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      Machine-learning algorithms define pathogen-specific local immune fingerprints in peritoneal dialysis patients with bacterial infections

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          Abstract

          The immune system has evolved to sense invading pathogens, control infection, and restore tissue integrity. Despite symptomatic variability in patients, unequivocal evidence that an individual's immune system distinguishes between different organisms and mounts an appropriate response is lacking. We here used a systematic approach to characterize responses to microbiologically well-defined infection in a total of 83 peritoneal dialysis patients on the day of presentation with acute peritonitis. A broad range of cellular and soluble parameters was determined in peritoneal effluents, covering the majority of local immune cells, inflammatory and regulatory cytokines and chemokines as well as tissue damage–related factors. Our analyses, utilizing machine-learning algorithms, demonstrate that different groups of bacteria induce qualitatively distinct local immune fingerprints, with specific biomarker signatures associated with Gram-negative and Gram-positive organisms, and with culture-negative episodes of unclear etiology. Even more, within the Gram-positive group, unique immune biomarker combinations identified streptococcal and non-streptococcal species including coagulase-negative Staphylococcus spp. These findings have diagnostic and prognostic implications by informing patient management and treatment choice at the point of care. Thus, our data establish the power of non-linear mathematical models to analyze complex biomedical datasets and highlight key pathways involved in pathogen-specific immune responses.

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          Most cited references 27

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          The danger model: a renewed sense of self.

          For over 50 years immunologists have based their thoughts, experiments, and clinical treatments on the idea that the immune system functions by making a distinction between self and nonself. Although this paradigm has often served us well, years of detailed examination have revealed a number of inherent problems. This Viewpoint outlines a model of immunity based on the idea that the immune system is more concerned with entities that do damage than with those that are foreign.
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            Gene selection and classification of microarray data using random forest

            Background Selection of relevant genes for sample classification is a common task in most gene expression studies, where researchers try to identify the smallest possible set of genes that can still achieve good predictive performance (for instance, for future use with diagnostic purposes in clinical practice). Many gene selection approaches use univariate (gene-by-gene) rankings of gene relevance and arbitrary thresholds to select the number of genes, can only be applied to two-class problems, and use gene selection ranking criteria unrelated to the classification algorithm. In contrast, random forest is a classification algorithm well suited for microarray data: it shows excellent performance even when most predictive variables are noise, can be used when the number of variables is much larger than the number of observations and in problems involving more than two classes, and returns measures of variable importance. Thus, it is important to understand the performance of random forest with microarray data and its possible use for gene selection. Results We investigate the use of random forest for classification of microarray data (including multi-class problems) and propose a new method of gene selection in classification problems based on random forest. Using simulated and nine microarray data sets we show that random forest has comparable performance to other classification methods, including DLDA, KNN, and SVM, and that the new gene selection procedure yields very small sets of genes (often smaller than alternative methods) while preserving predictive accuracy. Conclusion Because of its performance and features, random forest and gene selection using random forest should probably become part of the "standard tool-box" of methods for class prediction and gene selection with microarray data.
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              Using Support Vector Machine to identify imaging biomarkers of neurological and psychiatric disease: a critical review.

              Standard univariate analysis of neuroimaging data has revealed a host of neuroanatomical and functional differences between healthy individuals and patients suffering a wide range of neurological and psychiatric disorders. Significant only at group level however these findings have had limited clinical translation, and recent attention has turned toward alternative forms of analysis, including Support-Vector-Machine (SVM). A type of machine learning, SVM allows categorisation of an individual's previously unseen data into a predefined group using a classification algorithm, developed on a training data set. In recent years, SVM has been successfully applied in the context of disease diagnosis, transition prediction and treatment prognosis, using both structural and functional neuroimaging data. Here we provide a brief overview of the method and review those studies that applied it to the investigation of Alzheimer's disease, schizophrenia, major depression, bipolar disorder, presymptomatic Huntington's disease, Parkinson's disease and autistic spectrum disorder. We conclude by discussing the main theoretical and practical challenges associated with the implementation of this method into the clinic and possible future directions. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Kidney Int
                Kidney Int
                Kidney International
                Elsevier
                0085-2538
                1523-1755
                1 July 2017
                July 2017
                : 92
                : 1
                : 179-191
                Affiliations
                [1 ]Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
                [2 ]Mologic Ltd., Bedford Technology Park, Thurleigh, Bedford, UK
                [3 ]Directorate of Critical Care, Cardiff and Vale University Health Board, University Hospital of Wales, Heath Park, Cardiff, UK
                [4 ]Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan City, Taiwan
                [5 ]Wales Kidney Research Unit, Heath Park Campus, Cardiff, UK
                [6 ]Directorate of Nephrology and Transplantation, Cardiff and Vale University Health Board, University Hospital of Wales, Heath Park, Cardiff, UK
                [7 ]Cardiff Business School, Cardiff University, Cardiff, UK
                [8 ]Systems Immunity Research Institute, Cardiff University, Cardiff, UK
                Author notes
                [] Correspondence: Matthias Eberl, Division of Infection and Immunity, Henry Wellcome Building, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.Division of Infection and ImmunityHenry Wellcome Building, School of MedicineCardiff University, Heath ParkCardiff CF14 4XNUK eberlm@ 123456cf.ac.uk
                [9]

                Present address: School of Environment and Life Sciences, University of Salford, Salford M5 4WT, UK.

                Article
                S0085-2538(17)30068-6
                10.1016/j.kint.2017.01.017
                5484022
                28318629
                © 2017 International Society of Nephrology.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                Categories
                Clinical Investigation

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