Assessing stationary distributions derived from chromatin contact maps.

BACKGROUND:The spatial configuration of chromosomes is essential to various cellular processes, notably gene regulation, while architecture related alterations, such as translocations and gene fusions, are often cancer drivers. Thus, eliciting chromatin conformation is important, yet challenging due to compaction, dynamics and scale. However, a variety of recent assays, in particular Hi-C, have generated new details of chromatin structure, spawning a number of novel biological findings. Many findings have resulted from analyses on the level of native contact data as generated by the assays. Alternatively, reconstruction based approaches often proceed by first converting contact frequencies into distances, then generating a three dimensional (3D) chromatin configuration that best recapitulates these distances. Subsequent analyses can enrich contact level analyses via superposition of genomic attributes on the reconstruction. But, such advantages depend on the accuracy of the reconstruction which, absent gold standards, is inherently difficult to assess. Attempts at accuracy evaluation have relied on simulation and/or FISH imaging that typically features a handful of low resolution probes. While newly advanced multiplexed FISH imaging offers possibilities for refined 3D reconstruction accuracy evaluation, availability of such data is limited due to assay complexity and the resolution thereof is appreciably lower than the reconstructions being assessed. Accordingly, there is demand for new methods of reconstruction accuracy appraisal. RESULTS:Here we explore the potential of recently proposed stationary distributions, hereafter StatDns, derived from Hi-C contact matrices, to serve as a basis for reconstruction accuracy assessment. Current usage of such StatDns has focussed on the identification of highly interactive regions (HIRs): computationally defined regions of the genome purportedly involved in numerous long-range intra-chromosomal contacts. Consistent identification of HIRs would be informative with respect to inferred 3D architecture since the corresponding regions of the reconstruction would have an elevated number of k nearest neighbors (kNNs). More generally, we anticipate a monotone decreasing relationship between StatDn values and kNN distances. After initially evaluating the reproducibility of StatDns across replicate Hi-C data sets, we use this implied StatDn - kNN relationship to gauge the utility of StatDns for reconstruction validation, making recourse to both real and simulated examples. CONCLUSIONS:Our analyses demonstrate that, as constructed, StatDns do not provide a suitable measure for assessing the accuracy of 3D genome reconstructions. Whether this is attributable to specific choices surrounding normalization in defining StatDns or to the logic underlying their very formulation remains to be determined

Modeling the Kinematics of Distant Galaxies

Evolution of galaxies is one of the most actual topics in astrophysics. Among the most important factors determining the evolution are two galactic components which are difficult or even impossible to detect optically: the gaseous disks and the dark matter halo. We use deep Hubble Space Telescope images to construct a two-component (bulge + disk) model for stellar matter distribution of galaxies. Properties of the galactic components are derived using a three-dimensional galaxy modeling software, which also estimates disk thickness and inclination angle. We add a gas disk and a dark matter halo and use hydrodynamical equations to calculate gas rotation and dispersion profiles in the resultant gravitational potential. We compare the kinematic profiles with the Team Keck Redshift Survey observations. In this pilot study, two galaxies are analyzed deriving parameters for their stellar components; both galaxies are found to be disk-dominated. Using the kinematical model, the gas mass and stellar mass ratio in the disk are estimated.Comment: 7 pages, 3 figures, accepted for publication in Baltic Astronom