Deep Learning Implicitly Handles Tissue Specific Phenomena to Predict Tumor DNA Accessibility and Immune Activity

DNA accessibility is a key dynamic feature of chromatin regulation that can potentiate transcriptional events and tumor progression. To gain insight into chromatin state across existing tumor data, we improved neural network models for predicting accessibility from DNA sequence and extended them to incorporate a global set of RNA sequencing gene expression inputs. Our expression-informed model expanded the application domain beyond specific tissue types to tissues not present in training and achieved consistently high accuracy in predicting DNA accessibility at promoter and promoter flank regions. We then leveraged our new tool by analyzing the DNA accessibility landscape of promoters across The Cancer Genome Atlas. We show that in lung adenocarcinoma the accessibility perspective uniquely highlights immune pathways inversely correlated with a more open chromatin state and that accessibility patterns learned from even a single tumor type can discriminate immune inflammation across many cancers, often with direct relation to patient prognosis. [Display omitted] •Tissue-specific aspects of DNA can be predicted in new tissue types if given RNA-seq•DNA accessibility prediction is most reliable at promoter and promoter flank regions•Clustering global chromatin state highlights immune pathway activity in tumors•Accessibility patterns discriminate immune active tumors that can differ in prognosis Bioinformatics; Neural Networks; Cancer