Preclinical models are ubiquitous and essential for drug discovery, yet our understanding of how well they translate to clinical outcomes is limited. In this study, we investigate the translational success of treatments for Clostridium difficile infection from animal models to human patients. Our analysis shows that only 36% of the preclinical and clinical experiment pairs result in translation success. Univariate analysis shows that the sustained response endpoint is correlated with translation failure (SRC = -0.20, p-value = 1.53 × 10-54), and explainability analysis of multi-variate random forest models shows that both sustained response endpoint and subject age are negative predictors of translation success. We have developed a recommendation system to help plan the right preclinical study given factors such as drug dosage, bacterial dosage, and preclinical/clinical endpoint. With an accuracy of 0.76 (F1 score of 0.71) and by using only 7 features (out of 68 total), the proposed system boosts translational efficiency by 25%. The method presented can extend to any disease and can serve as a preclinical to clinical translation decision support system to accelerate drug discovery and de-risk clinical outcomes.

Depression is a major cause of disability and mortality for young people worldwide and is typically first diagnosed during adolescence. In this work, we present a machine learning framework to predict adolescent depression occurring between ages 12 and 18 years using environmental, biological, and lifestyle features of the child, mother, and partner from the child's prenatal period to age 10 years using data from 8467 participants enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). We trained and compared several cross-sectional and longitudinal machine learning techniques and found the resulting models predicted adolescent depression with recall (0.59 ± 0.20), specificity (0.61 ± 0.17), and accuracy (0.64 ± 0.13), using on average 39 out of the 885 total features (4.4%) included in the models. The leading informative features in our predictive models of adolescent depression were female sex, parental depression and anxiety, and exposure to stressful events or environments. This work demonstrates how using a broad array of evidence-driven predictors from early in life can inform the development of preventative decision support tools to assist in the early detection of risk for mental illness.

Interest in animal cell-based meat (ACBM) or laboratory-grown meat has been increasing; however, the economic viability of these potential products has not been thoroughly vetted. Recent studies suggest monoclonal antibody production technology can be adapted for the industrialization of ACBM production. This study provides a scenario-based assessment of the projected cost per kilogram of ACBM produced in the United States based on cellular metabolic requirements and process/chemical engineering conventions. A sensitivity analysis of the model identified the nine most influential cost factors for ACBM production out of 67 initial parameters. The results indicate that technological performance will need to approach technical limits for ACBM to achieve profitably as a commodity. However, the model also suggests that low-volume high-value specialty products could be viable based on current technology.

Introduction

Biogenic amines play important roles throughout cellular metabolism. This study explores a role of biogenic amines in glioblastoma pathogenesis. Here, we characterize the plasma levels of biogenic amines in glioblastoma patients undergoing standard-of-care treatment.

Methods

We examined 138 plasma samples from 36 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma at multiple stages of treatment. Untargeted gas chromatography-time of flight mass spectrometry (GC-TOF MS) was used to measure metabolite levels. Machine learning approaches were then used to develop a predictive tool based on these datasets.

Results

Surgery was associated with increased levels of 12 metabolites and decreased levels of 11 metabolites. Chemoradiation was associated with increased levels of three metabolites and decreased levels of three other metabolites. Ensemble learning models, specifically random forest (RF) and AdaBoost (AB), accurately classified treatment phases with high accuracy (RF: 0.81 ± 0.04, AB: 0.78 ± 0.05). The metabolites sorbitol and N-methylisoleucine were identified as important predictive features and confirmed via SHAP.

Conclusion

To our knowledge, this is the first study to describe plasma biogenic amine signatures throughout the treatment of patients with glioblastoma. A larger study is needed to confirm these results with hopes of developing a diagnostic algorithm.