system using linear systems theory in an efficient manner that is suitable for real-time implementation. In this work, we explicitly explore two fundamental questions. How should the structure, dimensionality, and parameterization of an internal model or waveform generator model be selected for a given dynamic system? How do we determine, based on the structure of the dynamic system, whether estimation of exogenous and endogenous inputs is possible? A series of numerical simulations is performed, providing insight into these issues.
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12

Guo, Hui, and Weisheng Lu. "Measuring competitiveness with data-driven principal component analysis: a case study of Chinese international construction companies." Engineering, Construction and Architectural Management, February 1, 2022. http://dx.doi.org/10.1108/ecam-04-2020-0262.

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Purpose Defining and measuring competitiveness has been a major focus in the business and competition literature over the past decades. The paper aims to use data-driven principal component analysis (PCA) to measure firm competitiveness. Design/methodology/approach A “3Ps” (performance, potential, and process) firm competitiveness indicator system is structured for indicator selection. Data-driven PCA is proposed to measure competitiveness by reducing the dimensionality of indicators and assigning weights according to the endogenous structure of a dataset. To illustrate and validate the method, a case study applying to Chinese international construction companies (CICCs) was conducted. Findings In the case study, 4 principal components were derived from 11 indicators through PCA. The principal components were labeled as “performance” and “capability” under the two respective super-components of “profitability” and “solvency” of a company. Weights of 11 indicators were then generated and competitiveness of CICCs was finally calculated by composite indexes. Research limitations/implications This study offers a systematic indicator framework for firm competitiveness. The study also provides an alternative approach to better solve the problem of firm competitiveness measurement that has long plagued researchers. Originality/value The data-driven PCA approach alleviates the difficulties of dimensionality and subjectivity in measuring firm competitiveness and offers an alternative choice for companies and researchers to evaluate business success in future studies.
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13

Jappe, Emma C., Christian Garde, Sri H. Ramarathinam, Ethan Passantino, Patricia T. Illing, Nicole A. Mifsud, Thomas Trolle, Jens V. Kringelum, Nathan P. Croft, and Anthony W. Purcell. "Thermostability profiling of MHC-bound peptides: a new dimension in immunopeptidomics and aid for immunotherapy design." Nature Communications 11, no. 1 (December 2020). http://dx.doi.org/10.1038/s41467-020-20166-4.

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AbstractThe features of peptide antigens that contribute to their immunogenicity are not well understood. Although the stability of peptide-MHC (pMHC) is known to be important, current assays assess this interaction only for peptides in isolation and not in the context of natural antigen processing and presentation. Here, we present a method that provides a comprehensive and unbiased measure of pMHC stability for thousands of individual ligands detected simultaneously by mass spectrometry (MS). The method allows rapid assessment of intra-allelic and inter-allelic differences in pMHC stability and reveals profiles of stability that are broader than previously appreciated. The additional dimensionality of the data facilitated the training of a model which improves the prediction of peptide immunogenicity, specifically of cancer neoepitopes. This assay can be applied to any cells bearing MHC or MHC-like molecules, offering insight into not only the endogenous immunopeptidome, but also that of neoepitopes and pathogen-derived sequences.
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14

Bu, Wenhuan, Yuanhao Wu, Amir M. Ghaemmaghami, Hongchen Sun, and Alvaro Mata. "Rational design of hydrogels for immunomodulation." Regenerative Biomaterials, February 22, 2022. http://dx.doi.org/10.1093/rb/rbac009.

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Abstract The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development, repair, and regeneration. Traditional immunomodulatory biologics exhibit limitations including degradation by enzymes, short half-life, and lack of targeting ability. Encapsulating or binding these biologics within biomaterials is an effective way to address these problems. Hydrogels are promising immunomodulatory materials because of their prominent biocompatibility, tuneability, and versatility. However, to take advantage of these opportunities and optimize material performance, it is important to more specifically elucidate, and leverage on, how hydrogels affect and control the immune response. Here, we summarize how key physical and chemical properties of hydrogels affect the immune response. We first provide an overview of underlying steps of the host immune response upon exposure to biomaterials. Then, we discuss recent advances in immunomodulatory strategies where hydrogels play a key role through a) physical properties including dimensionality, stiffness, porosity, and topography; b) chemical properties including wettability, electric property, and molecular presentation; and c) the delivery of bioactive molecules via chemical or physical cues. Thus, this review aims to build a conceptual and practical toolkit for the design of immune-instructive hydrogels capable of modulating the host immune response.
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15

Lee, Jong Soo, Elijah Paintsil, Vivek Gopalakrishnan, and Musie Ghebremichael. "A comparison of machine learning techniques for classification of HIV patients with antiretroviral therapy-induced mitochondrial toxicity from those without mitochondrial toxicity." BMC Medical Research Methodology 19, no. 1 (November 27, 2019). http://dx.doi.org/10.1186/s12874-019-0848-z.

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Abstract Background Antiretroviral therapy (ART) has significantly reduced HIV-related morbidity and mortality. However, therapeutic benefit of ART is often limited by delayed drug-associated toxicity. Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of ART regimens. NRTIs compete with endogenous deoxyribonucleotide triphosphates (dNTPs) in incorporation into elongating DNA chain resulting in their cytotoxic or antiviral effect. Thus, the efficacy of NRTIs could be affected by direct competition with endogenous dNTPs and/or feedback inhibition of their metabolic enzymes. In this paper, we assessed whether the levels of ribonucleotides (RN) and dNTP pool sizes can be used as biomarkers in distinguishing between HIV-infected patients with ART-induced mitochondrial toxicity and HIV-infected patients without toxicity. Methods We used data collected through a case-control study from 50 subjects. Cases were defined as HIV-infected individuals with clinical and/or laboratory evidence of mitochondrial toxicity. Each case was age, gender, and race matched with an HIV-positive without evidence of toxicity. We used a range of machine learning procedures to distinguish between patients with and without toxicity. Using resampling methods like Monte Carlo k-fold cross validation, we compared the accuracy of several machine learning algorithms applied to our data. We used the algorithm with highest classification accuracy rate in evaluating the diagnostic performance of 12 RN and 14 dNTP pool sizes as biomarkers of mitochondrial toxicity. Results We used eight classification algorithms to assess the diagnostic performance of RN and dNTP pool sizes distinguishing HIV patients with and without NRTI-associated mitochondrial toxicity. The algorithms resulted in cross-validated classification rates of 0.65–0.76 for dNTP and 0.72–0.83 for RN, following reduction of the dimensionality of the input data. The reduction of input variables improved the classification performance of the algorithms, with the most pronounced improvement for RN. Complex tree-based methods worked the best for both the deoxyribose dataset (Random Forest) and the ribose dataset (Classification Tree and AdaBoost), but it is worth noting that simple methods such as Linear Discriminant Analysis and Logistic Regression were very competitive in terms of classification performance. Conclusions Our finding of changes in RN and dNTP pools in participants with mitochondrial toxicity validates the importance of dNTP pools in mitochondrial function. Hence, levels of RN and dNTP pools can be used as biomarkers of ART-induced mitochondrial toxicity.
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