CIRCpedia v2: An Updated Database for Comprehensive Circular RNA Annotation and Expression Comparison

Circular RNAs (circRNAs) from back-splicing of exon(s) have been recently identified to be broadly expressed in eukaryotes, in tissue- and species-specific manners. Although functions of most circRNAs remain elusive, some circRNAs are shown to be functional in gene expression regulation and potentially relate to diseases. Due to their stability, circRNAs can also be used as biomarkers for diagnosis. Profiling circRNAs by integrating their expression among different samples thus provides molecular basis for further functional study of circRNAs and their potential application in clinic. Here, we report CIRCpedia v2, an updated database for comprehensive circRNA annotation from over 180 RNA-seq datasets across six different species. This atlas allows users to search, browse, and download circRNAs with expression features in various cell types/tissues, including disease samples. In addition, the updated database incorporates conservation analysis of circRNAs between humans and mice. Finally, the web interface also contains computational tools to compare circRNA expression among samples. CIRCpedia v2 is accessible at http://www.picb.ac.cn/rnomics/circpedia.     

A Comprehensive Molecular Interaction Map for Rheumatoid Arthritis

Background

Computational biology contributes to a variety of areas related to life sciences and, due to the growing impact of translational medicine - the scientific approach to medicine in tight relation with basic science -, it is becoming an important player in clinical-related areas. In this study, we use computation methods in order to improve our understanding of the complex interactions that occur between molecules related to Rheumatoid Arthritis (RA).

Methodology

Due to the complexity of the disease and the numerous molecular players involved, we devised a method to construct a systemic network of interactions of the processes ongoing in patients affected by RA. The network is based on high-throughput data, refined semi-automatically with carefully curated literature-based information. This global network has then been topologically analysed, as a whole and tissue-specifically, in order to translate the experimental molecular connections into topological motifs meaningful in the identification of tissue-specific markers and targets in the diagnosis, and possibly in the therapy, of RA.

Significance

We find that some nodes in the network that prove to be topologically important, in particular AKT2, IL6, MAPK1 and TP53, are also known to be associated with drugs used for the treatment of RA. Importantly, based on topological consideration, we are also able to suggest CRKL as a novel potentially relevant molecule for the diagnosis or treatment of RA. This type of finding proves the potential of in silico analyses able to produce highly refined hypotheses, based on vast experimental data, to be tested further and more efficiently. As research on RA is ongoing, the present map is in fieri, despite being -at the moment- a reflection of the state of the art. For this reason we make the network freely available in the standardised and easily exportable .xml CellDesigner format at ‘www.picb.ac.cn/ClinicalGenomicNTW/temp.html’ and ‘www.celldesigner.org’.     

The Rabs: A family at the root of metazoan evolution

This paper is a response to Pecinka A, Fang W, Rehmsmeier M, Levy AA, Mittelsten Scheid, O: Polyploidization increases meiotic recombination frequency in Arabidopsis. BMC Biology 2011, 9:24. See research article at http://www.biomedcentral.com/1741-7007/9/24     

HeteroMeth: A Database of Cell-to-cell Heterogeneity in DNA Methylation

DNA methylation is an important epigenetic mark that plays a vital role in gene expression and cell differentiation. The average DNA methylation level among a group of cells has been extensively documented. However, the cell-to-cell heterogeneity in DNA methylation, which reflects the differentiation of epigenetic status among cells, remains less investigated. Here we established a gold standard of the cell-to-cell heterogeneity in DNA methylation based on single-cell bisulfite sequencing (BS-seq) data. With that, we optimized a computational pipeline for estimating the heterogeneity in DNA methylation from bulk BS-seq data. We further built HeteroMeth, a database for searching, browsing, visualizing, and downloading the data for heterogeneity in DNA methylation for a total of 141 samples in humans, mice, Arabidopsis, and rice. Three genes are used as examples to illustrate the power of HeteroMeth in the identification of unique features in DNA methylation. The optimization of the computational strategy and the construction of the database in this study complement the recent experimental attempts on single-cell DNA methylomes and will facilitate the understanding of epigenetic mechanisms underlying cell differentiation and embryonic development. HeteroMeth is publicly available at http://qianlab.genetics.ac.cn/HeteroMeth.     

An efficient survey method for estimating populations of Marsh Tits Poecile palustris,a low-density woodland passerine

Capsule: A playback survey comprising two visits to woodland in early spring can reliably detect Marsh Tits Poecile palustris and permit reasonable estimation of the number of territories.

Aims: To assess the efficacy of an efficient survey method for detecting and estimating populations of Marsh Tits.

Methods: Detection probability of colour-marked Marsh Tits, surveyed using playback, was assessed with Cormack–Jolly–Seber models. Reliability of territory estimates was compared between colour-marked and largely or wholly unmarked populations.

Results: Playback surveys over two visits in early spring were highly effective in detecting individual Marsh Tits. Territory estimates were similar for woods in years where less than 20% of the population was marked compared to years when a higher proportion of birds were colour-marked, although territories may be underestimated in larger woods with unmarked populations.

Conclusion: A playback survey comprising two visits in early spring is recommended as an efficient method of surveying Marsh Tit populations and locating individuals. A survey protocol is suggested.     

iKcr-PseEns: Identify lysine crotonylation sites in histone proteins with pseudo components and ensemble classifier

Lysine crotonylation (Kcr) is an evolution-conserved histone posttranslational modification (PTM), occurring in both human somatic and mouse male germ cell genomes. It is important for male germ cell differentiation. Information of Kcr sites in proteins is very useful for both basic research and drug development. But it is time-consuming and expensive to determine them by experiments alone. Here, we report a novel predictor called iKcr-PseEns that is established by incorporating five tiers of amino acid pairwise couplings into the general pseudo amino acid composition. It has been observed via rigorous cross-validations that the new predictor's sensitivity (Sn), specificity (Sp), accuracy (Acc), and stability (MCC) are 90.53%, 95.27%, 94.49%, and 0.826, respectively. For the convenience of most experimental scientists, a user-friendly web-server for iKcr-PseEns has been established at http://www.jci-bioinfo.cn/iKcr-PseEns, by which users can easily obtain their desired results without the need to go through the complicated mathematical equations involved.     

基层医疗机构人才队伍建设的探讨

??????? 在医改中硬件是基础,软件是根本,基层医疗机构人才队伍建设问题至关重要,本文就如何吸引毕业生下沉到基层、如何提升基层现存医疗队伍的技术水平提出建议,并为如何实现2020年培养30万名全科医生的总体目标,提出利用社会融资方法培养农村全科医生的构想。     

RADtyping: An Integrated Package for Accurate De Novo Codominant and Dominant RAD Genotyping in Mapping Populations

Genetic linkage maps are indispensable tools in genetic, genomic and breeding studies. As one of genotyping-by-sequencing methods, RAD-Seq (restriction-site associated DNA sequencing) has gained particular popularity for construction of high-density linkage maps. Current RAD analytical tools are being predominantly used for typing codominant markers. However, no genotyping algorithm has been developed for dominant markers (resulting from recognition site disruption). Given their abundance in eukaryotic genomes, utilization of dominant markers would greatly diminish the extensive sequencing effort required for large-scale marker development. In this study, we established, for the first time, a novel statistical framework for de novo dominant genotyping in mapping populations. An integrated package called RADtyping was developed by incorporating both de novo codominant and dominant genotyping algorithms. We demonstrated the superb performance of RADtyping in achieving remarkably high genotyping accuracy based on simulated and real mapping datasets. The RADtyping package is freely available at http://www2.ouc.edu.cn/mollusk/ detailen.asp?id=727.     

PEAS V1.0: a package for elementary analysis of SNP data

We have developed a software package named PEAS to facilitate analyses of large data sets of single nucleotide polymorphisms (SNPs) for population genetics and molecular phylogenetics studies. PEAS reads SNP data in various formats as input and is versatile in data formatting; using PEAS, it is easy to create input files for many popular packages, such as STRUCTURE, frappe, Arlequin, Haploview, LDhat, PLINK, EIGENSOFT, PHASE, fastPHASE, MEGA and PHYLIP. In addition, PEAS fills up several analysis gaps in currently available computer programs in population genetics and molecular phylogenetics. Notably, (i) It calculates genetic distance matrices with bootstrapping for both individuals and populations from genome-wide high-density SNP data, and the output can be streamlined to MEGA and PHYLIP programs for further processing; (ii) It calculates genetic distances from STRUCTURE output and generates MEGA file to reconstruct component trees; (iii) It provides tools to conduct haplotype sharing analysis for phylogenetic studies based on high-density SNP data. To our knowledge, these analyses are not available in any other computer program. PEAS for Windows is freely available for academic users from http://www.picb.ac.cn/~xushua/index.files/Download_PEAS.htm.     

Morphological and sexual traits in Atlas and Iberian Pied Flycatchers Ficedula hypoleuca speculigera and F. h. iberiae: a comparison

Capsule: There are significant biometric differences between Pied Flycatchers from Iberian and north African populations which are consistent with proposals to classify the two forms into separate species.

Aims: To determine the similarities and differences in the main biometrical and plumage sex traits between populations of the Iberian Pied Flycatcher Ficedula hypoleuca iberiae and the Atlas Flycatcher Ficedula hypoleuca speculigera.

Methods: Biometric and plumage traits of 193 breeding individuals of Iberian Pied Flycatchers and 43 Atlas Flycatchers were measured in 2014 with standardized protocols.

Results: Both sexes of Atlas Flycatchers were larger than Iberian Pied Flycatchers in skeletal (tarsus) and wing size and also differed in bill morphology, which was wider but shallower in speculigera than iberiae, with females (but not males) having shorter bills than iberiae females. Males differed in mantle colour and forehead patch size, with speculigera males being darker and displaying larger forehead patches than iberiae males. As in populations of iberiae, some speculigera females also expressed a white forehead patch.

Conclusion: We demonstrate significant phenotypic differences between Iberian Pied Flycatchers and Atlas Flycatchers with respect to size and traits of ecological and evolutionary relevance, supporting the recently proposed scenarios on their independent evolution.     

A Continuous Correlated Beta Process Model for Genetic Ancestry in Admixed Populations

Admixture and recombination create populations and genomes with genetic ancestry from multiple source populations. Analyses of genetic ancestry in admixed populations are relevant for trait and disease mapping, studies of speciation, and conservation efforts. Consequently, many methods have been developed to infer genome-average ancestry and to deconvolute ancestry into continuous local ancestry blocks or tracts within individuals. Current methods for local ancestry inference perform well when admixture occurred recently or hybridization is ongoing, or when admixture occurred in the distant past such that local ancestry blocks have fixed in the admixed population. However, methods to infer local ancestry frequencies in isolated admixed populations still segregating for ancestry do not exist. In the current paper, I develop and test a continuous correlated beta process model to fill this analytical gap. The method explicitly models autocorrelations in ancestry frequencies at the population-level and uses discriminant analysis of SNP windows to take advantage of ancestry blocks within individuals. Analyses of simulated data sets show that the method is generally accurate such that ancestry frequency estimates exhibited low root-mean-square error and were highly correlated with the true values, particularly when large (±10 or ±20) SNP windows were used. Along these lines, the proposed method outperformed post hoc inference of ancestry frequencies from a traditional hidden Markov model (i.e., the linkage model in structure), particularly when admixture occurred more distantly in the past with little on-going gene flow or was followed by natural selection. The reliability and utility of the method was further assessed by analyzing genetic ancestry in an admixed human population (Uyghur) and three populations from a hybrid zone between Mus domesticus and M. musculus. Considerable variation in ancestry frequencies was detected within and among chromosomes in the Uyghur, with a large region of excess French ancestry harboring a gene with a known disease association. Similar variation was detected in the mouse hybrid zone, with notable constancy in regions of excess ancestry among admixed populations. By filling what has been an analytical gap, the proposed method should be a useful tool for many biologists. A computer program (popanc), written in C++, has been developed based on the proposed method and is available on-line at http://sourceforge.net/projects/popanc/.     

Development of universal genetic markers based on single-copy orthologous (COSII) genes in Poaceae

Key message

We develop a set of universal genetic markers based on single-copy orthologous (COSII) genes in Poaceae.

Abstract

Being evolutionary conserved, single-copy orthologous (COSII) genes are particularly useful in comparative mapping and phylogenetic investigation among species. In this study, we identified 2,684 COSII genes based on five sequenced Poaceae genomes including rice, maize, sorghum, foxtail millet, and brachypodium, and then developed 1,072 COSII markers whose transferability and polymorphism among five bamboo species were further evaluated with 46 pairs of randomly selected primers. 91.3 % of the 46 primers obtained clear amplification in at least one bamboo species, and 65.2 % of them produced polymorphism in more than one species. We also used 42 of them to construct the phylogeny for the five bamboo species, and it might reflect more precise evolutionary relationship than the one based on the vegetative morphology. The results indicated a promising prospect of applying these markers to the investigation of genetic diversity and the classification of Poaceae. To ease and facilitate access of the information of common interest to readers, a web-based database of the COSII markers is provided (http://www.sicau.edu.cn/web/yms/PCOSWeb/PCOS.html).     

Breeding origins and pattern of migration of Bluethroats Luscinia svecica wintering from Iberia to Senegal as revealed by stable isotopes

Capsule: Stable isotope analyses reveal some degree of migratory connectivity of Bluethroat populations wintering from Iberia to West Africa.

Aims: To identify the probable breeding origins of Bluethroats wintering from Iberia to Senegal.

Methods: Bluethroat feathers (P1) were sampled from individuals at their wintering areas. These feathers were then analysed for stable H isotopes (δ²H). We assigned individual Bluethroats to approximate geographic origin using likelihood-based assignment procedures.

Results: We observed spatial segregation between different Bluethroat populations. At wintering sites north of the Sahara Desert, Bluethroats wintering to the west came from further west origins than those which overwintered to the east. Bluethroats from central-eastern Europe overwintered either within the circum-Mediterranean region or in Senegal. We found no clear evidence supporting a sub-Saharan wintering range for birds breeding in Iberia (Luscinia svecica azuricollis subspecies).

Conclusion: North of the Sahara Desert, we found what might be a parallel migration pattern. The apparent lack of Luscinia svecica namnetum Bluethroats in Senegal suggests to some extent some kind of leap-frog migration between some Luscinia svecica cyanecula populations and the L. s. namnetum subspecies.     

CCGD-ESCC: A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population

Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.     

Plant sex and phenological stage affect interactions with rhizosphere nematode communities

Background: In dioecious plants, females and males associate differently with mycorrhizal fungi, but interactions with other rhizosphere organisms are less well studied.

Aims: We investigated the effect of plant sex on rhizosphere nematode communities associated with Corema album, a dioecious shrub occurring in coastal habitats.

Methods: Rhizosphere samples were collected from males and females in three populations (150 plants), during fruiting and flowering. Nematode communities were characterised and compared between plant sexes through statistical analyses of the abundance of trophic groups, plant parasitic nematode (PPN) genera and ecological indices.

Results: Free-living nematodes showed no statistically significant differences owing to plant sex. Conversely, PPN community composition was significantly different between plant sexes during fruiting but not flowering, suggesting that physiological requirements over the annual phenological cycle of the plant influence ecological interactions with the rhizosphere.

Of the 13 PPN genera identified, the ectoparasitic Criconema and Hemicriconemellawere more abundant in the rhizosphere of males during fruiting, whereas the endoparasitic Meloidogyne associated more frequently with females, suggesting that plant host suitability is related to PPN feeding strategy.

Conclusions: It appears that interactions of individuals of different sexes of C. album with the rhizosphere nematode community vary with phenological stage, especially for PPN.     

Limited prospecting behaviour of juvenile Eagle Owls Bubo bubo during natal dispersal: implications for conservation

Capsule Features of the breeding population and temporary settlement area influence the behaviour of Eagle Owls Bubo bubo prospecting for breeding sites during natal dispersal.

Aims To understand how prospecting behaviour during natal dispersal is affected by (i) the main characteristics of the breeding and dispersing portions of the population and (ii) main prey availability.

Methods We explored the ten-year dynamics and characteristics of radio-tagged breeders and dispersers of an Eagle Owl population.

Results During the first years following natal dispersal there was little prospecting behaviour of nesting sites and birds remained mainly within non-breeding settlement areas, bordering the sector occupied by the breeding population. Settlement areas had an abundant food supply, and low intraspecific competition and mortality. We suggest that these features of the settlement areas may reduce the willingness of individuals to search for breeding sites and may have the potential to impact on the viability of breeding populations.

Conclusion From a conservation perspective, the lengthy use of the temporary settlement areas by juvenile Eagle Owls suggests that the sites should be considered as important as the breeding areas when planning conservation strategies. Reducing juvenile mortality in settlement areas may represent an overlooked conservation strategy for long-lived species and may have a crucial effect on the viability some animal populations.     

The role of recruitment and dispersal limitation in tree community assembly in Amazonian forests

Background: Species composition of plant communities is shaped by the interplay between dispersal limitation, environmental filters and stochastic events.

Aims: The aim of this work was to investigate the effects of dispersal limitation and environmental filtering on tree recruitment. To accomplish this, we employed the unified neutral theory of biodiversity and biogeography to examine migration within the metacommunity, defined as a set of interacting local communities linked by the dispersal of multiple potentially interacting species.

Methods: We sampled 12,975 individuals with dbh ≥ 1 cm in 26 1-ha permanent plots, including habitats of terra firme, transitional forests, várzea and campinarana, on the upper Madeira River, Brazilian Amazon.

Results: Campinarana drew individuals from outside the metacommunity species pool at a mean probability of recruitment of 0.06, a much lower probability than terra firme (0.31), transitional (0.21) and várzea forests (0.22). Environmental variables, such as water table depth, soil texture and fertility, were related to differences in community assembly.

Conclusions: Species abundance distribution and diversity patterns of plant assemblages in a large river landscape in the Amazon highlight the importance of environmental heterogeneity that conditions beta-diversity. The high variation in recruitment probabilities from the metacommunity species pool to local communities suggests high habitat variability in the process of maintaining patterns of local diversity.     

Histone 3 modifications and blood pressure in the Beijing Truck Driver Air Pollution Study

Context: Histone modifications regulate gene expression; dysregulation has been linked with cardiovascular diseases. Associations between histone modification levels and blood pressure in humans are unclear.

Objective: We examine the relationship between global histone concentrations and various markers of blood pressure.

Materials and methods: Using the Beijing Truck Driver Air Pollution Study, we investigated global peripheral white blood cell histone modifications (H3K9ac, H3K9me3, H3K27me3, and H3K36me3) associations with pre- and post-work measurements of systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP), and pulse pressure (PP) using multivariable mixed-effect models.

Results: H3K9ac was negatively associated with pre-work SBP and MAP; H3K9me3 was negatively associated with pre-work SBP, DBP, and MAP; and H3K27me3 was negatively associated with pre-work SBP. Among office workers, H3K9me3 was negatively associated with pre-work SBP, DBP, and MAP. Among truck drivers, H3K9ac and H3K27me were negatively associated with pre-work SBP, and H3K27me3 was positively associated with post-work PP.

Discussion and conclusion: Epigenome-wide H3K9ac, H3K9me3, and H3K27me3 were negatively associated with multiple pre-work blood pressure measures. These associations substantially changed during the day, suggesting an influence of daily activities. Blood-based histone modification biomarkers are potential candidates for studies requiring estimations of morning/pre-work blood pressure.