The Properties of Genome Conformation and Spatial Gene Interaction and Regulation Networks of Normal and Malignant Human Cell Types

In this work, we generated hundreds of millions of Hi-C paired end sequence reads for three different human cells (RL follicular lymphoma cell line, primary tumor B-cells from an acute lymphoblastic leukemia patient, and MHH-CALL-4 B-cell acute lymphoblastic leukemia cell line) using the Hi-C technique. An in-house Bioinformatics software pipeline was developed and applied to map sequence reads to the human reference genome, producing a large data set of high-quality and high-resolution chromosome contacts. Our computational analysis on these data reveal some interesting properties of human genome conformation, including conformational conservation and variation of the genomes of different cells, intra- and inter-chromosomal interactions, aberrant chromosomal translocation, spatial gene clusters, spatial gene-gene interactions, and spatial gene-regulatory-element interaction. Furthermore, we derived spatial interactions between functional elements (genes, transcription factor binding sites) from the chromosomal interaction data. The data were then used to generate chromosome-/genome-wide gene-gene interaction networks, transcription factor binding site (TFBS) – TFBS networks, and gene-TFBS networks. Remarkably, the connectivity in both networks shows the hallmark features of scale-free networks, suggesting that spatial interactions of gene-gene, gene-TFBS, and TFBS-TFBS in a genome are far from random. Overall design: Three different human cells (RL follicular lymphoma cell line, primary tumor B-cells from an acute lymphoblastic leukemia patient, and MHH-CALL-4 B-cell acute lymphoblastic leukemia cell line) were analyzed