RESUMO
Anticipating and understanding cancers' need for specific gene activities is key for novel therapeutic development. Here we utilized DepMap, a cancer gene dependency screen, to demonstrate that machine learning combined with network biology can produce robust algorithms that both predict what genes a cancer is dependent on and what network features coordinate such gene dependencies. Using network topology and biological annotations, we constructed four groups of novel engineered machine learning features that produced high accuracies when predicting binary gene dependencies. We found that in all examined cancer types, F1 scores were greater than 0.90, and model accuracy remained robust under multiple hyperparameter tests. We then deconstructed these models to identify tumor type-specific coordinators of gene dependency and identified that in certain cancers, such as thyroid and kidney, tumors' dependencies are highly predicted by gene connectivity. In contrast, other histologies relied on pathway-based features such as lung, where gene dependencies were highly predictive by associations with cell death pathway genes. In sum, we show that biologically informed network features can be a valuable and robust addition to predictive pharmacology models while simultaneously providing mechanistic insights.
RESUMO
Epidemiological studies suggest that men exhibit a higher mortality rate to COVID-19 than women, yet the underlying biology is largely unknown. Here, we seek to delineate sex differences in the gene expression of viral entry proteins ACE2 and TMPRSS2, and host transcriptional responses to SARS-CoV-2 through large-scale analysis of genomic and clinical data. We first compiled 220,000 human gene expression profiles from three databases and completed the meta-information through machine learning and manual annotation. Large scale analysis of these profiles indicated that male samples show higher expression levels of ACE2 and TMPRSS2 than female samples, especially in the older group (>60 years) and in the kidney. Subsequent analysis of 6,031 COVID-19 patients at Mount Sinai Health System revealed that men have significantly higher creatinine levels, an indicator of impaired kidney function. Further analysis of 782 COVID-19 patient gene expression profiles taken from upper airway and blood suggested men and women present distinct expression changes. Computational deconvolution analysis of these profiles revealed male COVID-19 patients have enriched kidney-specific mesangial cells in blood compared to healthy patients. Together, this study suggests biological differences in the kidney between sexes may contribute to sex disparity in COVID-19.
RESUMO
Sleep apnoea is a very common sleep disorder which can cause symptoms such as daytime sleepiness, irritability and poor concentration. To monitor patients with this sleeping disorder we measured the electrical activity of the heart. The resulting electrocardiography (ECG) signals are both non-stationary and nonlinear. Therefore, we used nonlinear parameters such as approximate entropy, fractal dimension, correlation dimension, largest Lyapunov exponent and Hurst exponent to extract physiological information. This information was used to train an artificial neural network (ANN) classifier to categorize ECG signal segments into one of the following groups: apnoea, hypopnoea and normal breathing. ANN classification tests produced an average classification accuracy of 90%; specificity and sensitivity were 100% and 95%, respectively. We have also proposed unique recurrence plots for the normal, hypopnea and apnea classes. Detecting sleep apnea with this level of accuracy can potentially reduce the need of polysomnography (PSG). This brings advantages to patients, because the proposed system is less cumbersome when compared to PSG.