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Background  Genetic information is becoming more readily available and is increasingly being used to predict patient cancer types as well as their subtypes. Most classification methods thus far utilize somatic mutations as independent features for classification and are limited by study power. We aim to develop a novel method to effectively explore the landscape of genetic variants, including germline variants, and small insertions and deletions for cancer type prediction.Results  We proposed DeepCues, a deep learning model that utilizes convolutional neural networks to unbiasedly derive features from raw cancer DNA sequencing data for disease classification and relevant gene discovery. Using raw whole-exome sequencing as features, germline variants and somatic mutations, including insertions and deletions, were interactively amalgamated for feature generation and cancer prediction. We applied DeepCues to a dataset from TCGA to classify seven different types of major cancers and obtained an overall accuracy of 77.6%. We compared DeepCues to conventional methods and demonstrated a significant overall improvement ( p  < 0.001). Strikingly, using DeepCues, the top 20 breast cancer relevant genes we have identified, had a 40% overlap with the top 20 known breast cancer driver genes.    Conclusion  Our results support DeepCues as a novel method to improve the representational resolution of DNA sequencings and its power in deriving features from raw sequences for cancer type prediction, as well as discovering new cancer relevant genes.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12859-021-04400-4.

Deep learning for cancer type classification and driver gene identification