Abstract
Some of the most fundamental yet largely unresolved questions in genomic analysis revolve around how gene-regulatory “inputs” (e.g., binding by transcription factors or chromatin modifying enzymes at a certain DNA region) generate an “output” of mRNA expression. The development of new genomic technologies opens the way for addressing such questions in unprecedented detail. One recent example is Massively Parallel Reporter Assay, which allows for cost effective, high-throughput activity screening of thousands of synthetic regulatory DNA regions (promoters or enhancers). This nascent technology can be used to systematically probe the dependencies between regulatory “input” factors, thus opening the way for detailed models of combinatorial effects. Another recent technology, single-cell RNA-Seq provides a genome-scale view of cell-to-cell variability in mRNA expression. The ensuing data can be potentially utilized to calibrate models so as to capture the non-deterministic nature of transcriptional regulation. In this talk I will briefly present these two advances, discuss their potential to improve our ability to build accurate models of transcriptional regulation, and point out some of the challenges that lay ahead.