HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Oncogene Manuscript Author . Author manuscript; Manuscript Author available in PMC 2018 July 11. Published in final edited form as: Oncogene. 2018 January 11; 37(2): 185–196. doi:10.1038/onc.2017.322. A system for detecting high impact-low frequency mutations in primary tumors and metastases Manjushree Anjanappa1,¶, Yangyang Hao2,¶, Edward R Simpson Jr.2, Poornima Bhat- Nakshatri1, Jennifer B Nelson3, Sarah A Tersey3, Raghavendra G Mirmira3, Aaron A Cohen- Gadol5, M. Reza Saadatzadeh3, Lang Li2,4, Fang Fang6, Kenneth P. Nephew6, Kathy D. Miller7, Yunlong Liu2,4,*, and Harikrishna Nakshatri1,8,9,* 1Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA 2Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, IN 46202, USA 3Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA 4Department of Medical and Molecular Genetics, Indiana University School of Medicine, IN 46202, USA 5Department of Neurosurgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA 6Medical Science Program, Indiana University, Bloomington, IN 47401, USA 7Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA 8Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA 9Roudebush VA Medical Center, Indianapolis, IN 46202, USA Abstract Tumor complexity and intratumor heterogeneity contribute to subclonal diversity. Despite advances in next-generation sequencing (NGS) and bioinformatics, detecting rare mutations in primary tumors and metastases contributing to subclonal diversity is a challenge for precision genomics. Here, in order to identify rare mutations, we adapted a recently described epithelial *Co-corresponding Authors (
[email protected] and
[email protected]).