A practical guide to sequencing in neuropsychiatric research

Technology and computational analysis to profile RNA and DNA at genome-wide scale has rapidly evolved in the last two decades, with a concomitant rise in their application within neuroscience and psychiatry research. These technologies initially offered “unbiased” insights and the potential to discover previously unconsidered molecular mediators of disease and development. The more recent advent and adoption of single-cell/nucleus and spatial “omics” sequencing provides unprecedented insights into cellular processes within heterogeneous tissues. These advances are especially advantageous in neuropsychiatric research, which faces unique challenges due to the brain’s cellular heterogeneity, dynamic development, and the complex, polygenic nature of many psychiatric disorders. Still, different sequencing techniques are better suited for different questions and the most fine-grained (and expensive) approaches are not always necessary. Here, we offer a simple primer on the pros, cons, and best applications for currently available sequencing technologies.