Measuring the reproducibility and quality of Hi-C data

BACKGROUND: Hi-C is currently the most widely used assay to investigate the 3D organization of the genome and to study its role in gene regulation, DNA replication, and disease. However, Hi-C experiments are costly to perform and involve multiple complex experimental steps; thus, accurate methods for measuring the quality and reproducibility of Hi-C data are essential to determine whether the output should be used further in a study. RESULTS: Using real and simulated data, we profile the performance of several recently proposed methods for assessing reproducibility of population Hi-C data, including HiCRep, GenomeDISCO, HiC-Spector, and QuASAR-Rep. By explicitly controlling noise and sparsity through simulations, we demonstrate the deficiencies of performing simple correlation analysis on pairs of matrices, and we show that methods developed specifically for Hi-C data produce better measures of reproducibility. We also show how to use established measures, such as the ratio of intra- to interchromosomal interactions, and novel ones, such as QuASAR-QC, to identify low-quality experiments. CONCLUSIONS: In this work, we assess reproducibility and quality measures by varying sequencing depth, resolution and noise levels in Hi-C data from 13 cell lines, with two biological replicates each, as well as 176 simulated matrices. Through this extensive validation and benchmarking of Hi-C data, we describe best practices for reproducibility and quality assessment of Hi-C experiments. We make all software publicly available at http://github.com/kundajelab/3DChromatin_ReplicateQC to facilitate adoption in the community

Serum procalcitonin and CRP levels in non-alcoholic fatty liver disease: a case control study

<p>Abstract</p> <p>Background</p> <p>Both C reactive protein (CRP) and procalcitonin (PCT) are well known acute phase reactant proteins. CRP was reported to increase in metabolic syndrome and type-2 diabetes. Similarly altered level of serum PCT was found in chronic liver diseases and cirrhosis. The liver is considered the main source of CRP and a source of PCT, however, the serum PCT and CRP levels in non-alcoholic fatty liver disease (NAFLD) were not compared previously. Therefore we aimed to study the diagnostic and discriminative role of serum PCT and CRP in NAFLD.</p> <p>Methods</p> <p>Fifty NAFLD cases and 50 healthy controls were included to the study. Liver function tests were measured, body mass index was calculated, and insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Serum CRP was measured with nephalometric method. Serum PCT was measured with Kryptor based system.</p> <p>Results</p> <p>Serum PCT levels were similar in steatohepatitis (n 20) and simple steatosis (n 27) patients, and were not different than the control group (0.06 ± 0.01, 0.04 ± 0.01 versus 0.06 ± 0.01 ng/ml respectively). Serum CRP levels were significantly higher in simple steatosis, and steatohepatitis groups compared to healthy controls (7.5 ± 1.6 and 5.2 ± 2.5 versus 2.9 ± 0.5 mg/dl respectively p < 0.01). CRP could not differentiate steatohepatitis from simple steatosis. Beside, three patients with focal fatty liver disease had normal serum CRP levels.</p> <p>Conclusion</p> <p>Serum PCT was within normal ranges in patients with simple steatosis or steatohepatitis and has no diagnostic value. Serum CRP level was increased in NAFLD compared to controls. CRP can be used as an additional marker for diagnosis of NAFLD but it has no value in discrimination of steatohepatitis from simple steatosis.</p

Chromatin accessibility reveals insights into androgen receptor activation and transcriptional specificity

Abstract Background Epigenetic mechanisms such as chromatin accessibility impact transcription factor binding to DNA and transcriptional specificity. The androgen receptor (AR), a master regulator of the male phenotype and prostate cancer pathogenesis, acts primarily through ligand-activated transcription of target genes. Although several determinants of AR transcriptional specificity have been elucidated, our understanding of the interplay between chromatin accessibility and AR function remains incomplete. Results We used deep sequencing to assess chromatin structure via DNase I hypersensitivity and mRNA abundance, and paired these datasets with three independent AR ChIP-seq datasets. Our analysis revealed qualitative and quantitative differences in chromatin accessibility that corresponded to both AR binding and an enrichment of motifs for potential collaborating factors, one of which was identified as SP1. These quantitative differences were significantly associated with AR-regulated mRNA transcription across the genome. Base-pair resolution of the DNase I cleavage profile revealed three distinct footprinting patterns associated with the AR-DNA interaction, suggesting multiple modes of AR interaction with the genome. Conclusions In contrast with other DNA-binding factors, AR binding to the genome does not only target regions that are accessible to DNase I cleavage prior to hormone induction. AR binding is invariably associated with an increase in chromatin accessibility and, consequently, changes in gene expression. Furthermore, we present the first in vivo evidence that a significant fraction of AR binds only to half of the full AR DNA motif. These findings indicate a dynamic quantitative relationship between chromatin structure and AR-DNA binding that impacts AR transcriptional specificity

Geochemistry of free and dissolved gases in the Amik basin area (Turkey) and its relationships with the tectonic setting

Twenty-two gas samples were collected in August 2012 in the area of Amik basin (Turkey). Two samples were collected from gas seeps, one was a bubbling gas in a thermal spring, while the remaining were dissolved gases from cold and thermal groundwaters (T 16-43 °C). All gases were analysed for their chemical composition (He, H2, O2, N2, CH4 and CO2) and for their He isotopic composition. Dissolved gases were also analysed for the carbon isotopic composition of the total dissolved carbon (TDC), while free gases also for their higher hydrocarbon (C1 – C5) content and for D of H2 and CH4, 13C of CH4 Basing on their chemical composition, the gases can be roughly subdivided in three groups. Most of the dissolved gases (16) belonging to the first group were collected from springs or shallow wells (< 150 m depth). All these samples contain mainly atmospheric gasses with very limited H2 (< 80 ppm) and CH4 (1 – 2700 ppm) contents and minor concentrations of CO2 (0.5 – 11.2 %). The isotopic composition of TDC evidences an almost organic contribution. The only exception is represented by the CO2-richest sample where a small but significant mantle contribution is found. Such contribution can also be evidenced in its 3He rich isotopic composition. Further three samples of this group evidence a small mantle contribution. These samples were collected in the northern part of the basin along the main tectonic structures delimiting the basin and close to areas with quaternary volcanic activity. A second group is composed by two dissolved gases collected from deep boreholes (> 1200 m depth). Their composition is typical of hydrocarbon reservoirs being very rich in CH4 (> 78 %) and N2 (> 13%). Also the water composition is typical of saline connate waters (Cl- and B-rich, SO4-poor). C-isotopic composition of methane ( 13C -65% ) points to a biogenic origin while He-isotopic composition indicates a prevailing crustal signature for one (R/Ra 0.16) of the sites and small mantle contribution for the other (R/Ra 0.98). To the last group belong four gas samples taken at two sites within the ophiolitic basement that crops out west of the basin. These gases have the characteristic composition of gas generated by low temperature serpentinisation processes with high hydrogen (37 – 50 %) and methane (10 – 61 %) concentrations. While all gases show an almost identical D-H2 of -750h those of one of the two sites display an isotopic composition of methane ( 13C -5h D -105% ) and a C1/[C2+C3] ( 100) ratio typical of abiogenic hydrocarbons and mantle-type helium (R/Ra: 1.33), while those of the other site evidence a contribution of a crustal (thermogenic) component ( 13C-CH4 -30h D -325h C1/[C2+C3] 3000). Such crustal contribution is also supported by higher N2 contents (40% instead of 2%) and lower He-isotopic composition (R/Ra 0.07). The preliminary results highlight contributions of mantle-derived volatiles to the fluids vented along the Amik Basin. The main tectonic structure of the area, the Death Sea Fault, and other parallel structures crossing the basin seem to be the responsible for deep-originated volatiles drainage towards shallow levels

3D model for prediction of flow profiles around bridges

WOS: 000281759000013Computational fluid dynamics models have become well established as tools for simulating free surface flow over a wide range of structures. This study is an assessment and comparison of the performance of a commercially available three-dimensional numerical software, which solves the Reynolds-averaged Navier-Stokes equations, to predict the free surface profiles from up-to downstream of four different bridge types with and without piers in a compound channel. The model results were compared with the available experimental data. Comparisons indicate that the model provides a reasonably good description of free surface profiles under both gradually and rapidly varied flow conditions in the bridge vicinity, respectively