Generating the Transcriptional Regulation View of Transcriptomic Features for Prediction Task and Dark Biomarker...

Transcriptome represents the expression levels of many genes in a sample and has been widely used in biological research and clinical practice. Researchers usually focused on transcriptomic biomarkers with differential representations between a phenotype group and a control group of samples. This study presented a multitask graph-attention network (GAT) learning framework to learn the complex inter-genic interactions of the reference samples. A demonstrative reference model was pre-trained on the healthy samples (HealthModel), which could be directly used to generate the model-based quantitative transcriptional regulation (mqTrans) view of the independent test transcriptomes. The generated mqTrans view of transcriptomes was demonstrated by prediction tasks and dark biomarker detection. The coined term "dark biomarker" stemmed from its definition that a dark biomarker showed differential representation in the mqTrans view but no differential expression in its original expression level. A dark biomarker was always overlooked in traditional biomarker detection studies due to the absence of differential expression. The source code and the manual of the pipeline HealthModelPipe can be downloaded from http://www.healthinformaticslab.org/supp/resources.php.