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bioRxiv · 10.1101/2020.06.28.171587

Quantitative occupancy of myriad transcription factors from one DNase experiment enables efficient comparisons across conditions

Luo, K.·Zhong, J.·Safi, A.·Hong, L. K.·Tewari, A. K.·Song, L.·Reddy, T. E.·Ma, L.·Crawford, G. E.·Hartemink, A. J.
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Abstract

Over a thousand different transcription factors (TFs) bind with varying occupancy across the human genome. Chromatin immunoprecipitation (ChIP) can assay occupancy genome-wide, but only one TF at a time, limiting our ability to comprehensively observe the TF occupancy landscape, let alone quantify how it changes across conditions. We developed TOP, a Bayesian hierarchical regression framework, to profile genome-wide quantitative occupancy of numerous TFs using data from a single DNase-seq experiment. TOP is supervised, and its hierarchical structure allows it to predict the occupancy of any sequence-specific TF, even those never assayed with ChIP. We used TOP to profile the quantitative occupancy of nearly 1500 human TF motifs, and examined how their occupancies changed genome-wide in multiple contexts: across 178 cell types, over 12 hours of exposure to different hormones, and across the genetic backgrounds of 70 individuals. TOP enables cost-effective exploration of quantitative changes in the landscape of TF binding.

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Luo, K., Zhong, J., Safi, A., Hong, L. K., Tewari, A. K., Song, L., Reddy, T. E., Ma, L., Crawford, G. E., Hartemink, A. J.. 2020-06-29. Quantitative occupancy of myriad transcription factors from one DNase experiment enables efficient comparisons across conditions. https://doi.org/10.1101/2020.06.28.171587

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