4D nucleome Analysis Toolbox: analysis of Hi-C data with abnormal karyotype and time series capabilities

Seaman, Laura; Rajapakse, Indika

doi:10.1093/bioinformatics/btx484

Cited by 7 publications

(9 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Analysis of Hi-C Matrices. Hi-C matrices were normalized, plotted, and analyzed in conjunction with RNA-seq data for cell lines using the 4D Nucleome Analysis Toolbox (4D-NAT) described by Seaman and colleagues (26).…”

Section: Nucleome Analysismentioning

confidence: 99%

Biomaterial Scaffolds Recruit an Aggressive Population of Metastatic Tumor Cells In Vivo

et al. 2019

Self Cite

View full text Add to dashboard Cite

For most cancers, metastasis is the point at which clinical treatment shifts from curative intent to extending survival. Biomaterial implants acting as a synthetic premetastatic niche recruit metastatic cancer cells and provide a survival advantage, and their use as a diagnostic platform requires assessing their relevance to disease progression. Here, we showed that scaffold-captured tumor cells (SCAF) were 30 times more metastatic to the lung than primary tumor (PT) cells, similar to cells derived from lung micrometastases (LUNG). SCAF cells were more aggressive in vitro, demonstrated higher levels of migration, invasion, and mammosphere formation, and had a greater proportion of cancer stem cells than PT. SCAF cells were highly enriched for gene expression signatures associated with metastasis and had associated genomic structural changes, including globally enhanced entropy. Collectively, our findings demonstrate that SCAF cells are distinct from PT and more closely resemble LUNG, indicating that tumor cells retrieved from scaffolds are reflective of cells at metastatic sites.

show abstract

Section: Nucleome Analysismentioning

confidence: 99%

Biomaterial Scaffolds Recruit an Aggressive Population of Metastatic Tumor Cells In Vivo

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…The first methods developed to call TADs were based on one-dimensional scores. The directionality index (DI) calculates for each bin the degree of upstream and downstream interaction biases and is segmented with a hidden Markov model (HMM) to derive TADs in DomainCaller (Dixon et al 2012 ) and the 4D Nucleome Analysis Toolbox (Seaman and Rajapakse 2018 ). Instead, the insulation score quantifies the interactions passing across each genomic bin, and it allows defining boundaries by identifying local minima (Crane et al 2015 ), also implemented in Cworld ( https://github.com/dekkerlab/cworld-dekker ).…”

Section: Downstream Analysesmentioning

confidence: 99%

Hi-C analysis: from data generation to integration

2018

View full text Add to dashboard Cite

In the epigenetics field, large-scale functional genomics datasets of ever-increasing size and complexity have been produced using experimental techniques based on high-throughput sequencing. In particular, the study of the 3D organization of chromatin has raised increasing interest, thanks to the development of advanced experimental techniques. In this context, Hi-C has been widely adopted as a high-throughput method to measure pairwise contacts between virtually any pair of genomic loci, thus yielding unprecedented challenges for analyzing and handling the resulting complex datasets. In this review, we focus on the increasing complexity of available Hi-C datasets, which parallels the adoption of novel protocol variants. We also review the complexity of the multiple data analysis steps required to preprocess Hi-C sequencing reads and extract biologically meaningful information. Finally, we discuss solutions for handling and visualizing such large genomics datasets.

show abstract

“…In addition to robust‐omics analysis including RNA‐seq, emerging 4D Nucleome algorithms demonstrate the potential application to pharmacogenomics . Clinical colonoscopy biopsies can be used to isolate intact crypts with the structure similar to gastrulation as mentioned by Turing .…”

Section: Some Potential Applications Of Turing Pattern Analysis In Gamentioning

confidence: 99%

Hypothesis: Caco‐2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts

Zheng

Kalinin

Dinov

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

Colon crypts are recognized as a mechanical and biochemical Turing patterning model. Colon epithelial Caco‐2 cell monolayer demonstrated 2D Turing patterns via force analysis of apical tight junction live cell imaging which illuminated actomyosin meshwork linking the actomyosin network of individual cells. Actomyosin forces act in a mechanobiological manner that alters cell/nucleus/tissue morphology. We observed the rotational motion of the nucleus in Caco‐2 cells that appears to be driven by actomyosin during the formation of a differentiated confluent epithelium. Single‐ to multi‐cell ring/torus‐shaped genomes were observed prior to complex fractal Turing patterns extending from a rotating torus centre in a spiral pattern consistent with a gene morphogen motif. These features may contribute to the well‐described differentiation from stem cells at the crypt base to the luminal colon epithelium along the crypt axis. This observation may be useful to study the role of mechanogenomic processes and the underlying molecular mechanisms as determinants of cellular and tissue architecture in space and time, which is the focal point of the 4D nucleome initiative. Mathematical and bioengineer modelling of gene circuits and cell shapes may provide a powerful algorithm that will contribute to future precision medicine relevant to a number of common medical disorders.

show abstract

4D nucleome Analysis Toolbox: analysis of Hi-C data with abnormal karyotype and time series capabilities

Abstract: indikar@umich.edu.

Cited by 7 publications

References 9 publications

Biomaterial Scaffolds Recruit an Aggressive Population of Metastatic Tumor Cells In Vivo

Biomaterial Scaffolds Recruit an Aggressive Population of Metastatic Tumor Cells In Vivo

Hi-C analysis: from data generation to integration

Hypothesis: Caco‐2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts

Contact Info

Product

Resources

About