학술논문

DAGBagM: learning directed acyclic graphs of mixed variables with an application to identify protein biomarkers for treatment response in ovarian cancer
Document Type
article
Source
BMC Bioinformatics, Vol 23, Iss 1, Pp 1-19 (2022)
Subject
Proteomics
Sensitive and resistant/refractory
Hill climbing
Bootstrap aggregation
Computer applications to medicine. Medical informatics
R858-859.7
Biology (General)
QH301-705.5
Language
English
ISSN
1471-2105
Abstract
Abstract Background Applying directed acyclic graph (DAG) models to proteogenomic data has been shown effective for detecting causal biomarkers of complex diseases. However, there remain unsolved challenges in DAG learning to jointly model binary clinical outcome variables and continuous biomarker measurements. Results In this paper, we propose a new tool, DAGBagM, to learn DAGs with both continuous and binary nodes. By using appropriate models, DAGBagM allows for either continuous or binary nodes to be parent or child nodes. It employs a bootstrap aggregating strategy to reduce false positives in edge inference. At the same time, the aggregation procedure provides a flexible framework to robustly incorporate prior information on edges. Conclusions Through extensive simulation experiments, we demonstrate that DAGBagM has superior performance compared to alternative strategies for modeling mixed types of nodes. In addition, DAGBagM is computationally more efficient than two competing methods. When applying DAGBagM to proteogenomic datasets from ovarian cancer studies, we identify potential protein biomarkers for platinum refractory/resistant response in ovarian cancer. DAGBagM is made available as a github repository at https://github.com/jie108/dagbagM .