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

Photometric redshift galaxies as tracers of the filamentary network

Galaxy filaments are the dominant feature in the overall structure of the cosmic web. The study of the filamentary web is an important aspect in understanding galaxy evolution and the evolution of matter in the Universe. A map of the filamentary structure is an adequate probe of the web. We propose that photometric redshift galaxies are significantly positively associated with the filamentary structure detected from the spatial distribution of spectroscopic redshift galaxies. The catalogues of spectroscopic and photometric galaxies are seen as point-process realisations in a sphere, and the catalogue of filamentary spines is proposed to be a realisation of a random set in a sphere. The positive association between these sets was studied using a bivariate $J-$function, which is a summary statistics studying clustering. A quotient $D$ was built to estimate the distance distribution of the filamentary spine to galaxies in comparison to the distance distribution of the filamentary spine to random points in $3-$dimensional Euclidean space. This measure gives a physical distance scale to the distances between filamentary spines and the studied sets of galaxies. The bivariate $J-$function shows a statistically significant clustering effect in between filamentary spines and photometric redshift galaxies. The quotient $D$ confirms the previous result that smaller distances exist with higher probability between the photometric galaxies and filaments. The trend of smaller distances between the objects grows stronger at higher redshift. Additionally, the quotient $D$ for photometric galaxies gives a rough estimate for the filamentary spine width of about $1$~Mpc. Photometric redshift galaxies are positively associated with filamentary spines detected from the spatial distribution of spectroscopic galaxies.Comment: Accepted to Astronomy & Astrophysics. 13 pages and 9 figure