4DNvestigator: Time Series Genomic Data Analysis Toolbox

Lindsly, Stephen; Chen, Can; Lü, Sijia; Ronquist, Scott; Dilworth, Samuel; Perlman, Michael D.; Rajapakse, Indika

doi:10.1101/2020.01.08.898387

Cited by 7 publications

(20 citation statements)

References 34 publications

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“…In contrast, we observed a pronounced lack of ABE in crucial biological pathways and essential genes. Our findings highlight advantages of integrating genomics analyses in a cell cycle and allele-specific manner and represent an allele-specific extension of the 4D Nucleome (4DN) (20)(21)(22)(23). This approach will be beneficial to investigation of human phenotypic traits and their penetrance, genetic diseases, vulnerability to complex disorders, and tumorigenesis.…”

Section: Introductionmentioning

confidence: 87%

“…These matrices represent the local genomic architecture of the differentially expressed genes. To determine whether these local regions have changed in the seven comparisons, we used a method developed by Larntz and Perlman (25) which we refer to as the Larntz-Perlman (LP) procedure. This method determines the similarity of two correlation matrices, and outputs whether or not the matrices have statistically significant differences.…”

Section: Analysis Of Hi-c: a Hierarchy Of Organizationmentioning

confidence: 99%

“…This method determines the similarity of two correlation matrices, and outputs whether or not the matrices have statistically significant differences. To satisfy the conditions of the LP procedure, we used the correlation matrix of the log 2 -transformed Hi-C data (25). We applied the LP procedure to all genes that were differentially expressed in RNAseq (Bru-seq) and found that 627 (446) genes had at least one transition in which the expression and local architecture had both significantly changed.…”

Section: Analysis Of Hi-c: a Hierarchy Of Organizationmentioning

confidence: 99%

“…These matrices represent the local genomic structure of the differentially expressed genes, and are slightly smaller than average TAD size (∼1 Mb). We then compared the correlation matrices of the log 2 -transformed local Hi-C data and determined whether or not the matrices have statistically significant differences (p < 0.05) (23,51). We applied this comparison to all genes that were differentially expressed in RNA-seq (Bru-seq) and found that 515 (403) genes had at least one comparison in which both the expression and local structure had significantly changed.…”

Section: Allele-specific Genome Structurementioning

confidence: 99%

“…In network science, the relative importance of a node in a network is commonly determined using network centrality (59). For Hi-C data, we consider genomic loci as nodes and use network centrality to measure the importance of each locus at each cell cycle phase (23,61). We initially performed a global analysis of the maternal and paternal 4DN by combining RNA-seq with multiple network centrality measures (Supplemental Methods D) (23).…”

Section: The Maternal and Paternal 4d Nucleomementioning

confidence: 99%

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Functional Organization of the Maternal and Paternal Human 4D Nucleome

Lindsly

Jia

Chen

et al. 2020

Preprint

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Highlights• Structural and functional differences between the maternal and paternal genomes, including similar allelic bias in related subsets of genes.• Coupling between the dynamics of gene expression and genome architecture for specific alleles illuminates an allele specific 4D Nucleome.• A novel allele specific phasing algorithm for genome architecture and a quantitative framework for integration of gene expression and genome architecture. AbstractMillions of genetic variants exist between the paternal and maternal genomes in human cells (1, 2), which result in unequal allelic contributions to gene transcription (3, 4). However, it remains poorly understood how allelic bias affects the interplay between transcription and the 3D organization of the genome. We sought to understand how transcription and genome architecture differ between the maternal and paternal genomes across the cell cycle. We collected and analyzed haplotype-resolved genome-wide data from B-Lymphocytes (NA12878) in G1, S, and G2/M, using RNA sequencing (RNAseq), bromouridine sequencing (Bru-seq), and genome wide chromosome conformation capture (Hi-C). In the past, separation of allele specific data was done only through heterozygous single nucleotide variations (SNVs), insertions, and deletions (InDels), as these unique variations allowed DNA sequencing reads to be mapped back to their parental origins. In this paper, we introduce a novel method of phasing Hi-C data using reads assigned through SNVs/InDels to predict the parental origin of nearby reads of unknown origin. This method allows for more structural data to be systematically assigned to a parental origin, and therefore reduces the sparsity of the allele specific Hi-C contact matrices. By integrating allele specific RNA-seq, Bru-seq, and Hi-C data through three phases of the cell cycle, along with publicly available protein binding data, we provide a more comprehensive understanding of architectural and transcriptional differences between the two genomes. These analyses reveal specific patterns in allelic bias, including similar bias characteristics in some groups of related genes. The integration of these data enabled construction of an allele specific 4D Nucleome.

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Section: Introductionmentioning

confidence: 87%

Section: Analysis Of Hi-c: a Hierarchy Of Organizationmentioning

confidence: 99%

Section: Analysis Of Hi-c: a Hierarchy Of Organizationmentioning

confidence: 99%

Section: Allele-specific Genome Structurementioning

confidence: 99%

Section: The Maternal and Paternal 4d Nucleomementioning

confidence: 99%

See 3 more Smart Citations

Functional Organization of the Maternal and Paternal Human 4D Nucleome

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Jia

Chen

et al. 2020

Preprint

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Rearrangement of T Cell genome architecture regulates GVHD

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Unraveling three-dimensional chromatin structural dynamics during spermatogonial differentiation

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4DNvestigator: Time Series Genomic Data Analysis Toolbox

Cited by 7 publications

References 34 publications

Functional Organization of the Maternal and Paternal Human 4D Nucleome

Functional Organization of the Maternal and Paternal Human 4D Nucleome

Rearrangement of T Cell genome architecture regulates GVHD

Unraveling three-dimensional chromatin structural dynamics during spermatogonial differentiation

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