Exploring biomedical ontology mappings with graph theory methods
Background In the era of semantic web, life science ontologies play an important role in tasks such as annotating biological objects, linking relevant data pieces, and verifying data consistency. Understanding ontology structures and overlapping ontologies is essential for tasks such as ontology reuse and development. We present an exploratory study where we examine structure and look for patterns in BioPortal, a comprehensive publicly available repository of live science ontologies. Methods We report an analysis of biomedical ontology mapping data over time. We apply graph theory methods such as Modularity Analysis and Betweenness Centrality to analyse data gathered at five different time points. We identify communities, i.e., sets of overlapping ontologies, and define similar and closest communities. We demonstrate evolution of identified communities over time and identify core ontologies of the closest communities. We use BioPortal project and category data to measure community coherence. We also validate identified communities with their mutual mentions in scientific literature. Results With comparing mapping data gathered at five different time points, we identified similar and closest communities of overlapping ontologies, and demonstrated evolution of communities over time. Results showed that anatomy and health ontologies tend to form more isolated communities compared to other categories. We also showed that communities contain all or the majority of ontologies being used in narrower projects. In addition, we identified major changes in mapping data after migration to BioPortal Version 4.
Kocbek et al. (2017) Exploring biomedical ontology mappings with graph theory methods. PeerJ 5:e2990 https://doi.org/10.7717/peerj.2990
Obesity-induced diet leads to weight gain, systemic metabolic alterations, adipose tissue inflammation, hepatic steatosis, and oxidative stress in gerbils (Meriones unguiculatus)
Background Nowadays, the number of obese people in the world has reached alarming proportions. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. This leads the body to a pro-inflammatory pattern, which may affect the proper functioning of many tissues. Thus, studying the mechanisms by which obesity induces physiological disorders is necessary, and may be facilitated by the use of animal models, in particular rodents. We sought to characterize the metabolic and adipose tissue changes resulting from a diet rich in fats and simple sugars in gerbils. Methods We divided 14 gerbils into two experimental groups that received a diet rich in simple carbohydrates and fats with 5,86 kcal/g (OB, n = 7) or a standard diet with 4.15 kcal/g (CT; n = 7) for 11 weeks. The animals had free access to water and food. The animal weight and food consumption were measured weekly. Blood, adipose tissue and liver of each animal were collected at the end of experiment. The following parameters were determined: cholesterol (COL), triglycerides (TGL) and glycemia (GLI) in the plasma; cytokines (IL-6, IL-10 and TNF-α) and hormones (adiponectin and leptin) in adipose tissue; activity of superoxide dismutase (SOD) and catalase (CAT), extraction and differentiation of fat and histology in liver. Results The consumption of a diet rich in simple carbohydrates and fats led to increased total body weight and increased relative weights of liver and adipose tissue. In addition, we observed increased fasting glucose levels and circulating triglycerides, along with high TNF-α production in adipose tissue and increased total fat, cholesterol and triglyceride contents in the liver, contributing to higher intensity of hepatic steatosis. On the other hand, the animals of this group showed depletion in the enzyme activity of SOD and CAT in the liver, as well as reduction of IL-10 and adiponectin levels in adipose tissue. Discussion High intake of saturated fat and simple carbohydrates establish the gerbil as an experimental model for the study of metabolic and hepatic abnormalities resulting from obesity.
Ventura et al. (2017) Obesity-induced diet leads to weight gain, systemic metabolic alterations, adipose tissue inflammation, hepatic steatosis, and oxidative stress in gerbils (Meriones unguiculatus). PeerJ 5:e2967 https://doi.org/10.7717/peerj.2967
P2X7 antagonism using Brilliant Blue G reduces body weight loss and prolongs survival in female SOD1G93A amyotrophic lateral sclerosis mice
Background Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterised by the accumulation of aggregated proteins, microglia activation and motor neuron loss. The mechanisms underlying neurodegeneration and disease progression in ALS are unknown, but the ATP-gated P2X7 receptor channel is implicated in this disease. Therefore, the current study aimed to examine P2X7 in the context of neurodegeneration, and investigate whether the P2X7 antagonist, Brilliant Blue G (BBG), could alter disease progression in a murine model of ALS. Methods Human SOD1G93A transgenic mice, which normally develop ALS, were injected with BBG or saline, three times per week, from pre-onset of clinical disease (62–64 days of age) until end-stage. During the course of treatment mice were assessed for weight, clinical score and survival, and motor coordination, which was assessed by rotarod performance. Various parameters from end-stage mice were assessed as follows. Motor neuron loss and microgliosis were assessed by immunohistochemistry. Relative amounts of lumbar spinal cord SOD1 and P2X7 were quantified by immunoblotting. Serum monocyte chemoattractant protein-1 was measured by ELISA. Splenic leukocyte populations were assessed by flow cytometry. Relative expression of splenic and hepatic P2X7 mRNA was measured by quantitative real-time PCR. Lumbar spinal cord SOD1 and P2X7 were also quantified by immunoblotting in untreated female SOD1G93A mice during the course of disease. Results BBG treatment reduced body weight loss in SOD1G93A mice of combined sex, but had no effect on clinical score, survival or motor coordination. BBG treatment reduced body weight loss in female, but not male, SOD1G93A mice. BBG treatment also prolonged survival in female, but not male, SOD1G93A mice, extending the mean survival time by 4.3% in female mice compared to female mice treated with saline. BBG treatment had no effect on clinical score or motor coordination in either sex. BBG treatment had no major effect on any end-stage parameters. Total amounts of lumbar spinal cord SOD1 and P2X7 in untreated female SOD1G93A mice did not change over time. Discussion Collectively, this data suggests P2X7 may have a partial role in ALS progression in mice, but additional research is required to fully elucidate the contribution of this receptor in this disease.
Bartlett et al. (2017) P2X7 antagonism using Brilliant Blue G reduces body weight loss and prolongs survival in female SOD1G93A amyotrophic lateral sclerosis mice. PeerJ 5:e3064 https://doi.org/10.7717/peerj.3064
Genetic and structural study of DNA-directed RNA polymerase II of Trypanosoma brucei, towards the designing of novel antiparasitic agents
Trypanosoma brucei brucei (TBB) belongs to the unicellular parasitic protozoa organisms, specifically to the Trypanosoma genus of the Trypanosomatidae class. A variety of different vertebrate species can be infected by TBB, including humans and animals. Under particular conditions, the TBB can be hosted by wild and domestic animals; therefore, an important reservoir of infection always remains available to transmit through tsetse flies. Although the TBB parasite is one of the leading causes of death in the most underdeveloped countries, to date there is neither vaccination available nor any drug against TBB infection. The subunit RPB1 of the TBB DNA-directed RNA polymerase II (DdRpII) constitutes an ideal target for the design of novel inhibitors, since it is instrumental role is vital for the parasite’s survival, proliferation, and transmission. A major goal of the described study is to provide insights for novel anti-TBB agents via a state-of-the-art drug discovery approach of the TBB DdRpII RPB1. In an attempt to understand the function and action mechanisms of this parasite enzyme related to its molecular structure, an in-depth evolutionary study has been conducted in parallel to the in silico molecular designing of the 3D enzyme model, based on state-of-the-art comparative modelling and molecular dynamics techniques. Based on the evolutionary studies results nine new invariant, first-time reported, highly conserved regions have been identified within the DdRpII family enzymes. Consequently, those patches have been examined both at the sequence and structural level and have been evaluated in regard to their pharmacological targeting appropriateness. Finally, the pharmacophore elucidation study enabled us to virtually in silico screen hundreds of compounds and evaluate their interaction capabilities with the enzyme. It was found that a series of chlorine-rich set of compounds were the optimal inhibitors for the TBB DdRpII RPB1 enzyme. All-in-all, herein we present a series of new sites on the TBB DdRpII RPB1 of high pharmacological interest, alongside the construction of the 3D model of the enzyme and the suggestion of a new in silico pharmacophore model for fast screening of potential inhibiting agents.
Papageorgiou et al. (2017) Genetic and structural study of DNA-directed RNA polymerase II of Trypanosoma brucei, towards the designing of novel antiparasitic agents. PeerJ 5:e3061 https://doi.org/10.7717/peerj.3061
A supertree pipeline for summarizing phylogenetic and taxonomic information for millions of species
We present a new supertree method that enables rapid estimation of a summary tree on the scale of millions of leaves. This supertree method summarizes a collection of input phylogenies and an input taxonomy. We introduce formal goals and criteria for such a supertree to satisfy in order to transparently and justifiably represent the input trees. In addition to producing a supertree, our method computes annotations that describe which grouping in the input trees support and conflict with each group in the supertree. We compare our supertree construction method to a previously published supertree construction method by assessing their performance on input trees used to construct the Open Tree of Life version 4, and find that our method increases the number of displayed input splits from 35,518 to 39,639 and decreases the number of conflicting input splits from 2,760 to 1,357. The new supertree method also improves on the previous supertree construction method in that it produces no unsupported branches and avoids unnecessary polytomies. This pipeline is currently used by the Open Tree of Life project to produce all of the versions of project’s “synthetic tree” starting at version 5. This software pipeline is called “propinquity”. It relies heavily on “otcetera”—a set of C++ tools to perform most of the steps of the pipeline. All of the components are free software and are available on GitHub.
Redelings et al. (2017) A supertree pipeline for summarizing phylogenetic and taxonomic information for millions of species. PeerJ 5:e3058 https://doi.org/10.7717/peerj.3058
Specimen-level phylogenetics in paleontology using the Fossilized Birth-Death model with sampled ancestors
Bayesian phylogenetic methods integrating simultaneously morphological and stratigraphic information have been applied increasingly among paleontologists. Most of these studies have used Bayesian methods as an alternative to the widely-used parsimony analysis, to infer macroevolutionary patterns and relationships among species-level or higher taxa. Among recently introduced Bayesian methodologies, the Fossilized Birth-Death (FBD) model allows incorporation of hypotheses on ancestor-descendant relationships in phylogenetic analyses including fossil taxa. Here, the FBD model is used to infer the relationships among an ingroup formed exclusively by fossil individuals, i.e., dipnoan tooth plates from four localities in the Ain el Guettar Formation of Tunisia. Previous analyses of this sample compared the results of phylogenetic analysis using parsimony with stratigraphic methods, inferred a high diversity (five or more genera) in the Ain el Guettar Formation, and interpreted it as an artifact inflated by depositional factors. In the analysis performed here, the uncertainty on the chronostratigraphic relationships among the specimens was included among the prior settings. The results of the analysis confirm the referral of most of the specimens to the taxa Asiatoceratodus, Equinoxiodus, Lavocatodus and Neoceratodus, but reject those to Ceratodus and Ferganoceratodus. The resulting phylogeny constrained the evolution of the Tunisian sample exclusively in the Early Cretaceous, contrasting with the previous scenario inferred by the stratigraphically-calibrated topology resulting from parsimony analysis. The phylogenetic framework also suggests that (1) the sampled localities are laterally equivalent, (2) but three localities are restricted to the youngest part of the section; both results are in agreement with previous stratigraphic analyses of these localities. The FBD model of specimen-level units provides a novel tool for phylogenetic inference among fossils but also for independent tests of stratigraphic scenarios.
Cau (2017) Specimen-level phylogenetics in paleontology using the Fossilized Birth-Death model with sampled ancestors. PeerJ 5:e3055 https://doi.org/10.7717/peerj.3055
Digital reconstruction of the mandible of an adult Lesothosaurus diagnosticus with insight into the tooth replacement process and diet
Fragmentary caudal ends of the left and right mandible assigned to Lesothosaurus diagnosticus, an early ornithischian, was recently discovered in the continental red bed succession of the upper Elliot Formation (Lower Jurassic) at Likhoele Mountain (Mafeteng District) in Lesotho. Using micro-CT scanning, this mandible could be digitally reconstructed in 3D. The replacement teeth within the better preserved (left) dentary were visualised. The computed tomography dataset suggests asynchronous tooth replacement in an individual identified as an adult on the basis of bone histology. Clear evidence for systematic wear facets created by attrition is lacking. The two most heavily worn teeth are only apically truncated. Our observations of this specimen as well as others do not support the high level of dental wear expected from the semi-arid palaeoenvironment in which Lesothosaurus diagnosticus lived. Accordingly, a facultative omnivorous lifestyle, where seasonality determined the availability, quality, and abundance of food is suggested. This would have allowed for adaptability to episodes of increased environmental stress.
Sciscio et al. (2017) Digital reconstruction of the mandible of an adult Lesothosaurus diagnosticus with insight into the tooth replacement process and diet. PeerJ 5:e3054 https://doi.org/10.7717/peerj.3054
The impact of human development on individual health: a causal mediation analysis examining pathways through education and body mass index
Background The macro environment we live in projects what we can achieve and how we behave, and in turn, shapes our health in complex ways. Policymaking will benefit from insights into the mechanisms underlying how national socioeconomic context affects health. This study examined the impact of human development on individual health and the possible mediating roles of education and body mass index (BMI). Methods We analyzed World Health Survey data on 109,448 participants aged 25 or older from 42 low- and middle-income countries with augmented human development index (HDI) in 1990. We used principal components method to create a health score based on measures from eight health state domains, used years of schooling as education indicator and calculated BMI from self-reported height and weight. We used causal mediation analysis technique with random intercepts to account for the multilevel structure. Results Below a reference HDI level of 0.48, HDI was negatively associated with good health (total effect at HDI of 0.23: b = − 3.44, 95% CI [−6.39–−0.49] for males and b = − 5.16, 95% CI [−9.24,–−1.08] for females) but was positively associated with good health above this reference level (total effect at HDI of 0.75: b = 4.16, 95% CI [−0.33–8.66] for males and b = 6.62, 95% CI [0.85–12.38] for females). We found a small positive effect of HDI on health via education across reference HDI levels (b ranging from 0.24 to 0.29 for males and 0.40 to 0.49 for females) but not via pathways involving BMI only. Conclusion Human development has a non-linear effect on individual health, but the impact appears to be mainly through pathways other than education and BMI.
Wang et al. (2017) The impact of human development on individual health: a causal mediation analysis examining pathways through education and body mass index. PeerJ 5:e3053 https://doi.org/10.7717/peerj.3053
Effects of root exudates of woody species on the soil anti-erodibility in the rhizosphere in a karst region, China
Introduction Rhizospheres, the most active interfaces between plants and soils, play a central role in the long-term maintenance of the biosphere. The anti-erodibility of soils (AES) regulated by the root exudates is crucial to the soil stability in the rhizospheres. However, scientists still debate (1) the key organic matter of the root exudates affecting the AES and (2) the interspecific variation of these root exudates. Methods We used an incubation of soils to test the effects of the root exudates from eight woody plant species on the change in soil aggregation and identified the organic matter in these root exudates with gas chromatography-mass spectrometry (GC-MS) and biochemical methods. Furthermore, the relationships between the organic matter in the exudates and the AES in the rhizospheres of 34 additional tree species were analyzed. Results The water-stable aggregates of the soils incubated with the root exudates increased by 15%–50% on average compared with control samples. The interspecific differences were significant. The root exudates included hundreds of specific organic matter types; hydrocarbon, total sugar, total amino acids, and phenolic compounds were crucial to the AES. These organic matter types could explain approximately 20–75% of the variation in the total effect of the root exudates on the AES, which was quantified based on the aggregate status, degree of aggregation, dispersion ratio, and dispersion coefficient. Discussion The effects of the root exudates on the AES and the interspecific variation are as important as that of root density, litters, and vegetation covers. Many studies explored the effects of root density, litters, vegetation covers, and vegetation types on the AES, but little attention has been paid to the effects of the root exudates on the AES. Different plants secrete different relative contents of organic matter resulting in the variation of the effect of the root exudates on the AES. Our study quantified the causal relationships between the root exudates and the AES using modeling experiments in laboratory and field observations and indicated the interspecific variation of the AES and organic matter of the root exudates. Conclusions More organic compounds of the exudates related to the AES were recognized in this study. These results enhance the understanding of the soil stability at a slope and can be applied to ecosystem restoration.
Wang et al. (2017) Effects of root exudates of woody species on the soil anti-erodibility in the rhizosphere in a karst region, China. PeerJ 5:e3029 https://doi.org/10.7717/peerj.3029
Digging deeper: new gene order rearrangements and distinct patterns of codons usage in mitochondrial genomes among shrimps from the Axiidea, Gebiidea and Caridea (Crustacea: Decapoda)
Background Whole mitochondrial DNA is being increasingly utilized for comparative genomic and phylogenetic studies at deep and shallow evolutionary levels for a range of taxonomic groups. Although mitogenome sequences are deposited at an increasing rate into public databases, their taxonomic representation is unequal across major taxonomic groups. In the case of decapod crustaceans, several infraorders, including Axiidea (ghost shrimps, sponge shrimps, and mud lobsters) and Caridea (true shrimps) are still under-represented, limiting comprehensive phylogenetic studies that utilize mitogenomic information. Methods Sequence reads from partial genome scans were generated using the Illumina MiSeq platform and mitogenome sequences were assembled from these low coverage reads. In addition to examining phylogenetic relationships within the three infraorders, Axiidea, Gebiidea, and Caridea, we also investigated the diversity and frequency of codon usage bias and mitogenome gene order rearrangements. Results We present new mitogenome sequences for five shrimp species from Australia that includes two ghost shrimps, Callianassa ceramica and Trypaea australiensis, along with three caridean shrimps, Macrobrachium bullatum, Alpheus lobidens, and Caridina cf. nilotica. Strong differences in codon usage were discovered among the three infraorders and significant gene order rearrangements were observed. While the gene order rearrangements are congruent with the inferred phylogenetic relationships and consistent with taxonomic classification, they are unevenly distributed within and among the three infraorders. Discussion Our findings suggest potential for mitogenome rearrangements to be useful phylogenetic markers for decapod crustaceans and at the same time raise important questions concerning the drivers of mitogenome evolution in different decapod crustacean lineages.
Tan et al. (2017) Digging deeper: new gene order rearrangements and distinct patterns of codons usage in mitochondrial genomes among shrimps from the Axiidea, Gebiidea and Caridea (Crustacea: Decapoda). PeerJ 5:e2982 https://doi.org/10.7717/peerj.2982