Hi-C data reveals regions of the genome in close proximity

Juicebox plot showing the contact frequency map (100kb resolution) for the entire genome with each chromosome laid end to end (X and Y chromosomes at the bottom right). Each red dot consists of two regions of the genome associated with each other. Top right: HC patient monocytes. Bottom Left: AH patient monocytes

Summary of Clinical data for patient samples used for Hi-C

Correlation reveals differences between AH and HC

Hierarchically clustered heatmaps of correlation coefficients of the Hi-C data for each chromosome. For each heatmap, darker colors refer to higher correlation coefficients.

Changes in Contact Frequency in Disease are Local and Long-Range

Plots showing regions with significant changes in contact frequency in AH. Each dot indicates two regions of the genome that either increased (Blue) or decreased (Red) contact frequency in AH. X- and Y-axes are position along the chromosome

Certain Regions in the Genome have Hotspots of Significant Change in Disease

Manhattan plot showing regions of the genome with significant changes in chromatin interaction with disease. X-axis is position along the chromosome. Y-axis is –log10(p).

Locations and gene contents of hotspots with significant change in AH

CXC-chemokine cluster has increase contact frequency within the TAD and reduced outside

A) Schematic of the CXC-chemokine gene cluster. B) Juicebox plot showing contact frequency map of the CXC-chemokine gene cluster and the surrounding genomic region. Blue boxes are 100kb regions significantly different in disease. C) Plot corresponding to the Juicebox plot showing whether each significant region increased (Blue) or decreased (Red) contact frequency in disease.

Myeloid CLR gene cluster has increased local contacts in AH

A) Schematic of the NK-gene receptor complex. B) Juicebox plot showing contact frequency map of the NK-gene receptor complex and the surrounding genomic region. Blue boxes are 100kb regions significantly different in disease. C) Plot corresponding to the Juicebox plot showing whether each significant region increased (Blue) or decreased (Red) contact frequency in disease.

Genomic region around IL-22 and IFNG have decreased local contacts in AH

A) Juicebox plot showing contact frequency map of the region on Chromosome 12 around the IL-22 and IFNG genes. Blue boxes are regions significantly different in disease. B) Plot corresponding to the Juicebox plot showing whether each significant region increased (Blue) or decreased (Red) contact frequency in disease.

The Split CC-Chemokine Cluster has increased contact between loci, and highly correlated expression in AH

A) Juicebox plot showing contact frequency map of the NK-gene receptor complex and the surrounding genomic region. Blue boxes are regions significantly different in disease. B) Plot corresponding to the Juicebox plot showing whether each significant region increased (Blue) or decreased (Red) contact frequency in disease. C/D) Correlation analysis showing coordinately expressed in response to LPS (100pg/ml, for 24 hours) for healthy control (C) and AH (D). Genes are organized by chromosomal position and oriented in the same manner as A and B. Blue squares indicate genes with highly correlated expression while red squares indicate anti-correlated expression.