RelocaTE2: a high resolution transposable element insertion site mapping tool for population resequencing
Background Transposable element (TE) polymorphisms are important components of population genetic variation. The functional impacts of TEs in gene regulation and generating genetic diversity have been observed in multiple species, but the frequency and magnitude of TE variation is under appreciated. Inexpensive and deep sequencing technology has made it affordable to apply population genetic methods to whole genomes with methods that identify single nucleotide and insertion/deletion polymorphisms. However, identifying TE polymorphisms, particularly transposition events or non-reference insertion sites can be challenging due to the repetitive nature of these sequences, which hamper both the sensitivity and specificity of analysis tools. Methods We have developed the tool RelocaTE2 for identification of TE insertion sites at high sensitivity and specificity. RelocaTE2 searches for known TE sequences in whole genome sequencing reads from second generation sequencing platforms such as Illumina. These sequence reads are used as seeds to pinpoint chromosome locations where TEs have transposed. RelocaTE2 detects target site duplication (TSD) of TE insertions allowing it to report TE polymorphism loci with single base pair precision. Results and Discussion The performance of RelocaTE2 is evaluated using both simulated and real sequence data. RelocaTE2 demonstrate high level of sensitivity and specificity, particularly when the sequence coverage is not shallow. In comparison to other tools tested, RelocaTE2 achieves the best balance between sensitivity and specificity. In particular, RelocaTE2 performs best in prediction of TSDs for TE insertions. Even in highly repetitive regions, such as those tested on rice chromosome 4, RelocaTE2 is able to report up to 95% of simulated TE insertions with less than 0.1% false positive rate using 10-fold genome coverage resequencing data. RelocaTE2 provides a robust solution to identify TE insertion sites and can be incorporated into analysis workflows in support of describing the complete genotype from light coverage genome sequencing.
Chen et al. (2017) RelocaTE2: a high resolution transposable element insertion site mapping tool for population resequencing. PeerJ 5:e2942 https://doi.org/10.7717/peerj.2942
Sequence variability of Chrysanthemum stunt viroid in different chrysanthemum cultivars
Viroids are the smallest infectious agents, and their genomes consist of a short single strand of RNA that does not encode any protein. Chrysanthemum stunt viroid (CSVd), a member of the family Pospiviroidae, causes chrysanthemum stunt disease. Here, we report the genomic variations of CSVd to understand the sequence variability of CSVd in different chrysanthemum cultivars. We randomly sampled 36 different chrysanthemum cultivars and examined the infection of CSVd in each cultivar by reverse transcription polymerase chain reaction (RT-PCR). Eleven cultivars were infected by CSVd. Cloning followed by Sanger sequencing successfully identified a total of 271 CSVd genomes derived from 12 plants from 11 cultivars. They were further classified into 105 CSVd variants. Each single chrysanthemum plant had a different set of CSVd variants. Moreover, different single plants from the same cultivar had different sets of CSVd variants but identical consensus genome sequences. A phylogenetic tree using 12 consensus genome sequences revealed three groups of CSVd genomes, while six different groups were defined by the phylogenetic analysis using 105 variants. Based on the consensus CSVd genome, by combining all variant sequences, we identified 99 single-nucleotide variations (SNVs) as well as three nucleotide positions showing high mutation rates. Although 99 SNVs were identified, most CSVd genomes in this study were derived from variant 1, which is identical to known CSVd SK1 showing pathogenicity.
Choi et al. (2017) Sequence variability of Chrysanthemum stunt viroid in different chrysanthemum cultivars. PeerJ 5:e2933 https://doi.org/10.7717/peerj.2933
Causal events enter awareness faster than non-causal events
Philosophers have long argued that causality cannot be directly observed but requires a conscious inference (Hume, 1967). Albert Michotte however developed numerous visual phenomena in which people seemed to perceive causality akin to primary visual properties like colour or motion (Michotte, 1946). Michotte claimed that the perception of causality did not require a conscious, deliberate inference but, working over 70 years ago, he did not have access to the experimental methods to test this claim. Here we employ Continuous Flash Suppression (CFS)—an interocular suppression technique to render stimuli invisible (Tsuchiya & Koch, 2005)—to test whether causal events enter awareness faster than non-causal events. We presented observers with ‘causal’ and ‘non-causal’ events, and found consistent evidence that participants become aware of causal events more rapidly than non-causal events. Our results suggest that, whilst causality must be inferred from sensory evidence, this inference might be computed at low levels of perceptual processing, and does not depend on a deliberative conscious evaluation of the stimulus. This work therefore supports Michotte’s contention that, like colour or motion, causality is an immediate property of our perception of the world.
Moors et al. (2017) Causal events enter awareness faster than non-causal events. PeerJ 5:e2932 https://doi.org/10.7717/peerj.2932
Floral vasculature and its variation for carpellary supply in Anthurium (Araceae, Alismatales)
Introduction and Aims Anthurium is the largest genus of Araceae, with 950 species distributed in the neotropics. Despite the great diversity of the genus, the knowledge of its floral vasculature is based on observations in only two species, viz. A. denudatum and A. lhotzkyanum, with remarkable variation in vascular carpellary supply: carpels are either vascularized by ventral bundles alone or by reduced dorsal bundles in addition to the ventral ones. Our main objective is to test this peculiar variation through a detailed anatomical study of the floral vasculature in taxa belonging to some sections of Anthurium designated as monophyletic groups in recent phylogenies. Methods We compare the floral vasculature of 20 neotropical species belonging to distinct sections of Anthurium, using both light and confocal laser scanning microscopies. Results The number and position of vascular bundles are constant within the tepals and stamens, regardless of the species and sections studied. However, the gynoecium vasculature exhibits variation between species belonging to the same or different sections. Our results reveal two patterns of vasculature: carpels vascularized by synlateral bundles alone (Pattern A) and carpels vascularized by both dorsal and synlateral bundles (Pattern B). Pattern A is shared by the majority of species studied here and corroborates the previous data in the literature. Pattern B occurs in three species: A. affine (Anthurium sect. Pachyneurium series Pachyneurium), A. obtusum and A. scandens (Anthurium sect. Tetraspermium), described here for the first time for the genus. Conclusions The variation in the supply to the carpels in Anthurium is corroborated here. However, our results in addition to those from the available literature suggest the existence of three patterns (A, B and C) of carpellary vasculature. Based on the recent phylogeny of Anthurium it is possible to notice that the three patterns of carpellary vasculature occur in representatives of Clade B and deserve to be investigated in a larger number of species. Pattern A could be a plesiomorphy for the genus and the occurrence of dorsal bundles could be a derived character. Our data contributes to the taxonomy and to the understanding of the floral evolution of the largest neotropical genus of Araceae.
Poli et al. (2017) Floral vasculature and its variation for carpellary supply in Anthurium (Araceae, Alismatales). PeerJ 5:e2929 https://doi.org/10.7717/peerj.2929
Evolution of gremlin 2 in cetartiodactyl mammals: gene loss coincides with lack of upper jaw incisors in ruminants
Understanding the processes that give rise to genomic variability in extant species is an active area of research within evolutionary biology. With the availability of whole genome sequences, it is possible to quantify different forms of variability such as variation in gene copy number, which has been described as an important source of genetic variability and in consequence of phenotypic variability. Most of the research on this topic has been focused on understanding the biological significance of gene duplication, and less attention has been given to the evolutionary role of gene loss. Gremlin 2 is a member of the DAN gene family and plays a significant role in tooth development by blocking the ligand-signaling pathway of BMP2 and BMP4. The goal of this study was to investigate the evolutionary history of gremlin 2 in cetartiodactyl mammals, a group that possesses highly divergent teeth morphology. Results from our analyses indicate that gremlin 2 has experienced a mixture of gene loss, gene duplication, and rate acceleration. Although the last common ancestor of cetartiodactyls possessed a single gene copy, pigs and camels are the only cetartiodactyl groups that have retained gremlin 2. According to the phyletic distribution of this gene and synteny analyses, we propose that gremlin 2 was lost in the common ancestor of ruminants and cetaceans between 56.3 and 63.5 million years ago as a product of a chromosomal rearrangement. Our analyses also indicate that the rate of evolution of gremlin 2 has been accelerated in the two groups that have retained this gene. Additionally, the lack of this gene could explain the high diversity of teeth among cetartiodactyl mammals; specifically, the presence of this gene could act as a biological constraint. Thus, our results support the notions that gene loss is a way to increase phenotypic diversity and that gremlin 2 is a dispensable gene, at least in cetartiodactyl mammals.
Opazo et al. (2017) Evolution of gremlin 2 in cetartiodactyl mammals: gene loss coincides with lack of upper jaw incisors in ruminants. PeerJ 5:e2901 https://doi.org/10.7717/peerj.2901
Genomic insight into pathogenicity of dematiaceous fungus Corynespora cassiicola
Corynespora cassiicola is a common plant pathogen that causes leaf spot disease in a broad range of crop, and it heavily affect rubber trees in Malaysia (Hsueh, 2011; Nghia et al., 2008). The isolation of UM 591 from a patient’s contact lens indicates the pathogenic potential of this dematiaceous fungus in human. However, the underlying factors that contribute to the opportunistic cross-infection have not been fully studied. We employed genome sequencing and gene homology annotations in attempt to identify these factors in UM 591 using data obtained from publicly available bioinformatics databases. The assembly size of UM 591 genome is 41.8 Mbp, and a total of 13,531 (≥99 bp) genes have been predicted. UM 591 is enriched with genes that encode for glycoside hydrolases, carbohydrate esterases, auxiliary activity enzymes and cell wall degrading enzymes. Virulent genes comprising of CAZymes, peptidases, and hypervirulence-associated cutinases were found to be present in the fungal genome. Comparative analysis result shows that UM 591 possesses higher number of carbohydrate esterases family 10 (CE10) CAZymes compared to other species of fungi in this study, and these enzymes hydrolyses wide range of carbohydrate and non-carbohydrate substrates. Putative melanin, siderophore, ent-kaurene, and lycopene biosynthesis gene clusters are predicted, and these gene clusters denote that UM 591 are capable of protecting itself from the UV and chemical stresses, allowing it to adapt to different environment. Putative sterigmatocystin, HC-toxin, cercosporin, and gliotoxin biosynthesis gene cluster are predicted. This finding have highlighted the necrotrophic and invasive nature of UM 591.
Looi et al. (2017) Genomic insight into pathogenicity of dematiaceous fungus Corynespora cassiicola. PeerJ 5:e2841 https://doi.org/10.7717/peerj.2841
Computer simulation of Cerebral Arteriovenous Malformation—Validation analysis of hemodynamics parameters
Problem The purpose of this work is to provide some validation methods for evaluating the hemodynamic assessment of Cerebral Arteriovenous Malformation (CAVM). This article emphasizes the importance of validating noninvasive measurements for CAVM patients, which are designed using lumped models for complex vessel structure. Methods The validation of the hemodynamics assessment is based on invasive clinical measurements and cross-validation techniques with the Philips proprietary validated software’s Qflow and 2D Perfursion. Results The modeling results are validated for 30 CAVM patients for 150 vessel locations. Mean flow, diameter, and pressure were compared between modeling results and with clinical/cross validation measurements, using an independent two-tailed Student t test. Exponential regression analysis was used to assess the relationship between blood flow, vessel diameter, and pressure between them. Univariate analysis is used to assess the relationship between vessel diameter, vessel cross-sectional area, AVM volume, AVM pressure, and AVM flow results were performed with linear or exponential regression. Discussion Modeling results were compared with clinical measurements from vessel locations of cerebral regions. Also, the model is cross validated with Philips proprietary validated software’s Qflow and 2D Perfursion. Our results shows that modeling results and clinical results are nearly matching with a small deviation. Conclusion In this article, we have validated our modeling results with clinical measurements. The new approach for cross-validation is proposed by demonstrating the accuracy of our results with a validated product in a clinical environment.
Kumar et al. (2017) Computer simulation of Cerebral Arteriovenous Malformation—Validation analysis of hemodynamics parameters. PeerJ 5:e2724 https://doi.org/10.7717/peerj.2724
The use of gene interaction networks to improve the identification of cancer driver genes
Bioinformaticians have implemented different strategies to distinguish cancer driver genes from passenger genes. One of the more recent advances uses a pathway-oriented approach. Methods that employ this strategy are highly dependent on the quality and size of the pathway interaction network employed, and require a powerful statistical environment for analyses. A number of genomic libraries are available in R. DriverNet and DawnRank employ pathway-based methods that use gene interaction graphs in matrix form. We investigated the benefit of combining data from 3 different sources on the prediction outcome of cancer driver genes by DriverNet and DawnRank. An enriched dataset was derived comprising 13,862 genes with 372,250 interactions, which increased its accuracy by 17% and 28%, respectively, compared to their original networks. The study identified 33 new candidate driver genes. Our study highlights the potential of combining networks and weighting edges to provide greater accuracy in the identification of cancer driver genes.
Ramsahai et al. (2017) The use of gene interaction networks to improve the identification of cancer driver genes. PeerJ 5:e2568 https://doi.org/10.7717/peerj.2568
Retrospective study of prognostic factors in pediatric invasive pneumococcal disease
Streptococcus pneumoniae remains the leading causative pathogen in pediatric pneumonia and bacteremia throughout the world. The invasive pneumococcal disease (IPD) is known as isolation of S. pneumoniae from a normally sterile site (e.g., blood, cerebrospinal fluid, synovial fluid, pericardial fluid, pleural fluid, or peritoneal fluid). The aim of this study is to survey the clinical manifestations and laboratory results of IPD and identify the prognostic factors of mortality. From January 2001 to December 2006, a retrospective review of chart was performed in a teaching hospital in Taipei. The hospitalized pediatric patients with the diagnosis of pneumonia, arthritis, infectious endocarditis, meningitis or sepsis were recruited. Among them, 50 patients were pneumococcal infections proved by positive culture results or antigen tests. Clinical manifestations, laboratory data and hospitalization courses were analyzed. The median age was 3.5-year-old and there were 30 male patients (60%). Eight patients (16%) had underlying disease such as leukemia or congenital heart disease. Hemolytic uremic syndrome (HUS) was observed in ten patients and extracorporeal membrane oxygenation (ECMO) was performed in three patients. Leukocytosis, elevated C-reactive protein and AST level were noted in most of the patients. The overall mortality rate was 10%. We found that leukopenia, thrombocytopenia and high CRP level were significant predictors for mortality. In conclusion, S. pneumoniae remains an important health threat worldwide and IPD is life-threatening with high mortality rate. We found leukopenia, thrombocytopenia, and high CRP levels to be associated with mortality in pediatric IPD, and these factors are worthy of special attention at admission. Although we failed to identify a statistically significant prognostic factor in multivariate analysis due to relatively small sample size, we suggest an aggressive antibiotic treatment in patients with these factors at admission. Further large-scale studies are warranted.
Chiu et al. (2017) Retrospective study of prognostic factors in pediatric invasive pneumococcal disease. PeerJ 5:e2941 https://doi.org/10.7717/peerj.2941
Antibiotic resistance potential of the healthy preterm infant gut microbiome
Background Few studies have investigated the gut microbiome of infants, fewer still preterm infants. In this study we sought to quantify and interrogate the resistome within a cohort of premature infants using shotgun metagenomic sequencing. We describe the gut microbiomes from preterm but healthy infants, characterising the taxonomic diversity identified and frequency of antibiotic resistance genes detected. Results Dominant clinically important species identified within the microbiomes included C. perfringens, K. pneumoniae and members of the Staphylococci and Enterobacter genera. Screening at the gene level we identified an average of 13 antimicrobial resistance genes per preterm infant, ranging across eight different antibiotic classes, including aminoglycosides and fluoroquinolones. Some antibiotic resistance genes were associated with clinically relevant bacteria, including the identification of mecA and high levels of Staphylococci within some infants. We were able to demonstrate that in a third of the infants the S. aureus identified was unrelated using MLST or metagenome assembly, but low abundance prevented such analysis within the remaining samples. Conclusions We found that the healthy preterm infant gut microbiomes in this study harboured a significant diversity of antibiotic resistance genes. This broad picture of resistances and the wider taxonomic diversity identified raises further caution to the use of antibiotics without consideration of the resident microbial communities.
Rose et al. (2017) Antibiotic resistance potential of the healthy preterm infant gut microbiome. PeerJ 5:e2928 https://doi.org/10.7717/peerj.2928