A NEW METHOD OF DETERMINING THRESHOLD OF GENE NETWORK BASED ON PHENOTYPES

2011 ◽  
Vol 19 (04) ◽  
pp. 607-616
Author(s):  
YUANYUAN ZHANG ◽  
SHUDONG WANG ◽  
MEIXI YANG ◽  
DASHUN XU ◽  
DAZHI MENG
Keyword(s):  
Gene Networks ◽  
Gene Network ◽  
Structural Parameters ◽  
Network Modeling ◽  
Genetic Diseases ◽  
Disease Stage ◽  
External Representation ◽  
Functional Relationships ◽  
Disease Phenotypes ◽  
Significant Difference

With the rapid growth of microarray data, it has become a hot topic to reveal complex behaviors and functions of life system by studying the relationships among genes. In the process of reverse network modeling, the relationships with less relevance are generally not considered by determining a threshold when the relationships among genes are mined. However, there are no effective methods to determine the threshold up to now. It is worthwhile to note that the phenotypes of genetic diseases are generally regarded as external representation of the functions of genes. Therefore, two types of phenotype networks are constructed from gene and disease views, respectively, and through comparing these two types of phenotype networks, the threshold of gene network corresponding to a certain disease can be determined when their similarity reaches to maximum. Because the gene network is determined based on the relationships among phenotypes and phenotypes are external representation of the functions of genes, it is considered that relationships in the gene network may show functional relationships among genes in biological system. In this work, the thresholds 0.47 and 0.48 of gene network are determined based on Parkinson disease phenotypes. Furthermore, the validity of these thresholds is verified by the specificity and susceptibility of phenotype networks. Also, through comparing the structural parameters of gene networks for normal and disease stage at different thresholds, significant difference between the two gene networks at threshold 0.47 or 0.48 is found. The significant difference of structural parameters further verifies the efficiency of this method.

A study of structural properties of gene network graphs for mathematical modeling of integrated mosaic gene networks

2017 ◽  
Vol 15 (02) ◽  
pp. 1650045 ◽  
Author(s):  
Olga V. Petrovskaya ◽  
Evgeny D. Petrovskiy ◽  
Inna N. Lavrik ◽  
Vladimir A. Ivanisenko
Keyword(s):  
Mathematical Modeling ◽  
Gene Regulatory Networks ◽  
Gene Networks ◽  
Gene Network ◽  
Regulatory Networks ◽  
Network Modeling ◽  
Computer Experiments ◽  
Linear Control ◽  
Expression Of Genes ◽  
Gene Regulatory

Gene network modeling is one of the widely used approaches in systems biology. It allows for the study of complex genetic systems function, including so-called mosaic gene networks, which consist of functionally interacting subnetworks. We conducted a study of a mosaic gene networks modeling method based on integration of models of gene subnetworks by linear control functionals. An automatic modeling of 10,000 synthetic mosaic gene regulatory networks was carried out using computer experiments on gene knockdowns/knockouts. Structural analysis of graphs of generated mosaic gene regulatory networks has revealed that the most important factor for building accurate integrated mathematical models, among those analyzed in the study, is data on expression of genes corresponding to the vertices with high properties of centrality.

scholarly journals Platelet Depletion is Effective in Ameliorating Anxiety-Like Behavior and Reducing the Pro-Inflammatory Environment in the Hippocampus in Murine Experimental Autoimmune Encephalomyelitis

2019 ◽  
Vol 8 (2) ◽  
pp. 162 ◽  
Author(s):  
Pece Kocovski ◽  
Xiangrui Jiang ◽  
Claretta D’Souza ◽  
Zhenjiang Li ◽  
Phuc Dang ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Neuropsychiatric Symptoms ◽  
Critical Role ◽  
Clinical Manifestations ◽  
Lymphocytic Infiltration ◽  
Disease Stage ◽  
Autoimmune Encephalomyelitis ◽  
Significant Difference ◽  
Platelet Depletion ◽  
Experimental Autoimmune

The neuropsychiatric symptoms of multiple sclerosis (MS), such as anxiety and depression, can result from disease activity itself as well as psychological reaction to an unfavorable diagnosis. Accordingly, the literature reports evidence of increased anxiety-like behavior in experimental autoimmune encephalomyelitis (EAE), an accepted MS model. Due to the recently described critical role of platelets in inflammation and autoimmune disease, we examined the relationship between platelets, inflammation, and anxiety-like behavior in EAE. In the elevated plus maze, EAE-induced C57BL/6J mice showed decreased time spent in the open arms relative to vehicle-only controls, demonstrating an increase in anxiety-like behavior. This effect occurred in the presence of platelet–neuron association, but absence of lymphocytic infiltration, in the hippocampal parenchyma. Platelet depletion at the pre-clinical disease stage, using antibody-mediated lysis prevented the EAE-induced increase in anxiety-like behavior, while no significant difference in distance moved was recorded. Furthermore, platelet depletion was also associated with reduction of the pro-inflammatory environment to control levels in the hippocampus and prevention of EAE disease symptomology. These studies demonstrate the high efficacy of a platelet-targeting approach in preventing anxiety-like symptoms and clinical manifestations of EAE and have implications for the treatment of neuropsychiatric symptoms in MS.

scholarly journals Genome-wide inferring gene–phenotype relationship by walking on the heterogeneous network

2010 ◽  
Vol 26 (9) ◽  
pp. 1219-1224 ◽  
Author(s):  
Yongjin Li ◽  
Jagdish C. Patra
Keyword(s):  
Heterogeneous Network ◽  
Gene Network ◽  
Genetic Diseases ◽  
Supplementary Information ◽  
Disease Genes ◽  
Phenotypic Data ◽  
Disease Associations ◽  
Improved Performance ◽  
Leave One Out ◽  
Phenotype Network

Abstract Motivation: Clinical diseases are characterized by distinct phenotypes. To identify disease genes is to elucidate the gene–phenotype relationships. Mutations in functionally related genes may result in similar phenotypes. It is reasonable to predict disease-causing genes by integrating phenotypic data and genomic data. Some genetic diseases are genetically or phenotypically similar. They may share the common pathogenetic mechanisms. Identifying the relationship between diseases will facilitate better understanding of the pathogenetic mechanism of diseases. Results: In this article, we constructed a heterogeneous network by connecting the gene network and phenotype network using the phenotype–gene relationship information from the OMIM database. We extended the random walk with restart algorithm to the heterogeneous network. The algorithm prioritizes the genes and phenotypes simultaneously. We use leave-one-out cross-validation to evaluate the ability of finding the gene–phenotype relationship. Results showed improved performance than previous works. We also used the algorithm to disclose hidden disease associations that cannot be found by gene network or phenotype network alone. We identified 18 hidden disease associations, most of which were supported by literature evidence. Availability: The MATLAB code of the program is available at http://www3.ntu.edu.sg/home/aspatra/research/Yongjin_BI2010.zip Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

scholarly journals On Robust State Estimation of Gene Networks

2010 ◽  
Vol 2 ◽  
pp. 117959721000200 ◽  
Author(s):  
Chia-Hua Chuang ◽  
Chun-Liang Lin
Keyword(s):  
Parameter Estimation ◽  
Kalman Filter ◽  
Quantitative Analysis ◽  
State Estimation ◽  
Gene Networks ◽  
Gene Network ◽  
Biological Systems ◽  
Uncertain Process ◽  
Network Systems ◽  
Internal States

Gene networks in biological systems are not only nonlinear but also stochastic due to noise corruption. How to accurately estimate the internal states of the noisy gene networks is an attractive issue to researchers. However, the internal states of biological systems are mostly inaccessible by direct measurement. This paper intends to develop a robust extended Kalman filter for state and parameter estimation of a class of gene network systems with uncertain process noises. Quantitative analysis of the estimation performance is conducted and some representative examples are provided for demonstration.

Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis

2010 ◽  
Vol 42A (4) ◽  
pp. 267-282 ◽  
Author(s):  
U. Ungethuem ◽  
T. Haeupl ◽  
H. Witt ◽  
D. Koczan ◽  
V. Krenn ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell Activation ◽  
Gene Networks ◽  
Cell Activation ◽  
Joint Disease ◽  
Disease Stage ◽  
Unknown Etiology ◽  
Coxa Vara ◽  
Molecular Signatures ◽  
Loss Of Function

Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced interpatient heterogeneity. To characterize RA at the molecular level and to uncover pathomechanisms, we performed genome-wide gene expression analysis. We identified a set of 1,054 genes significantly deregulated in pair-wise comparisons between RA and osteoarthritis (OA) patients, RA and normal donors (ND), or OA and ND. Correlation analysis revealed gene sets regulated identically in all three groups. As a prominent example secreted phosphoprotein 1 (SPP1) was identified to be significantly upregulated in RA compared with both OA and ND. SPP1 expression was found to correlate with genes expressed during an inflammatory response, T-cell activation and apoptosis, suggesting common underlying regulatory networks. A subclassification of RA patients was achieved on the basis of proteoglycan 4 (PRG4) expression, distinguishing PRG4 high and low expressors and reflecting the heterogeneity of the disease. In addition, we found that low PRG4 expression was associated with a more aggressive disease stage, which is in accordance with PRG4 loss-of-function mutations causing camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Altogether we provide evidence for molecular signatures of RA and RA subclasses, sets of new candidate genes as well as for candidate gene networks, which extend our understanding of disease mechanisms and may lead to an improved diagnosis.

scholarly journals Differences in the outcomes of adjuvant chemotherapy for colon cancer prescribed by physicians in different disciplines: a population-based study in Taiwan

BMJ Open ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. e021341
Author(s):  
Cheng-I Hsieh ◽  
Raymond Nien-Chen Kuo ◽  
Chun-Chieh Liang ◽  
Hsin-Yun Tsai ◽  
Kuo-Piao Chung
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Surgical Margin ◽  
Disease Free Survival ◽  
Disease Stage ◽  
Multiple Primary Cancers ◽  
Positive Surgical Margin ◽  
Recurrence Rates ◽  
Significant Difference

ObjectivesOne feature unique to the Taiwanese healthcare system is the ability of physicians other than oncologists to prescribe systemic chemotherapy. This study investigated whether the care paths implemented by oncologists and non-oncologists differ with regard to patient outcomes.SettingData from the Taiwan Cancer Registry and National Health Insurance Database were linked to identify patients with colon cancer who underwent colectomy as first treatment within 3 months of diagnosis and adjuvant chemotherapy between 2005 and 2009.Participants and methodsPostoperative patients who underwent adjuvant chemotherapy were included in this study. The exclusion criteria included patients with stage IV disease, a positive surgical margin and early disease recurrence. Among the patients presenting with multiple primary cancers, we also excluded patients who were diagnosed with colon cancer but for whom this was not the first primary cancer. The variables included sex, age, comorbidities, disease stage, chemotherapy cycle and changes in treatment regimen as well as the specialty of treatment providers and their case volume. Cox regression models and Kaplan-Meier analysis were used to examine differences in outcomes in the matched cohorts.ResultsWe examined 3534 patients who were prescribed adjuvant chemotherapy by physicians from different disciplines. In terms of 5-year disease-free survival, no significant difference was observed between the groups of oncologists or surgeons among patients with stage II (90.02%vs88.99%) or stage III (77.64%vs79.99%) diseases. Patients who were subjected to changes in their chemotherapy regimens presented recurrence rates higher than those who were not.ConclusionsThe discipline of practitioners is seldom taken into account in most series. This is the first study to provide empirical evidence demonstrating that the outcomes of patients with colon cancer do not depend on the treatment path, as long as the selection criteria for adjuvant chemotherapy is appropriate. Further study will be required before making any further conclusions.

scholarly journals The assessment of the stability of the corneal structure after LASIK correction of myopia by different optical zone diameters

2016 ◽  
Vol 73 (6) ◽  
pp. 572-576 ◽  
Author(s):  
Milorad Milivojevic ◽  
Vladimir Petrovic ◽  
Miroslav Vukosavljevic ◽  
Ivan Marjanovic ◽  
Mirko Resan
Keyword(s):  
Structural Parameters ◽  
Preoperative Assessment ◽  
Laser In Situ Keratomileusis ◽  
Group I ◽  
Significant Difference ◽  
Optical Zone ◽  
Corneal Structure ◽  
The Stability ◽  
Corneal Thinning

Background/Aim. Enlargement of optical zone (OZ) diameter during laser in situ keratomileusis (LASIK) correction of myopia postoperatively improves the optical outcome, however, it also leads to the increased stroma tissue consumption - progressive corneal thinning. The aim of this investigation was to present the possibility of safe OZ enlargement without impairing the structural stability of the cornea, while obtaining an improved optical outcome with LASIK treatment of shortsightedness. Methods. Preoperative assessment of the cornea structure and prediction of the ablated stroma tissue consumption was conducted in 37 patients (74 eyes) treated for shortsightedness by means of the LASIK method. With the eyes that, according to their cornea structure, had the capacity for OZ diameter enlargement of 0.5 mm, LASIK treatment was performed within the wider OZ diameter of 7.0 mm compared to the standard 6.5 mm. The following two groups were formed, depending on the diameter of the utilized OZ: the group I (the eyes treated with the OZ 6.5 mm, n = 37) and the group II (the eyes treated with the OZ 7.0 mm, n = 37). Results. No significant difference in the observed structural parameters of the cornea was detected between the groups of patients treated with different OZ diameters. The values of all the parameters were significantly bellow the threshold values for the development of postoperative ectasia. Conclusion. Diameter enlargement of the treated OZ, if there is a preoperative cornea capacity for such enlargement, will not impair the postoperative stability of the cornea structure, and will significantly improve the optical outcome.

scholarly journals An investigation on the frequency of thoughts, readiness and suicide attempt in individuals with thalassemia

2021 ◽  
Vol 15 (6) ◽  
pp. 1847-1853
Author(s):  
Sahar Attar ◽  
Nour Mohammad Bakhshani ◽  
Qasem Miri Aliabad
Keyword(s):  
Suicidal Ideation ◽  
Suicide Attempts ◽  
Statistical Tests ◽  
Genetic Diseases ◽  
Thalassemia Major ◽  
Cross Sectional Study ◽  
World Health ◽  
Cross Sectional ◽  
Significant Difference ◽  
The World

Background and Aim: Thalassemia major is one of the most common chronic genetic diseases in the world and in Iran that can impose many adverse effects on the self and society. Psychologically, patients with thalassemia are under stress. According to the World Health Organization (WHO), suicide is one of the leading causes of death worldwide. It is important to identify the people who have the highest risk factors for suicide. The present research investigates the frequency of thoughts, readiness and suicide attempts in people with thalassemia. Methods: This was a cross-sectional study. Its sample was 150 patients with thalassemia in the age range of 10 to 46 years whom we selected through census by sampling at convenience. We gave to patients a standardized Beck Suicide Thought Assessment Questionnaire. We analyzed the research data using descriptive and inferential statistical tests. Results: From among 150 patients with thalassemia in this study, 57.3% of the respondents were male and 42.7% were female. The results showed that there was a negative and significant relationship between suicide thoughts and attempts and age (-0.234) (P <0.05). The mean prevalence of suicide in men (1.89) was significantly higher compared to women (0.79) (P <0.05). We did not observe significant difference in prevalence of suicide thoughts and attempts between married and single groups with a mean difference (0.69) (P <0.05) and, in different educational groups, no significant difference was reported (P> 0.05). Conclusion: The findings of this research showed that among patients with thalassemia, the prevalence of suicidal ideation has a significant percentage. Since suicidal ideation provides a platform for preparation and attempt to commit suicide, so by providing mental health services and regular screening, we can take an effective step to prevent this problem among patients with thalassemia. Keywords: Thalassemia, Suicidal ideation, Suicide.

scholarly journals Network Structure Analysis Identifying Key Genes of Autism and Its Mechanism

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yanhui Wang ◽  
Yanming Kou ◽  
Dazhi Meng
Keyword(s):  
Expression Profiles ◽  
Structural Parameters ◽  
Enrichment Analysis ◽  
Average Degree ◽  
Control Group ◽  
Original Research ◽  
Cardiovascular Development ◽  
Correlation Networks ◽  
Significant Difference ◽  
Key Genes

Identifying the key genes of autism is of great significance for understanding its pathogenesis and improving the clinical level of medicine. In this paper, we use the structural parameters (average degree) of gene correlation networks to identify genes related to autism and study its pathogenesis. Based on the gene expression profiles of 82 autistic patients (the experimental group, E) and 64 healthy persons (the control group, C) in NCBI database, spearman correlation networks are established, and their average degrees under different thresholds are analyzed. It is found that average degrees of C and E are basically separable at the full thresholds. This indicates that there is a clear difference between the network structures of C and E, and it also suggests that this difference is related to the mechanism of disease. By annotating and enrichment analysis of the first 20 genes (MD-Gs) with significant difference in the average degree, we find that they are significantly related to gland development, cardiovascular development, and embryogenesis of nervous system, which support the results in Alter et al.’s original research. In addition, FIGF and CSF3 may play an important role in the mechanism of autism.

scholarly journals The Role of a “Treat-to-Target” Approach in the Long-Term Renal Outcomes of Patients with Gout

2019 ◽  
Vol 8 (7) ◽  
pp. 1067
Author(s):  
Woo-Joong Kim ◽  
Jung Soo Song ◽  
Sang Tae Choi
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Chronic Kidney Disease Stage ◽  
Multivariable Analysis ◽  
Serum Urate ◽  
Disease Stage ◽  
Treat To Target ◽  
Renal Outcomes ◽  
Significant Difference

Background: Although gout is accompanied by the substantial burden of kidney disease, there are limited data to assess renal function as a therapeutic target. This study evaluated the importance of implementing a “treat-to-target” approach in relation to renal outcomes. Methods: Patients with gout who underwent continuous urate-lowering therapy (ULT) for at least 12 months were included. The effect of ULT on renal function was investigated by means of a sequential comparison of the estimated glomerular filtration rate (eGFR). Results: Improvement in renal function was only demonstrated in subjects in whom the serum urate target of <6 mg/dL was achieved (76.40 ± 18.81 mL/min/1.73 m2 vs. 80.30 ± 20.41 mL/min/1.73 m2, p < 0.001). A significant difference in the mean change in eGFR with respect to serum urate target achievement was shown in individuals with chronic kidney disease stage 3 (−0.35 ± 3.87 mL/min/1.73 m2 vs. 5.33 ± 11.64 mL/min/1.73 m2, p = 0.019). Multivariable analysis predicted that patients ≥65 years old had a decreased likelihood of improvement (OR 0.31, 95% CI 0.13–0.75, p = 0.009). Conclusions: The “treat-to-target” approach in the long-term management of gout is associated with better renal outcomes, with a greater impact on those with impaired renal function.

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