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10.1016/j.cels.2015.08.015

http://scihub22266oqcxt.onion/10.1016/j.cels.2015.08.015
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suck abstract from ncbi


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      Cell+Syst 2015 ; 1 (3 ): 210-223
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  • Optimizing cancer genome sequencing and analysis #MMPMID26645048
  • Griffith M ; Miller CA ; Griffith OL ; Krysiak K ; Skidmore ZL ; Ramu A ; Walker JR ; Dang HX ; Trani L ; Larson DE ; Demeter RT ; Wendl MC ; McMichael JF ; Austin RE ; Magrini V ; McGrath SD ; Ly A ; Kulkarni S ; Cordes MG ; Fronick CC ; Fulton RS ; Maher CA ; Ding L ; Klco JM ; Mardis ER ; Ley TJ ; Wilson RK
  • Cell Syst 2015[Sep]; 1 (3 ): 210-223 PMID26645048 show ga
  • Tumors are typically sequenced to depths of 75-100× (exome) or 30-50× (whole genome). We demonstrate that current sequencing paradigms are inadequate for tumors that are impure, aneuploid or clonally heterogeneous. To reassess optimal sequencing strategies, we performed ultra-deep (up to ~312×) whole genome sequencing (WGS) and exome capture (up to ~433×) of a primary acute myeloid leukemia, its subsequent relapse, and a matched normal skin sample. We tested multiple alignment and variant calling algorithms and validated ~200,000 putative SNVs by sequencing them to depths of ~1,000×. Additional targeted sequencing provided over 10,000× coverage and ddPCR assays provided up to ~250,000× sampling of selected sites. We evaluated the effects of different library generation approaches, depth of sequencing, and analysis strategies on the ability to effectively characterize a complex tumor. This dataset, representing the most comprehensively sequenced tumor described to date, will serve as an invaluable community resource (dbGaP accession id phs000159).
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