The large amount of repeats, especially high copy repeats, in the genomes of higher animals and plants makes whole genome assembly (WGA) quite difficult. In order to solve this problem, we tried to identify repeats and mask them prior to assembly even at the stage of genome survey. It is known that repeats of different copy number have different probabilities of appearance in shotgun data, so based on this principle, we constructed a statistical model and inferred criteria for mathematically defined repeats (MDRs) at different shotgun coverages. According to these criteria, we developed software MDRmasker to identify and mask MDRs in shotgun data. With repeats masked prior to assembly, the speed of assembly was increased with lower error probability. In addition, clone-insert size affect the accuracy of repeat assembly and scaffold construction, we also designed length distribution of clone-inserts using our model. In our simulated genomes of human and rice, the length distribution of repeats is different, so their optimal length distributions of clone-inserts were not the same. Thus with optimal length distribution of clone-inserts, a given genome could be assembled better at lower coverage.
Animals ; Cloning, Molecular ; Genome ; Genome, Human ; Genomics ; methods ; Humans ; Models, Genetic ; Models, Statistical ; Models, Theoretical ; Oryza ; genetics ; Sequence Analysis, DNA

OBJECTIVETo introduce the application of Multifactor Dimensionality Reduction (MDR) method for detecting gene-gene interactions in genetic case-control studies.

METHODSA brief overview on basic steps involved in the implementation, theoretical details, available software as well as the use and features of the MDR method were discussed based on a practical research case.

RESULTSAdvantages of MDR were compared to the conventional statistical approaches, showing that MDR method was a novel, nonparametric, genetic model-free approach that was developed specifically for detecting gene-gene interactions. Theoretical and empirical studies suggested that MDR was having reasonable power for detecting gene-gene interactions. Applications of MDR method had found the evidence of gene-gene interactions in several diseases such as sporadic breast cancer, atrial fibrillation and essential hypertension.

CONCLUSIONMDR method could be used for detecting gene-gene interactions in genetic case-control studies as having great advantages versus the conventional statistical approaches.

This article review the application of chi-square test of various data handling methods and exact test in Hardy-Weinberg equilibrium testing of human genetic marker in population genetics. The importance of HWE-exact test in multiallelic system was emphasized, especially in the study of forensic VNTR and STR typing.
Alleles ; Chi-Square Distribution ; Forensic Medicine ; Gene Frequency ; Genetics, Population/methods* ; Genotype ; Humans ; Likelihood Functions ; Models, Genetic ; Models, Statistical

In order to overcome the effects of the anti-aliasing filter and the colored background noise, an adaptive algorithm is proposed to estimate the parameters of ion channel kinetics and the background noise, and whereafter the ion channel signal could be restored from the strong noisy patch-clamp recordings. The algorithm cross-couples the recursive expectation-maximization algorithm, which estimates optimally the parameters of hidden Markov model, and the recursive extended least square algorithm, which estimates optimally the characteristics of the background noise. Simulation suggests that this cross-coupling algorithm convergences consistently, and is very robust to the inexact conformation number.
Algorithms ; Ion Channels ; physiology ; Least-Squares Analysis ; Likelihood Functions ; Models, Theoretical ; Noise ; Patch-Clamp Techniques ; methods ; Signal Processing, Computer-Assisted

WOMBAT is a software package for quantitative genetic analyses of continuous traits, fitting a linear, mixed model; estimates of covariance components and the resulting genetic parameters are obtained by restricted maximum likelihood. A wide range of models, comprising numerous traits, multiple fixed and random effects, selected genetic covariance structures, random regression models and reduced rank estimation are accommodated. WOMBAT employs up-to-date numerical and computational methods. Together with the use of efficient compilers, this generates fast executable programs, suitable for large scale analyses. Use of WOMBAT is illustrated for a bivariate analysis. The package consists of the executable program, available for LINUX and WINDOWS environments, manual and a set of worked example, and can be downloaded free of charge from (http://agbu. une.edu.au/~kmeyer/wombat.html).
Animals ; Likelihood Functions ; Mice ; Models, Genetic ; Software

Secondary metabolites are produced during the growth and development of plants along with the adaptation of outer environment, as a rule they are the main active ingredients in medicinal plants and ensure the quality of crude drugs. Since biogenesis is quite complex, the production and accumulation of secondary metabolites are influenced by various biotic and abiotic factors either from gene or environments, the complexity may affect quality control of crude drugs and utilization of the active ingredients. The thought and approach adopted in systems biology is a powerful tool to explore biology fully, along with the development of modern molecular biology and information biology, omics integration like genomics, transcriptomics, proteomics, and metabolomics will bring new opportunities for the study of secondary metabolites of medicinal plant. It has great significance to apply this holistic and systematic method in researches on biosynthetic pathway, signal transduction, ecological environment and metabolic engineering of the formation of the secondary metabolites of medicinal plants, and in building secondary metabolite biosynthesis gene expression and regulation system model, in order to explain the origin of the active ingredients of medicinal plants, formation mechanism of the Chinese herbs, metabolic engineering effecting active ingredients of medicinal plants, and the rational exploitation and utilization of resources of medicinal plants systematically.
Models, Biological ; Models, Theoretical ; Plants, Medicinal ; metabolism ; Systems Biology ; methods

OBJECTIVETo develop and verify a model diet for consumers with high exposure to food chemicals.

METHODSBased on the assumption that a person might consume average amounts of several different foods but only two or three at high levels, a model diet were put forward to calculate the high exposures to certain food chemical.Important parameters of this model were selected by comparing the outputs of this model with those of a reference model-semi-probabilistic model that is based on individual data. The concentration data of lead, cadmium and mercury (45 832, 43 862 and 25 243 samples respectively) from the national risk surveillance for chemical contaminations and harmful factors (2011), and the consumption data from the national survey on nutrition and health status in Chinese population (2002) were used in this model optimization process. The final model was verified using concentration data of eight chemical contaminations from national surveillance database of 2010.

RESULTSWhen 90, 95 and 97.5 percentile exposure being calculated under the conditions that 7, 12, 20 and 30 food categories was used respectively, the model containing two high consumption foods (2+x model) got results lower than the reference values (the relative deviation < 0) , the model containing three high consumption foods (3+x model) got results higher than the reference values (the relative deviation > 0 ),but the relative deviation of the two models were both within 20%. The verification results showed that the dietary exposure results of 8 food contaminations got from 3+x model were all higher than and(or) close to those got from semi-probabilistic model, and the relative deviations were between -5% and 25%.

CONCLUSIONThe 3+x model diet can fulfill the demands of "conservative" and "accurate" on exposure assessment model, and can give reliable estimations of high exposure to food chemicals occurred in various food categories.

Endolymphatic hydrops is a representing pathologic finding of Ménière's disease. For the induction of endolymphatic hydrops in an animal model, surgical ablation of endolymphatic sac has been used. Although traditional model with the blockage of endolymphatic sac induced severe hydrops, it has several limitations for the study of pathophysiology of Ménière's disease. Recently, modified experimental models have been introduced, in which additional procedure was performed to induce the acute aggravation of hydrops after the surgical ablation. These new models could be helpful to elucidate the mechanism and develop a new treatment of Ménière's disease. In this review, we introduce the characteristics of animal models using surgical ablation of endolymphatic sac from the classical model to novel modified models.
Edema ; Endolymphatic Hydrops ; Endolymphatic Sac ; Meniere Disease ; Models, Animal ; Models, Theoretical

The study aimed to assess the single and joint lethal toxicity, type of interaction and the extent to which simple mathematical model of concentration addition (CA), independent action (IA) and generalized concentration addition (GCA) could predict the joint toxicity of copper hydroxide and glyphosate mixture in Clarias gariepinus. Static bioassay were setup to determine the individual and combined (based on ratio 1:2) lethal concentrations (LCx) of the pesticides. Data from the static bioassays were then fitted into the synergistic ratio (SR), concentration-addition (toxicity unit; TU) and isobologram model to determine the type of interaction between the different classes of pesticides, while the CA, IA and GCA models were used to predicted the observed mixture effects. The estimated 24 h, 48 h, 72 h and 96 h LC50 for copper hydroxide were 198.66 mg/L, 167.51 mg/L, 138.64 mg/L, and 104.82 mg/L; glyphosate were 162.92 mg/L, 103.88 mg/L, 61.95 mg/L, and 52.6l mg/L; while the mixtures were 63.18 mg/L, 59.06 mg/L, 56.42 mg/L, and 50.67 mg/L, respectively. Glyphosate was 2 times more toxic than copper hydroxide to C. gariepinus when acting singly. The SR and RTU was <1 indicate that the interaction between the pesticides was synergistic. Synergism was also corroborated by the isobologram model. The interaction of the mixture of copper hydroxide and glyphosate followed the IA model while the CA and GCA model underestimated the observed mixture effects. The study showed that copper hydroxide was practically non-toxic, while glyphosate and the mixture were slightly toxic to C. gariepinus
Biological Assay ; Catfishes ; Copper ; Joints ; Models, Theoretical ; Pesticides

The study aimed to assess the single and joint lethal toxicity, type of interaction and the extent to which simple mathematical model of concentration addition (CA), independent action (IA) and generalized concentration addition (GCA) could predict the joint toxicity of copper hydroxide and glyphosate mixture in Clarias gariepinus. Static bioassay were setup to determine the individual and combined (based on ratio 1:2) lethal concentrations (LCx) of the pesticides. Data from the static bioassays were then fitted into the synergistic ratio (SR), concentration-addition (toxicity unit; TU) and isobologram model to determine the type of interaction between the different classes of pesticides, while the CA, IA and GCA models were used to predicted the observed mixture effects. The estimated 24 h, 48 h, 72 h and 96 h LC50 for copper hydroxide were 198.66 mg/L, 167.51 mg/L, 138.64 mg/L, and 104.82 mg/L; glyphosate were 162.92 mg/L, 103.88 mg/L, 61.95 mg/L, and 52.6l mg/L; while the mixtures were 63.18 mg/L, 59.06 mg/L, 56.42 mg/L, and 50.67 mg/L, respectively. Glyphosate was 2 times more toxic than copper hydroxide to C. gariepinus when acting singly. The SR and RTU was <1 indicate that the interaction between the pesticides was synergistic. Synergism was also corroborated by the isobologram model. The interaction of the mixture of copper hydroxide and glyphosate followed the IA model while the CA and GCA model underestimated the observed mixture effects. The study showed that copper hydroxide was practically non-toxic, while glyphosate and the mixture were slightly toxic to C. gariepinus
Biological Assay ; Catfishes ; Copper ; Joints ; Models, Theoretical ; Pesticides