Prognostic subgroups of chronic pain patients using latent variable mixture modeling within a supervised machine learning framework.

The present study combined a supervised machine learning framework with an unsupervised method, finite mixture modeling, to identify prognostically meaningful subgroups of diverse chronic pain patients undergoing interdisciplinary treatment. Questionnaire data collected at pre-treatment and 1-year follow up from 11,995 patients from the Swedish Quality Registry for Pain Rehabilitation were used. Indicators measuring pain characteristics, psychological aspects, and social functioning and general health status were used to form subgroups, and pain interference at follow-up was used for the selection and the performance evaluation of models. A nested cross-validation procedure was used for determining the number of classes (inner cross-validation) and the prediction accuracy of the selected model among unseen cases (outer cross-validation). A four-class solution was identified as the optimal model. Identified subgroups were separable on indicators, predictive of long-term outcomes, and related to background characteristics. Results are discussed in relation to previous clustering attempts of patients with diverse chronic pain conditions. Our analytical approach, as the first to combine mixture modeling with supervised, targeted learning, provides a promising framework that can be further extended and optimized for improving accurate prognosis in pain treatment and identifying clinically meaningful subgroups among chronic pain patients.

Predicting sepsis using a combination of clinical information and molecular immune markers sampled in the ambulance.

Sepsis is a time dependent condition. Screening tools based on clinical parameters have been shown to increase the identification of sepsis. The aim of current study was to evaluate the additional predictive value of immunological molecular markers to our previously developed prehospital screening tools. This is a prospective cohort study of 551 adult patients with suspected infection in the ambulance setting of Stockholm, Sweden between 2017 and 2018. Initially, 74 molecules and 15 genes related to inflammation were evaluated in a screening cohort of 46 patients with outcome sepsis and 50 patients with outcome infection no sepsis. Next, 12 selected molecules, as potentially synergistic predictors, were evaluated in combination with our previously developed screening tools based on clinical parameters in a prediction cohort (n = 455). Seven different algorithms with nested cross-validation were used in the machine learning of the prediction models. Model performances were compared using posterior distributions of average area under the receiver operating characteristic (ROC) curve (AUC) and difference in AUCs. Model variable importance was assessed by permutation of variable values, scoring loss of classification as metric and with model-specific weights when applicable. When comparing the screening tools with and without added molecular variables, and their interactions, the molecules per se did not increase the predictive values. Prediction models based on the molecular variables alone showed a performance in terms of AUCs between 0.65 and 0.70. Among the molecular variables, IL-1Ra, IL-17A, CCL19, CX3CL1 and TNF were significantly higher in septic patients compared to the infection non-sepsis group. Combing immunological molecular markers with clinical parameters did not increase the predictive values of the screening tools, most likely due to the high multicollinearity of temperature and some of the markers. A group of sepsis patients was consistently miss-classified in our prediction models, due to milder symptoms as well as lower expression levels of the investigated immune mediators. This indicates a need of stratifying septic patients with a priori knowledge of certain clinical and molecular parameters in order to improve prediction for early sepsis diagnosis.Trial registration: NCT03249597. Registered 15 August 2017.

CelltrackR: An R package for fast and flexible analysis of immune cell migration data.

Visualization of cell migration via time-lapse microscopy has greatly advanced our understanding of the immune system. However, subtle differences in migration dynamics are easily obscured by biases and imaging artifacts. While several analysis methods have been suggested to address these issues, an integrated tool implementing them is currently lacking. Here, we present celltrackR, an R package containing a diverse set of state-of-the-art analysis methods for (immune) cell tracks. CelltrackR supports the complete pipeline for track analysis by providing methods for data management, quality control, extracting and visualizing migration statistics, clustering tracks, and simulating cell migration. CelltrackR supports the analysis of both 2D and 3D cell tracks. CelltrackR is an open-source package released under the GPL-2 license, and is freely available on both GitHub and CRAN. Although the package was designed specifically for immune cell migration data, many of its methods will also be of use in other research areas dealing with moving objects.