Predictive modeling of antibiotic eradication therapy success for new-onset Pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis.
Lucía Graña-MiragliaNadia Morales-LizcanoPauline W WangDavid M HwangYvonne C W YauValerie J WatersDavid S GuttmanPublished in: PLoS computational biology (2023)
Chronic Pseudomonas aeruginosa (Pa) lung infections are the leading cause of mortality among cystic fibrosis (CF) patients; therefore, the eradication of new-onset Pa lung infections is an important therapeutic goal that can have long-term health benefits. The use of early antibiotic eradication therapy (AET) has been shown to clear the majority of new-onset Pa infections, and it is hoped that identifying the underlying basis for AET failure will further improve treatment outcomes. Here we generated machine learning models to predict AET outcomes based on pathogen genomic data. We used a nested cross validation design, population structure control, and recursive feature selection to improve model performance and showed that incorporating population structure control was crucial for improving model interpretation and generalizability. Our best model, controlling for population structure and using only 30 recursively selected features, had an area under the curve of 0.87 for a holdout test dataset. The top-ranked features were generally associated with motility, adhesion, and biofilm formation.
Keyphrases
- pseudomonas aeruginosa
- biofilm formation
- cystic fibrosis
- candida albicans
- machine learning
- staphylococcus aureus
- helicobacter pylori infection
- acinetobacter baumannii
- escherichia coli
- lung function
- healthcare
- public health
- ejection fraction
- pulmonary hypertension
- big data
- cardiovascular events
- type diabetes
- deep learning
- mental health
- young adults
- electronic health record
- artificial intelligence
- mesenchymal stem cells
- helicobacter pylori
- insulin resistance
- chronic obstructive pulmonary disease
- adipose tissue
- weight loss
- social media
- drug induced
- coronary artery disease
- gene expression
- patient reported outcomes
- climate change
- copy number
- genome wide