RNA sequencing (RNA-seq) has become the standard for gene expression profiling, and thus we sought to benchmark L1000 against it. We note that while RNA-seq is attractive given its unbiased nature, it suffers from inability to detect non-abundant transcripts without deep sequencing that results in higher costs. The L1000 platform is hybridization-based, thus making the detection of non-abundant transcripts feasible. As an initial assessment of cross-platform performance, mRNA samples from 6 cell lines were profiled on L1000, Affymetrix U133A and Illumina BeadChip arrays, and by RNA-seq. Hierarchical clustering of these data grouped samples by cell type, not measurement platform (Figure 1D and 1E, upper panel).