A number of approaches have been developed to call somatic variation in high-throughput sequencing data. Here, we present an adaptive approach to calling somatic variations. Our approach trains a deep feed-forward neural network with semi-simulated data. Semi-simulated datasets are constructed by planting somatic mutations in real datasets where no mutations are expected. Using semi-simulated data makes it possible to train the models with millions of training examples, a usual requirement for successfully training deep learning models. We initially focus on calling variations in RNA-Seq data. We derive semi-simulated datasets from real RNA-Seq data, which offer a good representation of the data the models will be applied to. We test the models on independent semi-simulated data as well as pure simulations. On independent semi-simulated data, models achieve an AUC of 0.973. When tested on semi-simulated exome DNA datasets, we find that the models trained on RNA-Seq data remain predictive (sens ~0.4 & spec ~0.9 at cutoff of P>=0.9), albeit with lower overall performance (AUC=0.737). Interestingly, while the models generalize across assay, training on RNA-Seq data lowers the confidence for a group of mutations. Haloplex exome specific training was also performed, demonstrating that the approach can produce probabilistic models tuned for specific assays and protocols. We found that the method adapts to the characteristics of experimental protocol. We further illustrate these points by training a model for a trio somatic experimental design when germline DNA of both parents is available in addition to data about the individual. These models are distributed with Goby (http://goby.campagnelab.org).