Tumors are typically sequenced to depths of 75x–100x (exome) or 30x–50x (whole genome).

Authors in the journal Cell Systems demonstrate that current sequencing paradigms are inadequate for tumors that are impure, aneuploid, or clonally heterogeneous.

To reassess optimal sequencing strategies, they performed ultra-deep (up to ∼312x) whole genome sequencing and exome capture (up to ∼433x) of a primary acute myeloid leukemia, its subsequent relapse, and a matched normal skin sample.

Authors tested multiple alignment and variant calling algorithms and validated ∼200,000 putative SNVs by sequencing them to depths of ∼1,000x. Additional targeted sequencing provided over 10,000x coverage and ddPCR assays provided up to ∼250,000x sampling of selected sites.

They 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: phs000159).

http://www.cell.com/cell-systems/abstract/S2405-4712(15)00113-1