Massively parallel identification of cis-regulatory variants in yeast promoters - Annotation runs

Sequence variation in regulatory DNA alters gene expression and shapes genetically complex traits. However, the identification of individual, causal regulatory variants is challenging. Here, we used a massively parallel reporter assay to measure the cis-regulatory consequences of 5,832 natural DNA variants in the promoters of 2,503 genes in the yeast Saccharomyces cerevisiae. We identified 451 causal variants, which underlie genetic loci known to affect gene expression. Several promoters harbored multiple causal variants. In five promoters, pairs of variants showed non-additive, epistatic interactions. Causal variants were enriched at conserved nucleotides, tended to have low derived allele frequency, and were depleted from promoters of essential genes, consistent with the action of negative selection. Causal variants were enriched for alterations in transcription factor binding sites. Models integrating these features provided modest, but statistically significant, ability to predict causal variants. This work revealed a complex molecular basis for cis-acting regulatory variation. This study used a massively parallel reporter assay to study cis-effects of yeast promoter variants on gene expression. This repository provides sequencing data used in barcode annotation. Specifically, the project used designed, synthetic DNA oligos, each tagged with multiple DNA barcodes of length 20 bp that were randomly assigned by PCR. The annotation runs mapped each barcode to the oligo it tagged. There were two sub-libraries ("TSS" and "Upstream"). Each sub-library has its own annotation run, with separate raw data and processed data.