• Title/Summary/Keyword: Gene Prediction

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Bayesian Survival Analysis of High-Dimensional Microarray Data for Mantle Cell Lymphoma Patients

  • Moslemi, Azam;Mahjub, Hossein;Saidijam, Massoud;Poorolajal, Jalal;Soltanian, Ali Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.95-100
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    • 2016
  • Background: Survival time of lymphoma patients can be estimated with the help of microarray technology. In this study, with the use of iterative Bayesian Model Averaging (BMA) method, survival time of Mantle Cell Lymphoma patients (MCL) was estimated and in reference to the findings, patients were divided into two high-risk and low-risk groups. Materials and Methods: In this study, gene expression data of MCL patients were used in order to select a subset of genes for survival analysis with microarray data, using the iterative BMA method. To evaluate the performance of the method, patients were divided into high-risk and low-risk based on their scores. Performance prediction was investigated using the log-rank test. The bioconductor package "iterativeBMAsurv" was applied with R statistical software for classification and survival analysis. Results: In this study, 25 genes associated with survival for MCL patients were identified across 132 selected models. The maximum likelihood estimate coefficients of the selected genes and the posterior probabilities of the selected models were obtained from training data. Using this method, patients could be separated into high-risk and low-risk groups with high significance (p<0.001). Conclusions: The iterative BMA algorithm has high precision and ability for survival analysis. This method is capable of identifying a few predictive variables associated with survival, among many variables in a set of microarray data. Therefore, it can be used as a low-cost diagnostic tool in clinical research.

CYP3A4 Expression in Breast Cancer and its Association with Risk Factors in Mexican Women

  • Floriano-Sanchez, Esau;Rodriguez, Noemi Cardenas;Bandala, Cindy;Coballase-Urrutia, Elvia;Lopez-Cruz, Jaime
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3805-3809
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    • 2014
  • Background: In Mexico, breast cancer (BCa) is the leading type of cancer in women. Cytochrome P450 (CYP450) is a superfamily of major oxidative enzymes that metabolize carcinogens and many antineoplastic drugs. In addition, these enzymes have influence on tumor development and tumor response to therapy. In this report, we analyzed the protein expression in patients with BCa and in healthy women. Links with some clinic-pathological characteristic were also assessed. Materials and Methods: Immunohistochemical analyses were conducted on 48 sets of human breast tumors and normal breast tissues enrolled in Hospital Militar de Especialidades de la Mujer y Neonatologia and Hospital Central Militar, respectively, during the time period from 2010 to 2011. Informed consent was obtained from all participants. Statistical analysis was performed using ${\chi}^2$ or Fisher exact tests to estimate associations and the Mann Whitney U test for comparison of group means. Results: We found a significant CYP3A4 overexpression in BCa stroma and gland regions in comparison with healthy tissue. A significant association between protein expression with smoking, alcoholism and hormonal contraceptives use was also observed. Additionally, we observed estrogen receptor (ER) and progesterone receptor (PR) positive association in BCa. Conclusions: We suggest that CYP3A4 expression promotes BCa development and can be used in the prediction of tumor response to different treatments. One therapeutic approach may thus be to block CYP3A4 function.

Construction of a Protein-Protein Interaction Network for Chronic Myelocytic Leukemia and Pathway Prediction of Molecular Complexes

  • Zhou, Chao;Teng, Wen-Jing;Yang, Jing;Hu, Zhen-Bo;Wang, Cong-Cong;Qin, Bao-Ning;Lv, Qing-Liang;Liu, Ze-Wang;Sun, Chang-Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5325-5330
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    • 2014
  • Background: Chronic myelocytic leukemia is a disease that threatens both adults and children. Great progress has been achieved in treatment but protein-protein interaction networks underlining chronic myelocytic leukemia are less known. Objective: To develop a protein-protein interaction network for chronic myelocytic leukemia based on gene expression and to predict biological pathways underlying molecular complexes in the network. Materials and Methods: Genes involved in chronic myelocytic leukemia were selected from OMIM database. Literature mining was performed by Agilent Literature Search plugin and a protein-protein interaction network of chronic myelocytic leukemia was established by Cytoscape. The molecular complexes in the network were detected by Clusterviz plugin and pathway enrichment of molecular complexes were performed by DAVID online. Results and Discussion: There are seventy-nine chronic myelocytic leukemia genes in the Mendelian Inheritance In Man Database. The protein-protein interaction network of chronic myelocytic leukemia contained 638 nodes, 1830 edges and perhaps 5 molecular complexes. Among them, complex 1 is involved in pathways that are related to cytokine secretion, cytokine-receptor binding, cytokine receptor signaling, while complex 3 is related to biological behavior of tumors which can provide the bioinformatic foundation for further understanding the mechanisms of chronic myelocytic leukemia.

MicroRNA-27 Promotes Odontoblast Differentiation via Wnt1 Signaling

  • Cho, Ji-Ho;Kim, Su-Gwan;Park, Byung-Sun;Go, Dae-San;Park, Joo-Cheol;Kim, Do Kyung
    • International Journal of Oral Biology
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    • v.40 no.4
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    • pp.197-204
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    • 2015
  • MicroRNA (miRNA, miR) is essential in regulating cell differentiation either by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNA in odontoblastic cell differentiation is still unclear. In this study, we examined the molecular mechanism of miR-27-mediated regulation of odontoblast differentiation in MDPC-23 mouse odontoblastic cells derived from mouse dental papilla cells. The results of the present study demonstrated that the miR-27 expression increases significantly during MDPC-23 odontoblastic cell differentiation. Furthermore, miR-27 up-regulation promotes the differentiation of MDPC-23 cells and accelerates mineralization without cell proliferation. The over-expression of miR-27 significantly increased the expression levels of Wnt1 mRNA and protein. In addition, the results of target gene prediction revealed that Wnt1 mRNA has an miR-27 binding site in its 3'UTR, and is increased by miR-27. These results suggested that miR-27 promotes MDPC-23 odontoblastic cell differentiation by targeting Wnt1 signaling. Therefore, miR-27 is a critical odontoblastic differentiation molecular target for the development of miRNA based therapeutic agents in dental medicine.

Water Quality Management using WASPS & WASP Builder for a Basin of an Agricultural Reservoir (WASP5 & WASP Builder을 이용한 농업용저수지 유역의 수질관리)

  • Chung, Paul-Gene;Goh, Hong-Seok;Hyun, Mi-Hee;Lee, Eun-Ju
    • Journal of Korean Society on Water Environment
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    • v.20 no.5
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    • pp.422-431
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    • 2004
  • Water quality modeling was performed for the purpose of diagnosis and prediction of water quality in Gyoung Choen reservoir, using EUTR05/WASP Build model. WASP Builder is capable of visual display in window and it has an advantage of updating and modification for data. Field data of 1992, Spring, Summer, and Fall, were used to calibrate model and these results were validated using data of 2000, Spring, Summer, and Fall. The reservoir was divided into 4 epilimnion segments. Water quality system for modeling were consist of BOD, Chlorophyll-a, DO, $NH_3-N$, $NO_3-N$, T-N, $PO_4-P$, T-P. The results of water quality modelling using EUTR05/WASP Builder, a range of the Correlation for calibration of BOD, T-N, T-P, and Chlorophyll-a according to three seasons are 0.63~0.90, 0.81~0.97, 0.75~0.98, and 0.77~0.98 respectively. And the correlation between simulated and observed values for verification of BOD, T-N, T-P, and Chlorophyll-a according to three seasons are 0.93, 0.94, 0.81, and 0.80 respectively. Among the pollutant sources for a basin of the Gyoung Choen reservoir, generated amount of livestock is the highest and BOD, T-N, T-P of generated loading percentage are 94%, 81%, and 95%. So, we suppose that inflow load amount will decrease 50% and increase 50% only livestock about current load amount. If increasing load amount of livestock 50% in segment 2 and 3, BOD, T-N, and T-P simulated increasing to range of $0.02~0.15mg/{\ell}$, $0.029~0.08mg/{\ell}$, $0.011~0.029mg/{\ell}$ in comparison with current water quality

Prediction of Genes Related to Positive Selection Using Whole-Genome Resequencing in Three Commercial Pig Breeds

  • Kim, HyoYoung;Caetano-Anolles, Kelsey;Seo, Minseok;Kwon, Young-jun;Cho, Seoae;Seo, Kangseok;Kim, Heebal
    • Genomics & Informatics
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    • v.13 no.4
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    • pp.137-145
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    • 2015
  • Selective sweep can cause genetic differentiation across populations, which allows for the identification of possible causative regions/genes underlying important traits. The pig has experienced a long history of allele frequency changes through artificial selection in the domestication process. We obtained an average of 329,482,871 sequence reads for 24 pigs from three pig breeds: Yorkshire (n = 5), Landrace (n = 13), and Duroc (n = 6). An average read depth of 11.7 was obtained using whole-genome resequencing on an Illumina HiSeq2000 platform. In this study, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio tests were implemented to detect genes experiencing positive selection for the genome-wide resequencing data generated from three commercial pig breeds. In our results, 26, 7, and 14 genes from Yorkshire, Landrace, and Duroc, respectively were detected by two kinds of statistical tests. Significant evidence for positive selection was identified on genes ST6GALNAC2 and EPHX1 in Yorkshire, PARK2 in Landrace, and BMP6, SLA-DQA1, and PRKG1 in Duroc. These genes are reportedly relevant to lactation, reproduction, meat quality, and growth traits. To understand how these single nucleotide polymorphisms (SNPs) related positive selection affect protein function, we analyzed the effect of non-synonymous SNPs. Three SNPs (rs324509622, rs80931851, and rs80937718) in the SLA-DQA1 gene were significant in the enrichment tests, indicating strong evidence for positive selection in Duroc. Our analyses identified genes under positive selection for lactation, reproduction, and meat-quality and growth traits in Yorkshire, Landrace, and Duroc, respectively.

Complete Mitochondrial Genome of Crangon hakodatei (Rathbun, 1902) (Crustacea: Decapoda: Crangonidae) (마루자주새우[Crangon hakodatei (Rathbun, 1902)]의 전장 미토콘드리아 유전체에 대한 분석 연구)

  • Kim, Gyungryul;Kim, Hyun-Woo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.49 no.6
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    • pp.867-874
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    • 2016
  • Although shrimps belonging to family Crangonidae are known to be genetically divergent and ecologically important among the various benthos, any of their mitochondrial genome has not been reported yet. We here determined the complete mitochondrial genome sequence of Crangon hakodatei (Rathbun, 1902), which was collected from East China Sea ($124^{\circ}E$ and $34.5^{\circ}N$). Total mitochondrial genome length of C. hakodatei was 16,060 bp, in which 13 proteins, 2 ribosomal RNAs, 22 transfer RNAs and a putative control region were encoded. Secondary structure prediction analysis showed that twenty tRNA genes exhibit the conserved structure but two genes, $tRNA^{Cys}$ and $tRNA^{Ser}$ (AGN), lack T and D arm, respectively. Based on the sequence similarity of the COI region from the currently reported five species belonging to genus Crangonidae, C. hakodatei was most closely related to Crangon crangon. Phylogenetic analysis of full COXI genes belonging to infraorder Caridea showed that only crangonid shrimps were clustered together with those of Dendrobranchiata. Gene order were well conserved from Penaeoidea to Caridea but $tRNA^{Pro}$ and $tRNA^{Thr}$ in Palaemonid shrimp were flipped each other by the recombination. Further study about mitochondrial genome sequences of shrimps belonging to Crangonidae should be made to know better about their evolutional relationships with other those in infraorder Caridea.

The Role of MicroRNAs in Regulatory T Cells and in the Immune Response

  • Ha, Tai-You
    • IMMUNE NETWORK
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    • v.11 no.1
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    • pp.11-41
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    • 2011
  • The discovery of microRNA (miRNA) is one of the major scientific breakthroughs in recent years and has revolutionized current cell biology and medical science. miRNAs are small (19~25nt) noncoding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region (3'UTR) of specific messenger RNAs (mRNAs) for degradation of translation repression. Genetic ablation of the miRNA machinery, as well as loss or degradation of certain individual miRNAs, severely compromises immune development and response, and can lead to immune disorders. Several sophisticated regulatory mechanisms are used to maintain immune homeostasis. Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. Recent publications have provided compelling evidence that miRNAs are highly expressed in Treg cells, that the expression of Foxp3 is controlled by miRNAs and that a range of miRNAs are involved in the regulation of immunity. A large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, cardiovascular disease and diabetes, as well as psychiatric and neurological diseases. Although it is still unclear how miRNA controls Treg cell development and function, recent studies certainly indicate that this topic will be the subject of further research. The specific circulating miRNA species may also be useful for the diagnosis, classification, prognosis of diseases and prediction of the therapeutic response. An explosive literature has focussed on the role of miRNA. In this review, I briefly summarize the current studies about the role of miRNAs in Treg cells and in the regulation of the innate and adaptive immune response. I also review the explosive current studies about clinical application of miRNA.

Prediction of Residual Stress Caused by IML Process and Deformation Due to Thermal Impact (IML 성형과정에 따른 잔류응력 및 열 충격에 의한 변형 예측)

  • Lee, Jae-Won;Jang, Eu-Gene;Shin, Seung-Won;Park, Seung-Ho;Chung, Ha-Seung
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.34 no.3
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    • pp.375-382
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    • 2010
  • In this study, we developed a method to predict the residual stress distribution and thermal deformation caused by in-mold labeling (IML) processes. IML is one of the injection molding processes for injecting a material into a cavity and subsequently inserting a decorated film. The IML process can yield products with decorations of outstanding excellent quality in only one working step. Although the IML process has various advantages, it causes defects such as film delamination, wash-out, and flow marks. In particular, deformation is considered to be a major concern in terms of delamination. To validate the model, the deformation predicted by using a numerical model was compared with experimental results, and both results showed good agreement. We verified that the developed method can be used to obtain the design guidelines for preventing delamination in the initial design stage of the IML process.

Global and Local Competition between Exogenously Introduced microRNAs and Endogenously Expressed microRNAs

  • Kim, Doyeon;Kim, Jongkyu;Baek, Daehyun
    • Molecules and Cells
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    • v.37 no.5
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    • pp.412-417
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    • 2014
  • It has been reported that exogenously introduced micro-RNA (exo-miRNA) competes with endogenously expressed miRNAs (endo-miRNAs) in human cells, resulting in a detectable upregulation of mRNAs with endo-miRNA target sites (TSs). However, the detailed mechanisms of the competition between exo- and endo-miRNAs remain uninvestigated. In this study, using 74 microarrays that monitored the whole-transcriptome response after introducing miRNAs or siRNAs into HeLa cells, we systematically examined the derepression of mRNAs with exo- and/or endo-miRNA TSs. We quantitatively assessed the effect of the number of endo-miRNA TSs on the degree of mRNA derepression. As a result, we observed that the number of endo-miRNA TSs was significantly associated with the degree of derepression, supporting that the derepression resulted from the competition between exo- and endo-miRNAs. However, when we examined whether the site proficiency of exo-miRNA TSs could also influence mRNA derepression, to our surprise, we discovered a strong positive correlation. Our analysis indicates that site proficiencies of both exo- and endo-miRNA TSs are important determinants for the degree of mRNA derepression, implying that the derepression of mRNAs in response to exo-miRNA is more complex than that currently perceived. Our observations may lead to a more complete understanding of the detailed mechanisms of the competition between exo- and endo-miRNAs and to a more accurate prediction of miRNA targets. Our analysis also suggests an interesting hypothesis that long 3'-UTRs may function as molecular buffer against gene expression regulation by individual miRNAs.