TY - JOUR T1 - High throughput gene expression profiling of yeast colonies with microgel-culture Drop-seq JF - bioRxiv DO - 10.1101/416966 SP - 416966 AU - Leqian Liu AU - Chiraj Dalal AU - Ben Heineike AU - Adam Abate Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/09/15/416966.abstract N2 - Yeasts can be engineered into “living foundries” for non-natural chemical production by reprogramming their genome using a synthetic biology “design-build-test” cycle. While methods for “design” and “build” are scalable and efficient, “test” remains a labor-intensive bottleneck, limiting the effectiveness of the genetic reprogramming results. Here we describe Isogenic Colony Sequencing (ICO-seq), a massively-parallel strategy to assess the gene expression, and thus engineered pathway efficacy, of large numbers of genetically distinct yeast colonies. We use the approach to characterize opaque-white switching in 658 C. albicans colonies. By profiling transcriptomes of 1642 engineered S. cerevisiae strains, we use it to assess gene expression heterogeneity in a protein mutagenesis library. Our approach will accelerate synthetic biology by allowing facile and cost-effective transcriptional profiling of large numbers of genetically distinct yeast strains. ER -