Genome-wide estimation of firing efficiencies of origins of DNA replication from time-course copy number variation data

<p>Abstract</p> <p>Background</p> <p>DNA replication is a fundamental biological process during S phase of cell division. It is initiated from several hundreds of origins along whole chromosome with different firing efficiencies (or frequency of usage). Direct measurement of origin firing efficiency by techniques such as DNA combing are time-consuming and lack the ability to measure all origins. Recent genome-wide study of DNA replication approximated origin firing efficiency by indirectly measuring other quantities related to replication. However, these approximation methods do not reflect properties of origin firing and may lead to inappropriate estimations.</p> <p>Results</p> <p>In this paper, we develop a probabilistic model - Spanned Firing Time Model (SFTM) to characterize DNA replication process. The proposed model reflects current understandings about DNA replication. Origins in an individual cell may initiate replication randomly within a time window, but the population average exhibits a temporal program with some origins replicated early and the others late. By estimating DNA origin firing time and fork moving velocity from genome-wide time-course S-phase copy number variation data, we could estimate firing efficiency of all origins. The estimated firing efficiency is correlated well with the previous studies in fission and budding yeasts.</p> <p>Conclusions</p> <p>The new probabilistic model enables sensitive identification of origins as well as genome-wide estimation of origin firing efficiency. We have successfully estimated firing efficiencies of all origins in S.cerevisiae, S.pombe and human chromosomes 21 and 22.</p

Transcriptomic Analyses of Sexual Dimorphism of the Zebrafish Liver and the Effect of Sex Hormones

10.1371/journal.pone.0053562PLoS ONE81

Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation

Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIAPET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells

Comparative analysis of the transcriptome across distant species

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters

Determination of River Ecological Base Flow Based on the Coupling Relationship of Sediment–Water Quality–Biodiversity in Water Shortage Area of Northwest China

Maintaining the integrity of ecosystem service functions of rivers has become the top issue in the water shortage area of Northwest China. By combining the coupling relationship of sediment, water quality, and biodiversity and the hydraulic relationship of the section, we established a quantitative calculation method for the river ecological base flow, which is mainly divided into the following three steps: first, we determined the reasonable ecological flow velocity range of rivers via water purification, maintaining the river geometry and biodiversity; second, we combined the hydraulic relationship between the river ecological velocity range and the river ecological base flow to determine the protection target of the river ecological base flow; finally, we combined the remaining water volume of rivers and ecological base flow protection target of rivers to determine their protection rate. Take the Baoji section of the Weihe River as an example: the results show that the ecological base flow in the Baoji section of the Weihe River is [6.26, 9.17 m3/s] and [32.94, 38.93 m3/s] from October of this year to May of next year and from June to September, respectively, and the protection rates of the ecological base flow for five typical years are 62.47%, 41.10%, 16.16%, 15.07%, and 10.68%. These coupling methods can also be used in the world’s river basin, which has similar problems

Adsorption Characteristics of Several Bioretention-Modified Fillers for Phosphorus

To optimize the bioretention mixed fillers with better removal of phosphorus, this paper studies the adsorption characteristics of single filler and modified mixed filler through static adsorption experiments, and adopts the dynamical mini-column experiments to examine the adsorption capacities of the soil and modified mixed fillers. Results show that, in the static adsorption experiments, both water treatment residual (WTR) and fly ash exhibit good adsorption capacity when used as a single filler and modifier. Adsorption capacity increases with increasing WTR and fly ash dosage in the mixed filler. The modified mixed filler with WTR exerts a clear effect in the dynamic adsorption experiment, which is unsaturated when influent phosphorus concentration is 1 mg/L and inflow amount is equivalent to 15 years of precipitation. The adsorption capacity of WTR is 3.5&ndash;4.5 times that of other mixed fillers. Fly ash as a modifier shows a poor dynamic adsorption effect and thus must be continuously studied. In this study, WTR is recommended as a bioretention phosphorus removal additive. In engineering applications, the amount of WTR added can be controlled within 5&ndash;10% (by mass) according to influent phosphorus concentration

Simulation of Rain Garden Effects in Urbanized Area Based on Mike Flood

An urban storm and surface water pollution model (MIKE FLOOD) was used to assess the impact of rain gardens on water quantity and quality for an urban area in Xi&rsquo;an. After the rain garden measures were added, the results show that: (1) In the case where the total proportion of rain gardens was 2%, the overflow reduction rate was 6.74% to 65.23%, the number of overflow points reduction rate was 1.79% to 65.63%, the overload pipes reduction rate was 0% to 11.15%, the runoff reduction rate was 1.93% to 9.69%; (2) Under different rainfall conditions, the load reduction rate of suspended solids (SS), chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) were 2.36% to 30.35%, 2.37% to 30.11%, 2.34% to 30.08%, and 2.32% to 31.35%, respectively; (3) The submersion ranges of different submerged depths and submerged durations were reduced by 0.30% to 64.18% and 7.12% to 100%, respectively. The statistics of the automatic modeling and intelligent analysis system (AMIAS) showed that the rain garden regulation range of the waterlogging risk area was 0.78% to 100%. The rain garden has a good control effect on urban storm runoff in terms of water volume and water quality, but as the rainfall recurrence interval increases, the control effect will decrease

Temporal–Spatial Variations in the Economic Value Produced by Environmental Flows in a Water Shortage Area in Northwest China

Scientific and accurate assessments of the economic value produced by environmental flows are an important basis for the protection of environmental flows by means of economics. Because of the temporal and spatial variation characteristics of environmental flows, it is more appropriate to study the economic value produced by environmental flows using a temporal–spatial scale rather than static calculations. In the present study, we combine the major influencing factors to establish the temporal–spatial calculation methods of the economic value produced by environmental flows using the assessment techniques of resources and environmental economics. The results obtained for the Wei River show that the annual variation range of the total economic value is CNY 0.30–0.42 billion, and the unit economic value is 0.86–6.40 CNY/m3 during the non-flood season ranging from the years 1980 to 2017. In general, the monthly variation in the total economic value ranges from CNY 0.04 to 0.08 billion, and the unit economic value is 0.94–14.34 CNY/m3. Based on this result, the variation tendency of the total economic value is consistent with the changing trend of the environmental flows occurring in the river; however, the unit economic value presents a reverse pattern. Furthermore, the deficiency of environmental flows can lead to a significant increase in its unit economic value. This method presents a dynamic, small temporal–spatial scale assessment of the economic value produced by environmental flows. It can also provide theoretical support for the ecological compensation of environmental flow protection in rivers present in water shortage areas