• Biomolecules & Therapeutics
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• 제30권1호
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• pp.98-116
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• 2022

The small GTPase RhoA has been studied extensively for its role in actin dynamics. In this study, multiple bioinformatics tools were applied cooperatively to the microarray dataset GSE64714 to explore previously unidentified functions of RhoA. Comparative gene expression analysis revealed 545 differentially expressed genes in RhoA-null cells versus controls. Gene set enrichment analysis (GSEA) was conducted with three gene set collections: (1) the hallmark, (2) the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and (3) the Gene Ontology Biological Process. GSEA results showed that RhoA is related strongly to diverse pathways: cell cycle/growth, DNA repair, metabolism, keratinization, response to fungus, and vesicular transport. These functions were verified by heatmap analysis, KEGG pathway diagramming, and direct acyclic graphing. The use of multiple gene set collections restricted the leakage of information extracted. However, gene sets from individual collections are heterogenous in gene element composition, number, and the contextual meaning embraced in names. Indeed, there was a limit to deriving functions with high accuracy and reliability simply from gene set names. The comparison of multiple gene set collections showed that although the gene sets had similar names, the gene elements were extremely heterogeneous. Thus, the type of collection chosen and the analytical context influence the interpretation of GSEA results. Nonetheless, the analyses of multiple collections made it possible to derive robust and consistent function identifications. This study confirmed several well-described roles of RhoA and revealed less explored functions, suggesting future research directions.

• Animal Bioscience
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• 제37권3호
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• pp.451-460
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• 2024

Objective: The objective is to identify genomic regions and candidate genes associated with age to 105 kg (AGE), average daily gain (ADG), backfat thickness (BF), and eye muscle area (EMA) in Yorkshire pig. Methods: This study used a total of 104,380 records and 11,854 single nucleotide polymorphism (SNP) data obtained from Illumina porcine 60K chip. The estimated genomic breeding values (GEBVs) and SNP effects were estimated by single-step genomic best linear unbiased prediction (ssGBLUP). Results: The heritabilities of AGE, ADG, BF, and EMA were 0.50, 0.49, 0.49, and 0.23, respectively. We identified significant SNP markers surpassing the Bonferroni correction threshold (1.68×10^-6), with a total of 9 markers associated with both AGE and ADG, and 4 markers associated with BF and EMA. Genome-wide association study (GWAS) analyses revealed notable chromosomal regions linked to AGE and ADG on Sus scrofa chromosome (SSC) 1, 6, 8, and 16; BF on SSC 2, 5, and 8; and EMA on SSC 1. Additionally, we observed strong linkage disequilibrium on SSC 1. Finally, we performed enrichment analyses using gene ontology and Kyoto encyclopedia of genes and genomes (KEGG), which revealed significant enrichments in eight biological processes, one cellular component, one molecular function, and one KEGG pathway. Conclusion: The identified SNP markers for productive traits are expected to provide valuable information for genetic improvement as an understanding of their expression.

• Journal of Animal Science and Technology
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• 제62권6호
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• pp.765-776
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• 2020

The retinal degenerative disease, progressive retinal atrophy (PRA) is a major reason of vision impairment in canine population. Canine PRA signifies an inherently dissimilar category of retinal dystrophies which has solid resemblances to human retinis pigmentosa. Even though much is known about the biology of PRA, the knowledge about the intricate connection among genetic loci, genes and pathways associated to this disease in dogs are still remain unknown. Therefore, we have performed a genome wide association study (GWAS) to identify susceptibility single nucleotide polymorphisms (SNPs) of PRA. The GWAS was performed using a case-control based association analysis method on PRA dataset of 129 dogs and 135,553 markers. Further, the gene-set and pathway analysis were conducted in this study. A total of 1,114 markers associations with PRA trait at p < 0.01 were extracted and mapped to 640 unique genes, and then selected significant (p < 0.05) enriched 35 gene ontology (GO) terms and 5 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways contain these genes. In particular, apoptosis process, homophilic cell adhesion, calcium ion binding, and endoplasmic reticulum GO terms as well as pathways related to focal adhesion, cyclic guanosine monophosphate)-protein kinase G signaling, and axon guidance were more likely associated to the PRA disease in dogs. These data could provide new insight for further research on identification of potential genes and causative pathways for PRA in dogs.

• 대한본초학회지
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• 제38권6호
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• pp.73-91
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• 2023

Objectives : This study used a network pharmacology approach to elucidate the efficacy and molecular mechanisms of Daehwangmokdanpitang (DHMDPT) on Psoriasis. Methods : Using OASIS databases and PubChem database, compounds of DHMDPT and their target genes were collected. The putative target genes of DHMDPT and known target genes of psoriasis were compared and found the correlation. Then, the network was constructed using Cytoscape 3.10.1. The key target genes were screened by Analyzer network and their functional enrichment analysis was conducted based on the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results : The result showed that total 30 compounds and 439 related genes were gathered from DHMDPT. 264 genes were interacted with psoriasis gene set, suggesting that the effects of DHMDPT are closely related to psoriasis. Based on GO enrichment analysis and KEGG pathways, 'Binding', 'Cytokine Activity', 'Receptor Ligand Activity' 'HIF-1 signaling pathway', 'IL-17 signaling pathway', 'Toll-like receptor signaling pathway', and 'TNF signaling pathway' were predicted as functional pathways of 16 key target genes of DHMDPT on psoriasis. Among the target genes, IL6, IL1B, TNF, AKT1 showed high correlation with the results of KEGG pathways. Additionally, Emodin, Acetovanillone, Gallic acid, and Ferulic acid showed a high relevance with key genes and their mechanisms. Conclusion : Through a network pharmacological method, DHMDPT was predicted to have high relevance with psoriasis. This study could be used as a basis for studying therapeutic effects of DHMDPT on psoriasis.

• Genomics & Informatics
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• 제20권2호
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• pp.20.1-20.13
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• 2022

Recent studies have focused on the early detection of ovarian cancer (OC) using tumor materials by liquid biopsy. The mechanisms of microRNAs (miRNAs) to impact OC and signaling pathways are still unknown. This study aims to reliably perform functional analysis of previously validated circulating miRNAs' target genes by using pathfindR. Also, overall survival and pathological stage analyses were evaluated with miRNAs' target genes which are common in the The Cancer Genome Atlas and GTEx datasets. Our previous studies have validated three downregulated miRNAs (hsa-miR-885-5p, hsa-miR-1909-5p, and hsa-let7d-3p) having a diagnostic value in OC patients' sera, with high-throughput techniques. The predicted target genes of these miRNAs were retrieved from the miRDB database (v6.0). Active-subnetwork-oriented Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted by pathfindR using the target genes. Enrichment of KEGG pathways assessed by the analysis of pathfindR indicated that 24 pathways were related to the target genes. Ubiquitin-mediated proteolysis, spliceosome and Notch signaling pathway were the top three pathways with the lowest p-values (p < 0.001). Ninety-three common genes were found to be differentially expressed (p < 0.05) in the datasets. No significant genes were found to be significant in the analysis of overall survival analyses, but 24 genes were found to be significant with pathological stages analysis (p < 0.05). The findings of our study provide in-silico evidence that validated circulating miRNAs' target genes and enriched pathways are related to OC and have potential roles in theranostics applications. Further experimental investigations are required to validate our results which will ultimately provide a new perspective for translational applications in OC management.

• Genomics & Informatics
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• 제6권4호
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• pp.202-209
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• 2008

Biological pathways are known as collections of knowledge of certain biological processes. Although knowledge about a pathway is quite significant to further analysis, it covers only tiny portion of genes that exists. In this paper, we suggest a model to extend each individual pathway using a microarray expression data based on the known knowledge about the pathway. We take the Rosetta compendium dataset to extend pathways of Saccharomyces cerevisiae obtained from KEGG (Kyoto Encyclopedia of genes and genomes) database. Before applying our model, we verify the underlying assumption that microarray data reflect the interactive knowledge from pathway, and we evaluate our scoring system by introducing performance function. In the last step, we validate proposed candidates with the help of another type of biological information. We introduced a pathway extending model using its intrinsic structure and microarray expression data. The model provides the suitable candidate genes for each single biological pathway to extend it.

• Genomics & Informatics
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• 제10권1호
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• pp.9-15
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• 2012

Horizontal gene transfer (HGT) is the movement of genetic material between kingdoms and is considered to play a positive role in adaptation. $Cryptosporidium$ $parvum$ is a parasitic protozoan that causes an infectious disease. Its genome sequencing reported 14 bacteria-like proteins in the nuclear genome. Among them, cgd2_1810, which has been annotated as CysQ, a sulfite synthesis pathway protein, is listed as one of the candidates of genes horizontally transferred from bacterial origin. In this report, we examined this issue using phylogenetic analysis. Our BLAST search showed that $C.$ $parvum$ CysQ protein had the highest similarity with that of proteobacteria. Analysis with NCBI's Conserved Domain Tree showed phylogenetic incongruence, in that $C.$ $parvum$ CysQ protein was located within a branch of proteobacteria in the cd01638 domain, a bacterial member of the inositol monophosphatase family. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, the sulfate assimilation pathway, where CysQ plays an important role, is well conserved in most eukaryotes as well as prokaryotes. However, the Apicomplexa, including $C.$ $parvum$, largely lack orthologous genes of the pathway, suggesting its loss in those protozoan lineages. Therefore, we conclude that $C.$ $parvum$ regained cysQ from proteobacteria by HGT, although its functional role is elusive.

• Asian-Australasian Journal of Animal Sciences
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• 제32권2호
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• pp.290-296
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• 2019

Objective: Pigs share many physiological, anatomical and genomic similarities with humans, which make them suitable models for biomedical researches. Understanding the genetic status of Yucatan miniature pigs (YMPs) and their association with human diseases will help to assess their potential as biomedical model animals. This study was performed to identify non-synonymous single nucleotide polymorphisms (nsSNPs) in selective sweep regions of the genome of YMPs and present the genetic nsSNP distributions that are potentially associated with disease occurrence in humans. Methods: nsSNPs in whole genome resequencing data from 12 YMPs were identified and annotated to predict their possible effects on protein function. Sorting intolerant from tolerant (SIFT) and polymorphism phenotyping v2 analyses were used, and gene ontology (GO) network and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed. Results: The results showed that 8,462 genes, encompassing 72,067 nsSNPs were identified, and 118 nsSNPs in 46 genes were predicted as deleterious. GO network analysis classified 13 genes into 5 GO terms (p<0.05) that were associated with kidney development and metabolic processes. Seven genes encompassing nsSNPs were classified into the term associated with Alzheimer's disease by referencing the genetic association database. The KEGG pathway analysis identified only one significantly enriched pathway (p<0.05), hsa04080: Neuroactive ligand-receptor interaction, among the transcripts. Conclusion: The number of deleterious nsSNPs in YMPs was identified and then these variants-containing genes in YMPs data were adopted as the putative human diseases-related genes. The results revealed that many genes encompassing nsSNPs in YMPs were related to the various human genes which are potentially associated with kidney development and metabolic processes as well as human disease occurrence.

• Molecules and Cells
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• 제21권2호
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• pp.269-275
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• 2006

A recent report of the Korean Intellectual Property Office(KIPO) showed that the number of biological sequence-based patents is rapidly increasing in Korea. We present biological features of Korean patented sequences though bioinformatic analysis. The analysis is divided into two steps. The first is an annotation step in which the patented sequences were annotated with the Reference Sequence (RefSeq) database. The second is an association step in which the patented sequences were linked to genes, diseases, pathway, and biological functions. We used Entrez Gene, Online Mendelian Inheritance in Man (OMIM), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) databases. Through the association analysis, we found that nearly 2.6% of human genes were associated with Korean patenting, compared to 20% of human genes in the U.S. patent. The association between the biological functions and the patented sequences indicated that genes whose products act as hormones on defense responses in the extra-cellular environments were the most highly targeted for patenting. The analysis data are available at http://www.patome.net

• 대한한의학회지
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• 제31권4호
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• pp.79-100
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• 2010

Objective: Production of ROS from glucose toxicity results in injury of pancreatic $\beta$-cells in diabetes models. This study was undertaken to examine the influence of Lespedeza Cuneata extract (LCE) on cytoprotective effects on glucose toxicity, insulin secretion and gene expression in RIN-m5F cells. Methods: First, we measured LCE's antioxidant activity by DPPH free radical-scavenging activity and SOD activity. After the various concentrations of LCE were added to the RIN-m5F cells, we measured cell viability with glucose stimulation by MTT assay and glucose-stimulated insulin secretion. We analyzed gene expression with Agilent whole mouse genome 44K oligo DNA microarray and searched for related pathways in KEGG (Kyoto Encyclopedia of Genes and Genomes). Lastly we measured INS-1, INS-2, INS-R, IRS-1, IRS-2, IRS-3, GLP-1R, and GLP-2R mRNA expression by real time RT-PCR. Results: Free radical-scavenging activity, SOD activity and insulin secretion increased dependent on LCE concentration, but LCE did not show considerable cytoprotective effect on RIN-m5F cells. More than twice expressed gene was 6362 in Oligo DNA chip. In KEGG, the most related pathway was the metabolic pathway. In the insulin signaling pathway, up expressed genes were Irs1, Mapk8, Akt1, and Lipe and down expressed genes were Rhoq, Fbp2, Prkar2b, Gck, and Prkag1. In real time RT-PCR, IRS-2, and IRS-3 expression increased significantly compared to the control group on LCE $12{\mu}g/m{\ell}$ concentration and GCK expression decreased significantly compared to the control group. Conclusions: These results show that LCE encourages insulin secretion and insulin metabolism by complicated gene mechanisms. Further mechanism study and clinical study seem to be necessary about Lespedeza Cuneata.