Workflow of comprehensive combined DNA and RNA genomic analysis in clinical specimens and coverage distribution of all exons. (A) DNA and RNA are extracted from fresh blood and bone marrow aspirate (BMA) specimens procured in EDTA or FFPE biopsy/surgical specimens; cDNA from 300 to 500 ng RNA and 50 to 200 ng DNA undergoes whole-genome shotgun library construction. cDNA libraries are hybrid capture selected for 265 genes known to be rearranged in RNA and DNA libraries are hybrid capture selected for 405 genes known to be altered in DNA. Hybrid-capture selected libraries are sequenced to high depth using the Illumina HiSeq2500 platform; sequence data are processed using a customized analysis pipeline designed to accurately detect multiple classes of genomic alterations: base substitutions, short insertions/deletions, CNAs, and gene fusions; detected mutations are annotated according to clinical significance and reported. (B) Coverage distribution in DNAseq of all genes in 108 validation samples including 4 Hapmap controls and 104 hematologic tumor specimens.