A copula method for modeling directional dependence of genes

<p>Abstract</p> <p>Background</p> <p>Genes interact with each other as basic building blocks of life, forming a complicated network. The relationship between groups of genes with different functions can be represented as gene networks. With the deposition of huge microarray data sets in public domains, study on gene networking is now possible. In recent years, there has been an increasing interest in the reconstruction of gene networks from gene expression data. Recent work includes linear models, Boolean network models, and Bayesian networks. Among them, Bayesian networks seem to be the most effective in constructing gene networks. A major problem with the Bayesian network approach is the excessive computational time. This problem is due to the interactive feature of the method that requires large search space. Since fitting a model by using the copulas does not require iterations, elicitation of the priors, and complicated calculations of posterior distributions, the need for reference to extensive search spaces can be eliminated leading to manageable computational affords. Bayesian network approach produces a discretely expression of conditional probabilities. Discreteness of the characteristics is not required in the copula approach which involves use of uniform representation of the continuous random variables. Our method is able to overcome the limitation of Bayesian network method for gene-gene interaction, i.e. information loss due to binary transformation.</p> <p>Results</p> <p>We analyzed the gene interactions for two gene data sets (one group is eight histone genes and the other group is 19 genes which include DNA polymerases, DNA helicase, type B cyclin genes, DNA primases, radiation sensitive genes, repaire related genes, replication protein A encoding gene, DNA replication initiation factor, securin gene, nucleosome assembly factor, and a subunit of the cohesin complex) by adopting a measure of directional dependence based on a copula function. We have compared our results with those from other methods in the literature. Although microarray results show a transcriptional co-regulation pattern and do not imply that the gene products are physically interactive, this tight genetic connection may suggest that each gene product has either direct or indirect connections between the other gene products. Indeed, recent comprehensive analysis of a protein interaction map revealed that those histone genes are physically connected with each other, supporting the results obtained by our method.</p> <p>Conclusion</p> <p>The results illustrate that our method can be an alternative to Bayesian networks in modeling gene interactions. One advantage of our approach is that dependence between genes is not assumed to be linear. Another advantage is that our approach can detect directional dependence. We expect that our study may help to design artificial drug candidates, which can block or activate biologically meaningful pathways. Moreover, our copula approach can be extended to investigate the effects of local environments on protein-protein interactions. The copula mutual information approach will help to propose the new variant of ARACNE (Algorithm for the Reconstruction of Accurate Cellular Networks): an algorithm for the reconstruction of gene regulatory networks.</p

Newborn Periventricular Nodular Heterotopia with Persistent Feeding Cyanosis and Apneic Spell: A Case Report

Periventricular nodular heterotopia (PNH) is a neuronal migration disorder that occurs during early brain development. Patients with PNH may be asymptomatic and have normal intelligence; however, PNH is also known to cause various symptoms such as seizures, dyslexia, and cardiovascular anomalies. PNH is not commonly diagnosed during early infancy because of the lack of clinical manifestations during this period. We present the case of a female infant diagnosed with PNH based on brain magnetic resonance imaging, who had symptomatic patent ductus arteriosus that had to be ligated surgically and had prolonged feeding cyanosis with frequent apneic spells

Primary tuberculosis appendicitis with mesenteric mass

Tuberculosis primarily affecting the appendix is extremely rare and the diagnosis is difficult. Here, we report the case of a 14-year-old healthy boy presenting with right lower quadrant abdominal pain. On computed tomography, the distended appendix with 3.3 × 2.7 cm mass located at the right side of the right iliac artery was detected. There was neither bowel wall thickening nor active lung lesion. After laparoscopic appendectomy with mass excision, histopathological examination revealed chronic granulomatous inflammation, with caseous necrosis of the appendix. We made a diagnosis of primary tuberculosis of appendix and administrated anti-tuberculosis medication

Early gastric cancer arising from heterotopic gastric mucosa in the gastric submucosa

The incidence of heterotopic gastric mucosa located in the submucosa in resected stomach specimens has been reported to be 3.0 to 20.1%. Heterotopic gastric mucosa is thought to be a benign disease, which rarely becomes malignant. Heterotopic gastric mucosa exists in the gastric submucosa, and gastric cancer rarely occurs in heterotopic gastric mucosa. Since tumors are located in the normal submucosa, they appear as submucosal tumors during endoscopy, and are diagnosed through endoscopic biopsies with some difficulty. For such reasons, heterotopic gastric mucosa is mistaken as gastric submucosal tumor. Recently, two cases of early gastric cancer arising from heterotopic gastric mucosa in the gastric submucosa were treated. Both cases were diagnosed as submucosal tumors based on upper gastrointestinal endoscopy, endoscopic ultrasound, and computed tomography findings, and in both cases, laparoscopic wedge resections were performed, the surgical findings of which also suggested submucosal tumors. However, pathologic assessment of the surgical specimens led to the diagnosis of well-differentiated intramucosal adenocarcinoma arising from heterotopic gastric mucosa in the gastric submucosa

Efficacy and safety of intragastric balloon for obesity in Korea

Background/Aims Intragastric balloon (IGB) is the only available endoscopic bariatric and metabolic therapy in Korea. End-ball (Endalis) has the longest history of clinical use among the IGBs available in Korea. However, little clinical data on this system have been reported. In this study, we aimed to evaluate the efficacy and safety of End-ball in Korea. Methods We performed a retrospective cohort study of patients who underwent IGB insertion (End-ball) from 2013 to 2019. Demographic and anthropometric data were collected. The efficacy and safety of IGB treatment were analyzed. Results In total, 80 patients were included. Mean age was 33.7 years and 83.8% were female. Initial body mass index was 34.48±4.69 kg/m2. Body mass index reduction was 3.72±2.63 kg/m2 at the time of IGB removal. Percent of total body weight loss (%TBWL) was 10.76%±6.76%. Percentage excess body weight loss was 43.67%±27.59%. Most adverse events were minor, and 71.4% of participants showed nausea, vomiting, or abdominal pain. Conclusions IGB treatment showed good efficacy and safety profile in Korean patients with obesity. In terms of %TBWL and percentage excess body weight loss, the efficacy was similar to that in the Western population

Nanostring-based multigene assay to predict recurrence for gastric cancer patients after surgery

10.1371/journal.pone.0090133PLoS ONE93-POLN