FastClone is a probabilistic tool for deconvoluting tumor heterogeneity in bulk-sequencing samples

Dissecting tumor heterogeneity is a key to understanding the complex mechanisms underlying drug resistance in cancers. The rich literature of pioneering studies on tumor heterogeneity analysis spurred a recent community-wide benchmark study that compares diverse modeling algorithms. Here we present FastClone, a top-performing algorithm in accuracy in this benchmark. FastClone improves over existing methods by allowing the deconvolution of subclones that have independent copy number variation events within the same chromosome regions. We characterize the behavior of FastClone in identifying subclones using stage III colon cancer primary tumor samples as well as simulated data. It achieves approximately 100-fold acceleration in computation for both simulated and patient data. The efficacy of FastClone will allow its application to large-scale data and clinical data, and facilitate personalized medicine in cancers. Multiple algorithms exist for predicting heterogeneity and clonal architecture from the bulk sequencing of tumor tissue. Here, the authors report on an algorithm, FastClone, which was developed from a DREAM challenge and show that FastClone can accurately predict clonality in simulated data and data from colon cancer.