• Molecules and Cells
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• v.42 no.8
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• pp.579-588
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• 2019

Gene set enrichment analysis (GSEA) is a popular tool to identify underlying biological processes in clinical samples using their gene expression phenotypes. GSEA measures the enrichment of annotated gene sets that represent biological processes for differentially expressed genes (DEGs) in clinical samples. GSEA may be suboptimal for functional gene sets; however, because DEGs from the expression dataset may not be functional genes per se but dysregulated genes perturbed by bona fide functional genes. To overcome this shortcoming, we developed network-based GSEA (NGSEA), which measures the enrichment score of functional gene sets using the expression difference of not only individual genes but also their neighbors in the functional network. We found that NGSEA outperformed GSEA in identifying pathway gene sets for matched gene expression phenotypes. We also observed that NGSEA substantially improved the ability to retrieve known anti-cancer drugs from patient-derived gene expression data using drug-target gene sets compared with another method, Connectivity Map. We also repurposed FDA-approved drugs using NGSEA and experimentally validated budesonide as a chemical with anti-cancer effects for colorectal cancer. We, therefore, expect that NGSEA will facilitate both pathway interpretation of gene expression phenotypes and anti-cancer drug repositioning. NGSEA is freely available at www.inetbio.org/ngsea.

• Genomics & Informatics
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• v.17 no.1
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• pp.10.1-10.3
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• 2019

To identify miRNA-mRNA interaction pairs associated with binary phenotypes, we propose a hierarchical structural component model for miRNA-mRNA integration (HisCoM-mimi). Information on known mRNA targets provided by TargetScan is used to perform HisCoM-mimi. However, multiple databases can be used to find miRNA-mRNA signatures with known biological information through different algorithms. To take these additional databases into account, we present our advanced application software for HisCoM-mimi for binary phenotypes. The proposed HisCoM-mimi supports both TargetScan and miRTarBase, which provides manually-verified information initially gathered by text-mining the literature. By integrating information from miRTarBase into HisCoM-mimi, a broad range of target information derived from the research literature can be analyzed. Another improvement of the new HisCoM-mimi approach is the inclusion of updated algorithms to provide the lasso and elastic-net penalties for users who want to fit a model with a smaller number of selected miRNAs and mRNAs. We expect that our HisCoM-mimi software will make advanced methods accessible to researchers who want to identify miRNA-mRNA interaction pairs related with binary phenotypes.

• The korean journal of orthodontics
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• v.50 no.6
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• pp.407-417
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• 2020

Objective: To investigate the dental phenotypes and treatment modalities (Tx-Mod) in Korean patients with Parry-Romberg syndrome (PRS) using longitudinal data. Methods: The samples consisted of 10 PRS patients, who were treated and/or followed-up at Seoul National University Dental Hospital between 1998 and 2019. Using a novel PRS severity index based on the numbers of the atrophy-involved area and asymmetry-involved item, we classified them into mild (n = 3), moderate (n = 2), and severe (n = 5). Dental phenotypes, including congenitally missing tooth (Con-Missing-Tooth), microdontia, tooth with short root (Short-Root), tooth with dilacerated root, and delayed eruption/impacted tooth, were investigated along with Tx-Mod. Results: The side of occurrence of all dental phenotypes showed 100% concordance with the side of PRS involvement. The most two common dental phenotypes were Con-Missing-Tooth and Short-Root (n = 29 and n = 17 in six patients). The sums of the average number of Con-Missing-Tooth and Short-Root increased from mild PRS to moderate PRS and severe PRS cases (1.0, 6.0, and 6.2). In terms of Tx-Mod, growth observation due to mild atrophy, fixed orthodontic treatment, and grafting were used for mild PRS cases. Tx-Mod for moderate PRS cases involved growth observation for surgery due to an early age at the initial visit. For severe PRS cases, diverse Tx-Mod combinations including unilateral functional appliance, fixed orthodontic treatment, growth observation, grafting, and orthognathic surgery were used. Conclusions: The novel PRS severity index may be useful to provide primary data for individualized diagnosis and treatment planning for PRS patients.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.487-492
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• 1994

The study was conducted to investigate the phenotypes of blood proteins, hemoglobin and albumin, of 104 German shepherds in Dag-gu, Yae-chum Kim-hae and Kwang-ju area by the starch gel electrophoresis. The results obtained were summarized as follows: 1. The hemoglobin phenotypes were observed three(HbBB, HbBb and Hbbb). Fast migrating bands were same and slow migrating bands were divided by heavy(HbBB), light(HbBb) and non-stained(Hbbb). The frequencies of appearance in HbBB, HbBb and Hbbb were 17.31%, 51.92% and 30.77%, respectively. 2. The hemoglobin phenotypes were controlled by two allelic genes, $Hb^b$ and $Hb^B$. The gene frequencies were calculated at 0.567 in $Hb^B$ and 0.433 in $Hb^A$. 3. The albumin phenotypes were observed three(AlbFF, AlbSS and and AlbFS), which were divided by fast migrating band(AlbFF), slow migrating band(AlbSS) and mixed migrating band(AlbFS). The frequencies of appearance in AlbFF, AlbFS and AlbSS were 5.77%, 28.85% and 65.38%, respectively. 4. The albumin phenotypes were controlled by two alleic genes, $Alb^F$ and $Alb^S$. The gene frequencies were calculated at 0.202 in $Alb^F$ and 0.798 in $Alb^S$.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.10
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• pp.1268-1275
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• 2010

Post-weaning diarrhoea (PWD) and oedema disease (ED) caused by E. coli F18 always result in economic losses to pig producers, and no effective methods of controlling PWD and ED are presently available. FUT1 has been identified as a candidate gene controlling the expression of E. coli F18 receptor. This study examined the correlation between F18ab and F18ac adhesion phenotypes and the polymorphism at position M307 of the FUT1 gene in three pig breeds (231 Large White, 107 Landrace and 109 Songliao Black). The results showed: i) Both the susceptible genotypes (GG and GA) and the adhesion phenotypes (adhesive or weekly adhesive) were dominant in all three breeds with frequencies over 95%. ii) Three adhesion patterns of the two F18 variants F18ab and F18ac, i.e., ($ab^+$, $ac^+$), ($ab^+$, $ac^-$) and ($ab^-$, $ac^-$), were found in all three breeds, and there was no significant difference in the distribution of adhesion phenotypes of the two variants (separately or jointly) among the three breeds (p>0.05). iii) The FUT1 M307 genotypes were completely associated with the F18ab adhesion phenotypes and very strongly associated with the F18ac adhesion phenotypes. All individuals of genotype AA were non-adhesive to both F18ab and F18ac. All individuals of genotype GG or GA were adhesive to F18ab, whereas 11% of them were non-adhesive to F18ac. These results suggest that the polymorphism at FUT1 M307 can be used for marker-assisted selection of PWD and ED resistant pigs.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.144-153
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• 2021

Astrocytes play various important roles such as maintaining brain homeostasis, supporting neurons, and secreting inflammatory mediators to protect the brain cells. In aged subjects, astrocytes show diversely changed phenotypes and dysfunctions. But, the study of aged astrocytes or astrocytes from aged subjects is not yet sufficient to provide a comprehensive understanding of their important processes in the regulation of brain function. In this study, we induced an in vitro aged astrocyte model through late passage cultivation of rat primary cultured astrocytes. Astrocytes were cultured until passage 7 (P7) as late passage astrocytes and compared with passage 1 (P1) astrocytes as early passage astrocytes to confirm the differences in phenotypes and the effects of serial passage. In this study, we confirmed the morphological, molecular, and functional changes of late passage astrocytes showing aging phenotypes through SA-β-gal staining and measurement of nuclear size. We also observed a reduced expression of inflammatory mediators including IL-1β, IL-6, TNFα, iNOS, and COX2, as well as dysregulation of wound-healing, phagocytosis, and mitochondrial functions such as mitochondrial membrane potential and mitochondrial oxygen consumption rate. Culture-conditioned media obtained from P1 astrocytes promoted neurite outgrowth in immature primary cultures of rat cortices, which is significantly reduced when we treated the immature neurons with the culture media obtained from P7 astrocytes. These results suggest that late passage astrocytes show senescent astrocyte phenotypes with functional defects, which makes it a suitable model for the study of the role of astrocyte senescence on the modulation of normal and pathological brain aging.

• BMB Reports
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• v.48 no.7
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• pp.373-379
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• 2015

Humans have acquired many distinct evolutionary traits after the human-chimpanzee divergence. These phenotypes have resulted from genetic changes that occurred in the human genome and were retained by natural selection. Comparative primate genome analyses reveal that loss-of-function mutations are common in the human genome. Some of these gene inactivation events were revealed to be associated with the emergence of advantageous phenotypes and were therefore positively selected and fixed in modern humans (the "less-ismore" hypothesis). Representative cases of human gene inactivation and their functional implications are presented in this review. Functional studies of additional inactive genes will provide insight into the molecular mechanisms underlying acquisition of various human-specific traits. [BMB Reports 2015; 48(7): 373-379]

• Proceedings of the Botanical Society of Korea Conference
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• 1987.07a
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• pp.349-356
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• 1987

Insertions of transposable elements in or near a structural gene give rise to null phenotypes, reduced levels of gene expression, or alteration on the tissue-specific pattern of gene expression. Null phenotypes often result from insertions in exons. Reduced levels of gene expression results from insertions in various regions such as promoter region, 5' non-translated region, exon and intron. The maize allele of Adh1-3F1124 is an example of alteration in the tissue-specific patetern of gene expression. Adh1-3F1124 contains a Mu element inserted 31 bp 5' to the transcriptional start site of the wild-type Adh1 activity in seeds and anaerobically-treated seedlings but normal levels in the pollen. Upon the insertion of a transposable element a certain number of host DNA sequences at the insertion site is duplcated. When transposable elements excise, all element sequences are deleted. However, the duplicated host sequences may be left intact or deleted to various extents. This results in null phenotypes, restoration of original levels of gene expression, or altered levels of gene expression. On the basis of effects of transposable-element insertions or excisions on gene expression, the usefulness of transposable ellements for studies on gene expression is discussed.

• YAKHAK HOEJI
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• v.41 no.4
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• pp.533-537
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• 1997

The characteristics of the resistance phenotypes of Bacillus subtilis having ermk and its terminator region mutants were determined. Wild type ermK(pEC101) and pECMT109(methylase SD-region mutant) showed typical inducible resistance phenotype. pECMF1(terminator1 region mutant) and pECMT2(terminator2 region mutant) showed constitutive resistance to Kitasamycin but inducible resistance to tylosin. In contrast, pECMT3(terminator1 and terminator2 double mutant) and pECMT309(terminator1, terminator2 and methylase SD region triple mutant) showed constitutive resistance both to kitasamycin and tylosin.

• Food Science and Industry
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• v.51 no.1
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• pp.37-44
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• 2018

The prevalence of obesity is continually increasing in South Korea; about 1/3 of adults are diagnosed with obesity and 1/2 of adults are overweight in 2016. Abnormal body fat mass increased the risk factors of metabolic syndrome (including hypertension, type II diabetes, dyslipidemia), chronic kidney failure, osteoarthritis, and cardiovascular disease. Ministry of Food and Drug Safety (MFDS) in Korea established the validation and approval system for "functional food" based on related laws and regulations. According to the guideline of MFDS, the biomarkers for obesity study in vitro, in vivo, and clinical trial are well summarized. The analysis of physical phenotypes is necessary condition to study further molecular phenotypes and pathway analysis in vivo study. Thus, we will review currently available physical phenotype analysis; dual energy X-ray absorptiometry (DEXA) and Oxylet gas analysis will be examined in-depth.