Allelic imbalance of chromatin accessibility in cancer identifies causal risk variants and their mechanisms

A method, comprising:

• receiving sequencing data for a plurality of accessibility features;
• generating a predictive model using the sequencing data to predict germline genetic variants associated with one or more of the plurality of accessibility features that result in allelic imbalance, the predictive model trained using transcription-factor (TF) binding accessibility;
• inputting sample data into the predictive model;
• and
• outputting the predicted germline genetic variants that result in the allelic imbalance.

A method of generating a predictive model for determining genomic regions that increase cancer risk heritability, comprising:

• receiving sequencing data for a plurality of accessibility features;
• training a predictive model using transcription-factor (TF) binding accessibility to determine genetic predictors for each accessibility feature of the plurality of accessibility features;
• and
• identifying accessibility quantitative trait loci (as-aQTLs) that are associated with cancer risk for each accessibility feature based on the trained predictive model.

A system, comprising:

• one or more storage devices configured to store sequencing data for a plurality of accessibility features, and a processor coupled to the one or more storage devices, the processor configured to:
• receive the sequencing data for a plurality of accessibility features;
• generate a predictive model using the sequencing data to predict germline genetic variants associated with one or more of the plurality of accessibility features that result in allelic imbalance, the predictive model trained using transcription-factor (TF) binding accessibility;
• input sample data into the predictive model;
• and
• output the predicted germline genetic variants that result in the allelic imbalance.