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Jiang","year":"2016","journal-title":"Proceedings of the National Academy of Sciences USA"},{"issue":"1","key":"ref36","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13059-015-0592-6","article-title":"BitPhylogeny: A Probabilistic Framework for Reconstructing Intra-Tumor Phylogenies","volume":"16","author":"K Yuan","year":"2015","journal-title":"Genome Biology"},{"issue":"4","key":"ref37","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nmeth.2883","article-title":"PyClone: Statistical Inference of Clonal Population Structure in Cancer","volume":"11","author":"A Roth","year":"2014","journal-title":"Nature Methods"},{"issue":"12","key":"ref38","doi-asserted-by":"crossref","first-page":"i106","DOI":"10.1093\/bioinformatics\/btq213","article-title":"Robust Unmixing of Tumor States in Array Comparative Genomic Hybridization Data","volume":"26","author":"D Tolliver","year":"2010","journal-title":"Bioinformatics"},{"issue":"10","key":"ref39","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ng.2764","article-title":"The Cancer Genome Atlas Pan-Cancer Analysis Project","volume":"45","author":"JN Weinstein","year":"2013","journal-title":"Nature Genetics"},{"issue":"11","key":"ref40","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1080\/14786440109462720","article-title":"LIII. On Lines and Planes of Closest Fit to Systems of Points in Space","volume":"2","author":"K Pearson","year":"1901","journal-title":"The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Cheng SW, Chiu MK. Dimension Detection via Slivers. In: Proceedings of the Twentieth Annual ACM-SIAM Symposium on Discrete Algorithms: 1001\u20131010 January 2009; New York. ACM-SIAM; 2009. p. 1001\u20131010.","DOI":"10.1137\/1.9781611973068.109"},{"issue":"1","key":"ref42","first-page":"97","article-title":"Medoidshift Clustering Applied to Genomic Bulk Tumor Data","volume":"17","author":"T Roman","year":"2016","journal-title":"BMC Genomics"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Sheikh YA, Khan EA, Kanade T. Mode-seeking by Medoidshifts. In: Computer Vision, 2007. ICCV 2007. IEEE 11th International Conference on. 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