Library preparation and sequencing of cell lines and Sample A with WES1 (Roche) and WES2 (IDT) exome kits performed at University of Texas Southwestern Medical Center and Novogene

All genomic DNA samples were provided by Agilent (Agilent Technologies). Whole exome sequencing libraries were constructed using KAPA Hyper Prep kit (Kapa Biosystems) and Roche NimbleGen SeqCap EZ hybridization and wash kit (Roche Sequencing Solutions), or Next Ultra II DNA Library Prep kit for Illumina (New England Biolabs) and IDT xGen hybridization and wash kit (Integrated DNA technologies, Inc.) according to the manufacturers’ instructions. Briefly, genomic DNA was sheared to an average fragment size of 200 bp or 300 bp on Covaris S220 (Covaris). Ten nanograms, for 10 UHR cell lines and Sample B in duplicate, or 100 ng for Sample A in triplicate, of fragmented DNA, was used as input for the library preparation. Samples were sequentially end-repaired, A-tailed, and adapter-ligated. The libraries were then subjected to minimal PCR cycling and quantified with Agilent DNA 1000 assay. One microgram of each sample library was hybridized with WES1 and 500 ng of each sample library with WES2. The hybridized probe-target complexes were captured with streptavidin beads and washed to remove non-targeted DNA. Captured libraries were amplified by PCR, and the quality of the libraries was validated by Agilent high sensitivity DNA assay and quantitative PCR. The libraries from each panel were pooled in equimolar amounts and subjected to 150-bppaired-end sequencing (PE150) at Novogene on an Illumina HiSeq 4000 for the cell line libraries and on an Illumina HiSeq X Ten for Sample A libraries.