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141.

Background

Due to the rapidly expanding body of biomedical literature, biologists require increasingly sophisticated and efficient systems to help them to search for relevant information. Such systems should account for the multiple written variants used to represent biomedical concepts, and allow the user to search for specific pieces of knowledge (or events) involving these concepts, e.g., protein-protein interactions. Such functionality requires access to detailed information about words used in the biomedical literature. Existing databases and ontologies often have a specific focus and are oriented towards human use. Consequently, biological knowledge is dispersed amongst many resources, which often do not attempt to account for the large and frequently changing set of variants that appear in the literature. Additionally, such resources typically do not provide information about how terms relate to each other in texts to describe events.

Results

This article provides an overview of the design, construction and evaluation of a large-scale lexical and conceptual resource for the biomedical domain, the BioLexicon. The resource can be exploited by text mining tools at several levels, e.g., part-of-speech tagging, recognition of biomedical entities, and the extraction of events in which they are involved. As such, the BioLexicon must account for real usage of words in biomedical texts. In particular, the BioLexicon gathers together different types of terms from several existing data resources into a single, unified repository, and augments them with new term variants automatically extracted from biomedical literature. Extraction of events is facilitated through the inclusion of biologically pertinent verbs (around which events are typically organized) together with information about typical patterns of grammatical and semantic behaviour, which are acquired from domain-specific texts. In order to foster interoperability, the BioLexicon is modelled using the Lexical Markup Framework, an ISO standard.

Conclusions

The BioLexicon contains over 2.2 M lexical entries and over 1.8 M terminological variants, as well as over 3.3 M semantic relations, including over 2 M synonymy relations. Its exploitation can benefit both application developers and users. We demonstrate some such benefits by describing integration of the resource into a number of different tools, and evaluating improvements in performance that this can bring.  相似文献   
142.
To assess the usefulness and applications of machine vision (MV) and machine learning (ML) techniques that have been used to develop a single cell-based phenotypic (live and fixed biomarkers) platform that correlates with tumor biological aggressiveness and risk stratification, 100 fresh prostate samples were acquired, and areas of prostate cancer were determined by post-surgery pathology reports logged by an independent pathologist. The prostate samples were dissociated into single-cell suspensions in the presence of an extracellular matrix formulation. These samples were analyzed via live-cell microscopy. Dynamic and fixed phenotypic biomarkers per cell were quantified using objective MV software and ML algorithms. The predictive nature of the ML algorithms was developed in two stages. First, random forest (RF) algorithms were developed using 70% of the samples. The developed algorithms were then tested for their predictive performance using the blinded test dataset that contained 30% of the samples in the second stage. Based on the ROC (receiver operating characteristic) curve analysis, thresholds were set to maximize both sensitivity and specificity. We determined the sensitivity and specificity of the assay by comparing the algorithm-generated predictions with adverse pathologic features in the radical prostatectomy (RP) specimens. Using MV and ML algorithms, the biomarkers predictive of adverse pathology at RP were ranked and a prostate cancer patient risk stratification test was developed that distinguishes patients based on surgical adverse pathology features. The ability to identify and track large numbers of individual cells over the length of the microscopy experimental monitoring cycles, in an automated way, created a large biomarker dataset of primary biomarkers. This biomarker dataset was then interrogated with ML algorithms used to correlate with post-surgical adverse pathology findings. Algorithms were generated that predicted adverse pathology with >0.85 sensitivity and specificity and an AUC (area under the curve) of >0.85. Phenotypic biomarkers provide cellular and molecular details that are informative for predicting post-surgical adverse pathologies when considering tumor biopsy samples. Artificial intelligence ML-based approaches for cancer risk stratification are emerging as important and powerful tools to compliment current measures of risk stratification. These techniques have capabilities to address tumor heterogeneity and the molecular complexity of prostate cancer. Specifically, the phenotypic test is a novel example of leveraging biomarkers and advances in MV and ML for developing a powerful prognostic and risk-stratification tool for prostate cancer patients.  相似文献   
143.
The analysis of less common variants in genome-wide association studies promises to elucidate complex trait genetics but is hampered by low power to reliably detect association. We show that addition of population-specific exome sequence data to global reference data allows more accurate imputation, particularly of less common SNPs (minor allele frequency 1–10%) in two very different European populations. The imputation improvement corresponds to an increase in effective sample size of 28–38%, for SNPs with a minor allele frequency in the range 1–3%.  相似文献   
144.
The isolated ecosystem of Rubondo Island National Park, Tanzania is an interesting model site, inhabited by an assembly of primate species with various histories: two introduced primate species, Pantroglodytes (chimpanzee) and Colobusguereza (colobus), and a single indigenous species Chlorocebusaethiopspygerythrus (vervet monkey). Apart from important lessons for future introduction/re-introduction projects, Rubondo National Park offers a unique place to study the patterns of transmission of primate parasites and their host specificity. Blastocystis was detected using standard microscopy, together with PCR-based determination and the prevalence and subtype identification of Blastocystis was determined in each primate species. Subtype (ST) 1 was detected in all three Rubondo primate populations; ST2, ST3 and ST5 were found in colobus and vervet monkeys. All chimpanzee isolates of Blastocystis belonged exclusively to ST1, which formed a discrete group, suggesting that Rubondo chimpanzees are colonized by a single, host-specific Blastocystis strain that circulates among the members of the group. Phylogenetic analysis indicated that transmission of Blastocystis did not occur between Rubondo primate populations. Observed host specificity of Blastocystis provides a new understanding of the transmission and distribution of Blastocystis among sympatric hosts under natural conditions.  相似文献   
145.
Brain, liver, kidney, heart, and skeletal muscle from fatty liver dystrophy (fld/fld) mice, which do not express lipin 1 (lipin), contained much less Mg(2+)-dependent phosphatidic acid phosphatase (PAP) activity than tissues from wild type mice. Lipin harboring the fld(2j) (Gly(84) --> Arg) mutation exhibited relatively little PAP activity. These results indicate that lipin is a major PAP in vivo and that the loss of PAP activity contributes to the fld phenotype. PAP activity was readily detected in immune complexes of lipin from 3T3-L1 adipocytes, where the protein was found both as a microsomal form and a soluble, more highly phosphorylated, form. Fifteen phosphorylation sites were identified by mass spectrometric analyses. Insulin increased the phosphorylation of multiple sites and promoted a gel shift that was due in part to phosphorylation of Ser(106). In contrast, epinephrine and oleic acid promoted dephosphorylation of lipin. The PAP-specific activity of lipin was not affected by the hormones or by dephosphorylation of lipin with protein phosphatase 1. However, the ratio of soluble to microsomal lipin was markedly increased in response to insulin and decreased in response to epinephrine and oleic acid. The results suggest that insulin and epinephrine control lipin primarily by changing localization rather than intrinsic PAP activity.  相似文献   
146.
Identifying the sources of behavioral diversity in non-human primates is vital to understanding the evolution of human behavior. Stone handling (SH, hereafter) is a form of object play consisting of the manipulation of stones by performing various behavioral patterns. This behavior is socially transmitted from generation to generation in Japanese macaques (Macaca fuscata), as a behavioral tradition. SH behavior in particular may reflect on the origin and evolution of stone-tool material culture. The objective of this study was to assess how group size, age structure, and age- and sex-related differences may account for the substantial intra- and inter-troop variations in SH reported in ten troops of Japanese macaques. Our results supported the hypothesis that patterns of variation in SH across troops reflected variability in group size and composition in age classes. We found that troop size was correlated with the proportion of troop members exhibiting SH simultaneously. The effect of troop size on the synchronized performance of SH may reveal the contagious nature of play. Our results suggest that the age structure of the group may affect the diffusion of SH. As predicted by the surplus energy hypothesis, a major functional hypothesis about play, intra-group variation in SH reflected more age- than sex-related differences. SH mainly occurred and was more frequent in younger than in older individuals, whereas no significant sex differences were found. SH episodes were shorter, more vigorous, and SH patterns were more diverse and less complex in immature than in mature individuals. The present findings reveal that age-related factors and group size may constrain the performance, diffusion, and maintenance of SH within a troop. Contrary to most other socially transmitted stone-tool using behaviors in non-human primates and early hominids, there is no optimal SH pattern. Provided some form of social learning, the non-adaptive nature of SH may allow particular SH pattern preferences to emerge at the group level. Our findings urge the use of an inter-populational comparative approach based on multivariate analyses when addressing the question of the evolution of behavioral traditions in primate and human populations.  相似文献   
147.
148.

The callitrichids are non-human primates that feed on insects and plant matter in nature, but in captivity, they are fed mostly an artificial diet containing amounts of gluten, in their toxic forms in items such as wheat, barley and rye. The aim of this research was to estimate the blood β-defensin and Toll like receptor 5 (TLR5) gene expressions and to analyze the stool consistency (firm, soft, diarrheic) in Leontocebus fuscicollis raised in captivity. Blood samples of animals under gluten-free and gluten diets were collected and their fecal output quality was periodically monitored and classified during the course of the study. Gene expression was evaluated using real-time PCR. The stool consistencies of individuals fed a gluten diet were most frequently soft or diarrheic, while it was mostly normal in individuals fed a gluten-free diet. β-Defensin expression increased in individuals fed a gluten diet, but decreased after 15 days. Expression normalized between 30 and 45 days on a gluten-free diet. However, expression of the TLR5 gene did not change under a gluten diet. A gluten diet affects stool quality, and brings about an immediate increase in blood β-defensin expression in the beginning but decreases after 15 days.

  相似文献   
149.
150.
Following the bite of an infective mosquito, malaria parasites first invade the liver where they develop and replicate for a number of days before being released into the bloodstream where they invade red blood cells and cause disease. The biology of the liver stages of malaria parasites is relatively poorly understood due to the inaccessibility of the parasites to sampling during this phase of their life cycle. Here we report the detection in blood and faecal samples of malaria parasite DNA throughout their development in the livers of mice and before the parasites begin their growth in the blood circulation. It is shown that parasite DNA derived from pre-erythrocytic stage parasites reaches the faeces via the bile. We then show that different primate malaria species can be detected by PCR in blood and faecal samples from naturally infected captive macaque monkeys. These results demonstrate that pre-erythrocytic parasites can be detected and quantified in experimentally infected animals. Furthermore, these results have important implications for both molecular epidemiology and phylogenetics of malaria parasites. In the former case, individuals who are malaria parasite negative by microscopy, but PCR positive for parasite DNA in their blood, are considered to be “sub-microscopic” blood stage parasite carriers. We now propose that PCR positivity is not necessarily an indicator of the presence of blood stage parasites, as the DNA could derive from pre-erythrocytic parasites. Similarly, in the case of molecular phylogenetics based on DNA sequences alone, we argue that DNA amplified from blood or faeces does not necessarily come from a parasite species that infects the red blood cells of that particular host.  相似文献   
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