Corrigendum: Identifying predictors of clinical outcomes using the projection-predictive feature selection-a proof of concept on the example of Crohn's disease.

[This corrects the article DOI: 10.3389/fped.2023.1170563.].

Evidence for microtubule nucleation at the Golgi in breast cancer cells.

Golgi-derived microtubule (MT) arrays are essential to directionally persistent cell migration and vesicle transport. In this study, we have examined MT nucleation sites in two breast cancer cell lines, MDA-MB-231 and MCF-7, with the hypothesis that only the migratory invasive MDA-MB-231 cells exhibit MTs originating from the Golgi. MTs were disassembled and allowed to slightly regrow so individual nucleation sites could then be observed via fluorescently tagged antibodies (α-tubulin, cis-Golgi marker GM130, and EB1-a MT plus-end binding protein) and confocal microscopy. To determine if MT nucleation at the Golgi is more apparent during active migration compared to when cells are stationary, cells were treated with the chemoattractant epidermal growth factor (EGF) and examined for colocalizations between the Golgi, α-tubulin, and γ-tubulin. Images were analyzed qualitatively for color overlap, and quantitatively using Manders Colocalization Coefficients. Differences between groups were tested for significance using one-way analysis of variances and Tukey's post hoc test. Significantly higher colocalization values (coloc) in the highly invasive MDA-MB-231 cells (α-tubulin coloc GM130 = 0.39, GM130 coloc α-tubulin = 0.82, GM130 coloc EB1 = 0.24, and EB1 coloc GM130 = 0.38) compared to the weakly invasive MCF-7 cells (0.15, 0.08, 0.02, and 0.16, respectively) were observed. EGF-treated cells exhibited higher colocalization values than control cells for three of the four protein combinations tested, but EGF-treated MDA-MB-231 cells exhibited significantly higher values (α-tubulin coloc GM130 = 0.20, GM130 coloc α-tubulin = 0.89, and γ-tubulin coloc GM130 = 0.47) than both control groups as well as the EGF-treated MCF-7 cells. Results support the hypothesis that MT nucleation at the Golgi occurs more frequently in the invasive MDA-MB-231 cell line compared to the weakly invasive MCF-7 cells. The presence or absence of Golgi-derived MTs may help to explain the difference in migratory potential commonly exhibited by these two cell lines.

Identifying predictors of clinical outcomes using the projection-predictive feature selection-a proof of concept on the example of Crohn's disease.

Objectives: Several clinical disease activity indices (DAIs) have been developed to noninvasively assess mucosal healing in pediatric Crohn's disease (CD). However, their clinical application can be complex. Therefore, we present a new way to identify the most informative biomarkers for mucosal inflammation from current markers in use and, based on this, how to obtain an easy-to-use DAI for clinical practice. A further aim of our proof-of-concept study is to demonstrate how the performance of such a new DAI can be compared to that of existing DAIs. Methods: The data of two independent study cohorts, with 167 visits from 109 children and adolescents with CD, were evaluated retrospectively. A variable selection based on a Bayesian ordinal regression model was applied to select clinical or standard laboratory parameters as predictors, using an endoscopic outcome. The predictive performance of the resulting model was compared to that of existing pediatric DAIs. Results: With our proof-of-concept dataset, the resulting model included C-reactive protein (CRP) and fecal calprotectin (FC) as predictors. In general, our model performed better than the existing DAIs. To show how our Bayesian approach can be applied in practice, we developed a web application for predicting disease activity for a new CD patient or visit. Conclusions: Our work serves as a proof-of-concept, showing that the statistical methods used here can identify biomarkers relevant for the prediction of a clinical outcome. In our case, a small number of biomarkers is sufficient, which, together with the web interface, facilitates the clinical application. However, the retrospective nature of our study, the rather small amount of data, and the lack of an external validation cohort do not allow us to consider our results as the establishment of a novel DAI for pediatric CD. This needs to be done with the help of a prospective study with more data and an external validation cohort in the future.