This study demonstrates the feasibility of a large-scale compendium of functional perturbations coupled to an information-rich gene expression read-out. By making L1000 expression profiling inexpensive, scale up became tractable. The L1000 platform has certain attributes and limitations worth considering. Because L1000 is hybridization-based, it is possible to monitor the expression of non-abundant transcripts. While such rare transcripts (e.g., encoding transcription factors) can also be detected by RNA-seq, high depth of sequence coverage is needed, and this can become cost-prohibitive. Nevertheless, as sequencing costs drop, RNA-sequencing-based approaches such as Perturb-Seq (Dixit et al., 2016) should be considered.
