Genes, behavior, and next-generation sequencing: The first 10 years

The first RNA sequence or “transcriptome” from brain was published in 2008 (Mortazavi et al., 2008); they compared the data with microarray results from the same sample and found good concordance (r = 0.83). As sequencing the brain transcriptome (RNA-Seq) approaches its 10th year, it is appropriate to revisit the literature, to focus on the progress that has been made and to speculate on what the future will hold. Although the adoption of RNA-Seq in the brain-behavior context was initially slow, in 2017 alone, we expect to see >200 publications. Of course, there are thousands more RNA-Seq publications, e.g., in cancer research, that have helped refine the technique, provided new analysis tools, and have helped set the parameters for experimental design. However, the brain is unique, given that for a particular behavior or condition, multiple brain regions and cell types are likely to be involved. Additionally, the brain transcriptome is highly enriched in alternative transcripts and noncoding RNAs that require deep sequencing for adequate analyses. Although our emphasis here is on four species (mouse, rat, macaque, and human), RNA-Seq is also being implemented in a wide range of species, e.g., flies, worms, fish, and bees, each of which may require a special sequencing perspective.