Rule extraction in gene–disease relationship discovery

Background

Biomedical data available to researchers and clinicians have increased dramatically over the past years because of the exponential growth of knowledge in medical biology. It is difficult for curators to go through all of the unstructured documents so as to curate the information to the database. Associating genes with diseases is important because it is a fundamental challenge in human health with applications to understanding disease properties and developing new techniques for prevention, diagnosis and therapy.

Methods

Our study uses the automatic rule-learning approach to gene–disease relationship extraction. We first prepare the experimental corpus from MEDLINE and OMIM. A parser is applied to produce some grammatical information. We then learn all possible rules that discriminate relevant from irrelevant sentences. After that, we compute the scores of the learned rules in order to select rules of interest. As a result, a set of rules is generated.

Results

We produce the learned rules automatically from the 1000 positive and 1000 negative sentences. The test set includes 400 sentences composed of 200 positives and 200 negatives. Precision, recall and F-score served as our evaluation metrics. The results reveal that the maximal precision rate is 77.8% and the maximal recall rate is 63.5%. The maximal F-score is 66.9% where the precision rate is 70.6% and the recall rate is 63.5%.

Conclusions

We employ the rule-learning approach to extract gene–disease relationships. Our main contributions are to build rules automatically and to support a more complete set of rules than a manually generated one. The experiments show exhilarating results and some improving efforts will be made in the future.     

Differences in circadian patterns between rural and urban populations: An epidemiological study in countryside

The physiological pattern of the sleep–wake cycle is influenced by external synchronizing agents such as light and social patterns, creating variations in each individual’s preferred active and sleep periods. Because of the demands of a 24-h working society, it may be imperative for many people to adapt their sleep patterns (physiologically) to their daily activities. Therefore, we analyzed the difference in sleep patterns and chronobiological parameters between an essentially rural farming and urban small-town populations. We studied 5942 subjects (women, 67.1%, N?=?3985; mean age, 44.3?±?13.1 years), from which the chronotype, circadian sleep pattern, and period of light exposure were collected using the Munich Chronotype Questionnaire (MCTQ). A structured questionnaire was also made for collection of social and demographic information. Compared with the urban population (N?=?3427, 57.7%), the rural population (N?=?2515, 42.3%) presented a more predominantly early sleep pattern, as determined by the mid-sleep phase (rural: 2.26?±?1.16; urban: 3.15?±?1.55; t-test, p?<?0.001). We also found less social jetlag (rural: 0.32; urban: 0.55; Mann–Whitney U test, p?<?0.001) and higher light-exposure (rural: 9.55?±?2.31; urban: 8.46?±?2.85; t test, p?<?0.001) in the rural population. Additionally, the rural population presented a higher prevalence of psychiatric disorders (rural: 156, 6.20%; urban: 165, 4.80%; Chi-square, p?<?0.05), and a lower prevalence of metabolic diseases (rural: 143, 5.70%; urban: 225, 6.60%; Chi-square, p?<?0.05). The significant difference in sleep parameters, chronotype, and light exposure between groups remained after multivariate regression analysis (r^2?=?0.41, F?=?297.19, p?<?0.001, β?=?1.208). In this study, there was a significant difference between the rural and urban populations in natural light exposure and sleeping patterns. Because of agricultural work schedules, rural populations spend considerable time outside that is an obligation related to work schedules. Our results emphasize the idea that latitude may not be the main factor influencing individual circadian habits. Rather, circadian physiology adapts to differences in exposure to light (natural and artificial) as well as social and work schedules.     

Liquid chromatography tandem mass spectrometry in study of the pharmacokinetics of six steroidal saponins in rats

A rapid, simple and sensitive high-performance liquid chromatography tandem mass spectrometry method was developed and validated for simultaneous determination of six main steroidal saponins in Paris polyphylla in rat plasma. Ginsenoside Rg3 was selected as the internal standard (IS). Plasma samples were pretreated with protein precipitation, and the separation was achieved on a reverse phase Agilent poroshell120 EC-C18 column using a gradient mobile phase system of acetonitrile–water containing 0.1% formic acid. The triple quadruple mass spectrometer was set in negative electrospray ionization mode and multiple reaction monitoring (MRM) was used for six steroidal saponins quantification. The precursors to produce ion transitions monitored for polyphyllin I, polyphyllin II, polyphyllin VI, polyphyllin VII, dioscin, gracillin and IS were m/z 899.5 > 853.4, 1059.5 > 1013.5, 783.4 > 737.4, 1075.5 > 1029.5, 913.5 > 867.4, 929.5 > 883.4 and 819.5 > 783.4, respectively. The intra- and inter-day precisions (RSD%) were less than 13% and the average extraction recoveries ranged from 85% to 97.0% for each analyte. Six steroidal saponins were proved to be stable during sample storage, preparation and analytical procedures. The established method was employed for simultaneous quantification and successfully used for the first time for the pharmacokinetics evaluation of the six main compounds after intragastric administration of P. polyphylla extract in Sprague–Dawley rats.     

Segregation in the African wintering ranges of English and Swiss Swallow Hirundo rustica populations: a stable isotope study

Capsule Stable isotope analysis of Swallow feathers, grown in Africa, revealed significant differences between populations breeding in Switzerland and England.

Aims To investigate the extent to which Swallow populations breeding in Switzerland and England are separated on their African wintering grounds.

Methods Swallows were caught at breeding colonies, biometric measurements were taken and feathers, grown in Africa, were collected. Feathers were combusted in a Carlo Erba C/N/S analyser and the δ¹³C and δ¹⁵N signatures were measured using a mass spectrometer.

Results The δ¹³C signatures of Swiss birds were significantly more depleted than those of birds from England. The δ¹⁵N signatures did not differ between the two populations.

Conclusion Birds from Switzerland and England probably winter in geographically distinct parts of Africa. The Swiss birds probably feed on prey that are more reliant on C₃ vegetation, from woodlands, than the prey of English birds, which are more reliant on C₄ vegetation, from grasslands.     

Genotype Imputation Reference Panel Selection Using Maximal Phylogenetic Diversity

The recent dramatic cost reduction of next-generation sequencing technology enables investigators to assess most variants in the human genome to identify risk variants for complex diseases. However, sequencing large samples remains very expensive. For a study sample with existing genotype data, such as array data from genome-wide association studies, a cost-effective approach is to sequence a subset of the study sample and then to impute the rest of the study sample, using the sequenced subset as a reference panel. The use of such an internal reference panel identifies population-specific variants and avoids the problem of a substantial mismatch in ancestry background between the study population and the reference population. To efficiently select an internal panel, we introduce an idea of phylogenetic diversity from mathematical phylogenetics and comparative genomics. We propose the “most diverse reference panel”, defined as the subset with the maximal “phylogenetic diversity”, thereby incorporating individuals that span a diverse range of genotypes within the sample. Using data both from simulations and from the 1000 Genomes Project, we show that the most diverse reference panel can substantially improve the imputation accuracy compared to randomly selected reference panels, especially for the imputation of rare variants. The improvement in imputation accuracy holds across different marker densities, reference panel sizes, and lengths for the imputed segments. We thus propose a novel strategy for planning sequencing studies on samples with existing genotype data.     

Discovery of highly potent and selective D4 ligands by interactive SAR study

A series of thienylmethylphenylpiperazins was synthesized and tested for affinity towards the five subtypes of dopaminergic receptors. Compound 5f showed more than 1000 folds selectivity to D4 receptors; analogue 5e showed the highest affinity to D4 receptors with K_i 3.9 nM. An interactive SAR approach was adopted and lead to compound 14a with K_i (D4) as low as 0.03 nM. Molecular docking studies showed a potential, first to report arene cation interaction between the D4 unique residue Arg-186 and the ligands’ arene moiety, explaining the importance of having a strong negative electrostatic potential at this area of the compound structure.     

On the concept and elucidation of endogenous retroviruses

Endogenous retrovirus (ERV) genomes integrated into the chromosomal DNA of the host were first detected in chickens and mice as Mendelian determinants of Gag and Env proteins and of the release of infectious virus particles. The presence of ERV was confirmed by DNA hybridization. With complete host genomes available for analysis, we can now see the great extent of viral invasion into the genomes of numerous vertebrate species, including humans. ERVs are found at many loci in host DNA and also in the genomes of large DNA viruses, such as herpesviruses and poxviruses. The evolution of xenotropism and cross-species infection is discussed in the light of the dynamic relationship between exogenous and endogenous retroviruses.     

Inheritance patterns of ITS1, chloroplasts and mitochondria in artificial hybrids of the seaweeds Fucus serratus and F. evanescens (Phaeophyceae)

Patterns of nuclear and organelle inheritance among artificial hybrids of the seaweeds Fucus serratus and F. evanescens were detected using single-strand conformation polymorphism (SSCP). Three alleles were identified in the 231?bp rDNA-ITS1 gene (nuclear): two in F. serratus and one in F. evanescens. Alleles differed by 1–2?bp and all hybrids possessed one allele from each parent. Two haplotypes were present in the 288?bp Rubisco spacer (chloroplast), differentiated by a 33?bp indel. Two haplotypes differing by a single nucleotide were found in a 135?bp region of nad11 gene (mitochondrion). Both organelles are maternally inherited, as all hybrids contained the haplotypes of the parent contributing the egg. Although laboratory hybrids among Fucus spp. have been produced previously, this is the first time that both nuclear and cytoplasmic genetic markers have been used to document inheritance patterns. SSCPs analysed on an automated sequencer offer a rapid and powerful approach for identifying suspected hybrids from field samples, as well as a screen for intraspecific and intra-individual variation in DNA regions prior to confirmation of variations by sequencing.     

Some New Aryl-5′-fluoro-2′-meth-oxyphenyl Ketones and Their Thiosemicarbazones as Possible Fungicides

Feeding studies on rice genetically modified with soybean glycinin were performed on rats for four weeks. The rats were divided into three groups, each being fed on (I) only a commercial diet, (II) this diet plus control rice and (III) this diet plus rice genetically modified with glycinin. The rats were fed with 10 g/kg-weight of rice every day by oral administration. During the test period, the rats in every group grew well without marked differences in appearance, food intake, body weight, or cumulative body weight gain. There were also no significant differences in the blood count, blood composition or internal organ weights among the rats. Necropsy at the end of the experiment indicated neither pathological symptoms nor histopathological abnormalities in the liver and kidney. Judging from these results, the rice genetically modified with glycinin is considered to have been essentially the same in nutritional and biochemical characteristics as the control rice.