BACKGROUND: Profiling the somatic mutations of genes which may inform about tumor evolution, prognostics and treatment is becoming a standard tool in clinical oncology. Commercially available cancer gene panels rely on manually gathered cancer-related genes, in a "one-size-fits-many" solution. The design of new panels requires laborious search of literature and cancer genomics resources, with their performance on cohorts of patients difficult to estimate. RESULTS: We present OncoPaD, to our knowledge the first tool aimed at the rational design of cancer gene panels. OncoPaD estimates the cost-effectiveness of the designed panel on a cohort of tumors and provides reports on the importance of individual mutations for tumorigenesis or therapy. With a friendly interface and intuitive input, OncoPaD suggests researchers relevant sets of genes to be included in the panel, because prior knowledge or analyses indicate that their mutations either drive tumorigenesis or function as biomarkers of drug response. OncoPaD also provides reports on the importance of individual mutations for tumorigenesis or therapy that support the interpretation of the results obtained with the designed panel. We demonstrate in silico that OncoPaD designed panels are more cost-effective-i.e. detect a maximum fraction of tumors in the cohort by sequencing a minimum quantity of DNA-than available panels. CONCLUSIONS: With its unique features, OncoPaD will help clinicians and researchers design tailored next-generating sequencing (NGS) panels to detect circulating tumor DNA or biopsy specimens, thereby facilitating early and accurate detection of tumors, genomics informed therapeutic decisions, patient follow-up and timely identification of resistance mechanisms to targeted agents. OncoPaD may be accessed through http://www.intogen.org/oncopad.

A.G.-P. is supported by a Ramón y Cajal contract (RYC-2013-14554), which also funds the publication of this article. We also acknowledge funding from the Spanish Ministry of Economy and Competitiveness (grant no. SAF2012-36199), the Marató de TV3 Foundation, and the Spanish National Institute of Bioinformatics (INB). C.R.-P. is supported by an FPI fellowship. D.T. is supported by the People Programme (Marie Curie Actions) of the Seventh Framework Programme of the European Union (FP7/2007- 2013) under REA grant agreement no. 600388 and by the Agency of Competitiveness for Companies of the Government of Catalonia, ACCIÓ.