- Publication Date:
- NSF-PAR ID:
- Journal Name:
- Frontiers in Molecular Biosciences
- Sponsoring Org:
- National Science Foundation
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Robinson, Peter (Ed.)Abstract Motivation Genomic DNA replicates according to a reproducible spatiotemporal program, with some loci replicating early in S phase while others replicate late. Despite being a central cellular process, DNA replication timing studies have been limited in scale due to technical challenges. Results We present TIGER (Timing Inferred from Genome Replication), a computational approach for extracting DNA replication timing information from whole genome sequence data obtained from proliferating cell samples. The presence of replicating cells in a biological specimen leads to non-uniform representation of genomic DNA that depends on the timing of replication of different genomic loci. Replication dynamics can hence be observed in genome sequence data by analyzing DNA copy number along chromosomes while accounting for other sources of sequence coverage variation. TIGER is applicable to any species with a contiguous genome assembly and rivals the quality of experimental measurements of DNA replication timing. It provides a straightforward approach for measuring replication timing and can readily be applied at scale. Availability and Implementation TIGER is available at https://github.com/TheKorenLab/TIGER. Supplementary information Supplementary data are available at Bioinformatics online
High-resolution reconstruction of spatial chromosome organizations from chromatin contact maps is highly demanded, but is hindered by extensive pairwise constraints, substantial missing data, and limited resolution and cell-type availabilities. Here, we present FLAMINGO, a computational method that addresses these challenges by compressing inter-dependent Hi-C interactions to delineate the underlying low-rank structures in 3D space, based on the low-rank matrix completion technique. FLAMINGO successfully generates 5 kb- and 1 kb-resolution spatial conformations for all chromosomes in the human genome across multiple cell-types, the largest resources to date. Compared to other methods using various experimental metrics, FLAMINGO consistently demonstrates superior accuracy in recapitulating observed structures with raises in scalability by orders of magnitude. The reconstructed 3D structures efficiently facilitate discoveries of higher-order multi-way interactions, imply biological interpretations of long-range QTLs, reveal geometrical properties of chromatin, and provide high-resolution references to understand structural variabilities. Importantly, FLAMINGO achieves robust predictions against high rates of missing data and significantly boosts 3D structure resolutions. Moreover, FLAMINGO shows vigorous cross cell-type structure predictions that capture cell-type specific spatial configurations via integration of 1D epigenomic signals. FLAMINGO can be widely applied to large-scale chromatin contact maps and expand high-resolution spatial genome conformations for diverse cell-types.
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Target search by an imported conjugative DNA element for a unique integration site along a bacterial chromosome during horizontal gene transfer
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