Phanstiel, D. H. | Search bioRxiv

bioRxiv2018

Coral: Clear and customizable visualization of human kinome data

Protein kinases represent one ofthe largest gene families in eukaryotes and play roles in a wide range of cell signaling processes and human diseases, making them attractive targets for drug development. The human kinome is extensively featured inhigh-throughput studiesgenerating genomic, proteomic, and kinase profiling data. Current tools for visualizing kinase data in the context of the human kinome superfamily are limited to encoding data through the addition of nodes to a low-resolution image of the kinome tree. We present Coral, a user-friendly interactive webapplication for visualizing both quantitative and qualitative data. Unlike previous tools, Coral can encode data in three features (node color, node size, and branchcolor), allowsthreemodesofkinomevisualization (the traditional kinome tree as well as radial and dynamic-force networks) and generates high-resolution scalable vector graphic files suitable for publication without the need for refinement in graphic editing software. Due to its user-friendly, interactive, and highly customizable design, Coral is broadly applicable to high-throughput studies of the human kinome. The source code and web application are available at github.com/dphansti/Coral. html and phanstiel-lab.med.unc.edu/Coral respectively.

bioinformatics↗

bioRxiv2017

Static And Dynamic DNA Loops Form AP-1 Bound Activation Hubs During Macrophage Development

The three-dimensional arrangement of the human genome comprises a complex network of structural and regulatory chromatin loops important for coordinating changes in transcription during human development. To better understand the mechanisms underlying context-specific 3D chromatin structure and transcription during cellular differentiation, we generated comprehensive in situ Hi-C maps of DNA loops during human monocyte-to-macrophage differentiation. We demonstrate that dynamic looping events are regulatory rather than structural in nature and uncover widespread coordination of dynamic enhancer activity at preformed and acquired DNA loops. Enhancer-bound loop formation and enhancer-activation of preformed loops represent two distinct modes of regulation that together form multi-loop activation hubs at key macrophage genes. Activation hubs connect 3.4 enhancers per promoter and exhibit a strong enrichment for Activator Protein 1 (AP-1) binding events, suggesting multi-loop activation hubs driven by cell-type specific transcription factors may represent an important class of regulatory chromatin structures for the spatiotemporal control of transcription.\n\nHIGHLIGHTSO_LIHigh resolution and high sensitivity of loop detection via deeply sequenced in situ Hi-C experiments during monocyte to macrophage differentiation (> 10 billion total reads)\nC_LIO_LIMulti-loop interaction communities identified surrounding key macrophage genes.\nC_LIO_LIMulti-loop communities connect dynamic enhancers through both static and newly acquired DNA loops, forming hubs of activation\nC_LIO_LIMacrophage activation hubs are enriched for AP-1 bound long-range enhancer interactions, suggesting cell-type specific TFs drive changes in 3D structure and transcription through regulatory DNA loops\nC_LI

genomics↗