Gauging Association Patterns of Chromosome Territories via Chromatic Median

Ding, Hu; Stojkovic, Branislav; Berezney, Ronald; Xu, Jinhui

doi:10.1109/cvpr.2013.171

Cited by 9 publications

(19 citation statements)

References 21 publications

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“…An integrated suite of in-house developed software [24] , [63] and a new 3D distance measurement program termed eFISHent were then applied to the collected images to generate an extensive database of distance measurements. A new data mining and pattern recognition algorithm termed the chromatic median [39] was then applied to determine whether there is an overall preferential organization of the CT interactions.…”

Section: Discussionmentioning

confidence: 99%

“…Differences in associations were found at both the cell type and cell cycle levels. Using a newly developed data mining algorithm termed the chromatic median [39] , probabilistic network models were generated for the global patterns of interchromosomal interactions of all 7 chromosome pairs. The preferred arrangements were strikingly different between 10A and WI38 in both G1 and S phases.…”

Section: Introductionmentioning

confidence: 99%

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Cell Type Specific Alterations in Interchromosomal Networks across the Cell Cycle

et al. 2014

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The interchromosomal organization of a subset of human chromosomes (#1, 4, 11, 12, 16, 17, and 18) was examined in G1 and S phase of human WI38 lung fibroblast and MCF10A breast epithelial cells. Radial positioning of the chromosome territories (CTs) was independent of gene density, but size dependent. While no changes in radial positioning during the cell cycle were detected, there were stage-specific differences between cell types. Each CT was in close proximity (interaction) with a similar number of other CT except the gene rich CT17 which had significantly more interactions. Furthermore, CT17 was a member of the highest pairwise CT combinations with multiple interactions. Major differences were detected in the pairwise interaction profiles of MCF10A versus WI38 including cell cycle alterations from G1 to S. These alterations in interaction profiles were subdivided into five types: overall increase, overall decrease, switching from 1 to ≥2 interactions, vice versa, or no change. A global data mining program termed the chromatic median determined the most probable overall association network for the entire subset of CT. This probabilistic interchromosomal network was nearly completely different between the two cell lines. It was also strikingly altered across the cell cycle in MCF10A, but only slightly in WI38. We conclude that CT undergo multiple and preferred interactions with other CT in the nucleus and form preferred -albeit probabilistic- interchromosomal networks. This network of interactions is altered across the cell cycle and between cell types. It is intriguing to consider the relationship of these alterations to the corresponding changes in the gene expression program across the cell cycle and in different cell types.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cell Type Specific Alterations in Interchromosomal Networks across the Cell Cycle

et al. 2014

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“…This problem was solved with the introduction of a geometric technique termed the Chromatic Median or CM, which uses combinatorial optimization to infer the common chromosome interaction pattern or network for the overall cell population. 248 While the GMG used integer linear programming and rounding techniques, the CM is more accurate and robust. It is based on a number of newer techniques, such as semidefinite programming, multilevel rounding, geometric peeling, and adaptive sampling.…”

Section: Studies Measuring Ct-interactions Based On Distances Betweenmentioning

confidence: 99%

“…One limitation of the GMG method was that it identified each homologous CT of a pair based on a slight difference in the apparent volumes of each homologous CT rather than their interchromosomal association differences. This problem was solved with the introduction of a geometric technique termed the Chromatic Median or CM, which uses combinatorial optimization to infer the common chromosome interaction pattern or network for the overall cell population . While the GMG used integer linear programming and rounding techniques, the CM is more accurate and robust.…”

Section: Introductionmentioning

confidence: 99%

“…It is based on a number of newer techniques, such as semidefinite programming, multilevel rounding, geometric peeling, and adaptive sampling . The CM technique results in much better approximation ratios and yields near optimal solutions in all tested random or real data sets . Figure illustrates the major steps of the CM to generate the most probable network of CT interchromosomal interactions.…”

Section: Introductionmentioning

confidence: 99%

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Chromosome territories and the global regulation of the genome

Fritz

Sehgal

Pliss

et al. 2019

Genes Chromosomes & Cancer

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Spatial positioning is a fundamental principle governing nuclear processes. Chromatin is organized as a hierarchy from nucleosomes to Mbp chromatin domains (CD) or topologically associating domains (TADs) to higher level compartments culminating in chromosome territories (CT). Microscopic and sequencing techniques have substantiated chromatin organization as a critical factor regulating gene expression. For example, enhancers loop back to interact with their target genes almost exclusively within TADs, distally located coregulated genes reposition into common transcription factories upon activation, and Mbp CDs exhibit dynamic motion and configurational changes in vivo. A longstanding question in the nucleus field is whether an interactive nuclear matrix provides a direct link between structure and function. The findings of nonrandom radial positioning of CT within the nucleus suggest the possibility of preferential interaction patterns among populations of CT. Sequential labeling up to 10 CT followed by application of computer imaging and geometric graph mining algorithms revealed cell‐type specific interchromosomal networks (ICN) of CT that are altered during the cell cycle, differentiation, and cancer progression. It is proposed that the ICN correlate with the global level of genome regulation. These approaches also demonstrated that the large scale 3‐D topology of CT is specific for each CT. The cell‐type specific proximity of certain chromosomal regions in normal cells may explain the propensity of distinct translocations in cancer subtypes. Understanding how genes are dysregulated upon disruption of the normal “wiring” of the nucleus by translocations, deletions, and amplifications that are hallmarks of cancer, should enable more targeted therapeutic strategies.

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Non‐Random Patterns in the Distribution of NOR‐Bearing Chromosome Territories in Human Fibroblasts: A Network Model of Interactions

Pliss

Fritz

Stojkovic

et al. 2014

Journal Cellular Physiology

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We present a 3-D mapping in WI38 human diploid fibroblast cells of chromosome territories (CT) 13,14,15,21, and 22, which contain the nucleolar organizing regions (NOR) and participate in the formation of nucleoli. The nuclear radial positioning of NOR-CT correlated with the size of chromosomes with smaller CT more interior. A high frequency of pairwise associations between NOR-CT ranging from 52% (CT13-21) to 82% (CT15-21) was detected as well as a triplet arrangement of CT15-21-22 (72%). The associations of homologous CT were significantly lower (24–36%). The arrangements of each pairwise CT varied from CT13-14 and CT13-22, which had a majority of cells with single associations, to CT13-15 and CT13-21 where a majority of cells had multiple interactions. In cells with multiple nucleoli, one of the nucleoli (termed “dominant”) always associated with a higher number of CT. Moreover, certain CT pairs more frequently contributed to the same nucleolus than to others. This nonrandom pattern suggests that a large number of the NOR-chromsomes are poised in close proximity during the postmitotic nucleolar recovery and through their NORs may contribute to the formation of the same nucleolus. A global data mining program termed the chromatic median determined the most probable interchromosomal arrangement of the entire NOR-CT population. This interactive network model was significantly above randomized simulation and was composed of 13 connections among the NOR-CT. We conclude that the NOR-CT form a global interactive network in the cell nucleus that may be a fundamental feature for the regulation of nucleolar and other genomic functions.

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Gauging Association Patterns of Chromosome Territories via Chromatic Median

Abstract: Computing accurate and robust organizational patterns of chromosome territories inside the cell nucleus is critical

Cited by 9 publications

References 21 publications

Cell Type Specific Alterations in Interchromosomal Networks across the Cell Cycle

Cell Type Specific Alterations in Interchromosomal Networks across the Cell Cycle

Chromosome territories and the global regulation of the genome

Non‐Random Patterns in the Distribution of NOR‐Bearing Chromosome Territories in Human Fibroblasts: A Network Model of Interactions

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