• Genomics & Informatics
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• 제15권2호
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• pp.69-80
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• 2017

In this study, cytolethal distending toxin (CDT) producer isolates genome were compared with genome of pathogenic and commensal Escherichia coli strains. Conserved genomic signatures among different types of CDT producer E. coli strains were assessed. It was shown that they could be used as biomarkers for research purposes and clinical diagnosis by polymerase chain reaction, or in vaccine development. cdt genes and several other genetic biomarkers were identified as signature sequences in CDT producer strains. The identified signatures include several individual phage proteins (holins, nucleases, and terminases, and transferases) and multiple members of different protein families (the lambda family, phage-integrase family, phage-tail tape protein family, putative membrane proteins, regulatory proteins, restriction-modification system proteins, tail fiber-assembly proteins, base plate-assembly proteins, and other prophage tail-related proteins). In this study, a sporadic phylogenic pattern was demonstrated in the CDT-producing strains. In conclusion, conserved signature proteins in a wide range of pathogenic bacterial strains can potentially be used in modern vaccine-design strategies.

• Genomics & Informatics
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• 제19권4호
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• pp.40.1-40.11
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• 2021

Mutation signatures represent unique sequence footprints of somatic mutations resulting from specific DNA mutagenic and repair processes. However, their causal associations and the potential utility for genome research remain largely unknown. In this study, we performed PanCancer-scale correlative analyses to identify the genomic features associated with tumor mutation burdens (TMB) and individual mutation signatures. We observed that TMB was correlated with tumor purity, ploidy, and the level of aneuploidy, as well as with the expression of cell proliferation-related genes representing genomic covariates in evaluating TMB. Correlative analyses of mutation signature levels with genes belonging to specific DNA damage-repair processes revealed that deficiencies of NHEJ1 and ALKBH3 may contribute to mutations in the settings of APOBEC cytidine deaminase activation and DNA mismatch repair deficiency, respectively. We further employed a strategy to identify feature-driven, de novo mutation signatures and demonstrated that mutation signatures can be reconstructed using known causal features. Using the strategy, we further identified tumor hypoxia-related mutation signatures similar to the APOBEC-related mutation signatures, suggesting that APOBEC activity mediates hypoxia-related mutational consequences in cancer genomes. Our study advances the mechanistic insights into the TMB and signature-based DNA mutagenic and repair processes in cancer genomes. We also propose that feature-driven mutation signature analysis can further extend the categories of cancer-relevant mutation signatures and their causal relationships.

• 정보처리학회논문지A
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• 제8A권4호
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• pp.509-516
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• 2001

생명 과학의 발전과 많은 게놈(genome) 프로젝트의 결과로 여러 종의 게놈 서열이 밝혀지고 있다. 생물체의 서열을 분석하는 방법은 전역정렬(global alignment), 지역정렬(local alignment) 등 여러 가지 방법이 있는데, 그 중 하나가 k-mer 분석이다. k-mer는 유전자의 염기 서열내의 길이가 k인 연속된 염기 서열로서 k-mer 분석은 염기서열이 가진 k-mer들의 빈도 분포나 대칭성 등을 탐색하는 것이다. 그런데 게놈의 염기 서열은 대용량 텍스트이고 k가 클 때 기존의 온메모리 알고리즘으로는 처리가 불가능하므로 효율적인 자료구조와 알고리즘이 필요하다. 스트링 B-트리는 패턴 일치(pattern matching)에 적합하고 외부 메모리를 지원하는 좋은 자료구조이다. 본 논문에서는 스트링 B-트리(string B-tree)를 k-mer 분석에 효율적인 구조로 개선하여, C. elegans 외의 30개의 게놈 서열에 대해 분석한다. k-mer들의 빈도 분포와 대칭성을 보여주기 위해 CGR(Chaotic Game Representation)을 이용한 가시화 시스템을 제시한다. 게놈 서열과 매우 유사한 서열 상의 어떤 부분을 시그니쳐(signature)라 하고, 높은 유사도를 가지는 최소 길이의 시그니쳐를 찾는 알고리즘을 제시한다.

• Molecules and Cells
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• 제39권2호
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• pp.77-86
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• 2016

Cancer is a heterogeneous disease caused by diverse genomic alterations in oncogenes and tumor suppressor genes. Despite recent advances in high-throughput sequencing technologies and development of targeted therapies, novel cancer drug development is limited due to the high attrition rate from clinical studies. Patient-derived xenografts (PDX), which are established by the transfer of patient tumors into immunodeficient mice, serve as a platform for co-clinical trials by enabling the integration of clinical data, genomic profiles, and drug responsiveness data to determine precisely targeted therapies. PDX models retain many of the key characteristics of patients' tumors including histology, genomic signature, cellular heterogeneity, and drug responsiveness. These models can also be applied to the development of biomarkers for drug responsiveness and personalized drug selection. This review summarizes our current knowledge of this field, including methodologic aspects, applications in drug development, challenges and limitations, and utilization for precision cancer medicine.

• Animal Bioscience
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• 제37권3호
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• pp.461-470
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• 2024

Objective: The objective of this study was to investigate the genetic diversity, population structure and whole-genome selection signatures of Luxi cattle to reveal its genomic characteristics in terms of meat and carcass traits, skeletal muscle development, body size, and other traits. Methods: To further analyze the genomic characteristics of Luxi cattle, this study sequenced the whole-genome of 16 individuals from the core conservation farm in Shandong region, and collected 174 published genomes of cattle for conjoint analysis. Furthermore, three different statistics (pi, F_st, and XP-EHH) were used to detect potential positive selection signatures related to selection in Luxi cattle. Moreover, gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analyses were performed to reveal the potential biological function of candidate genes harbored in selected regions. Results: The results showed that Luxi cattle had high genomic diversity and low inbreeding levels. Using three complementary methods (pi, F_st, and XP-EHH) to detect the signatures of selection in the Luxi cattle genome, there were 2,941, 2,221 and 1,304 potentially selected genes identified, respectively. Furthermore, there were 45 genes annotated in common overlapping genomic regions covered 0.723 Mb, including PLAG1 zinc finger (PLAG1), dedicator of cytokinesis 3 (DOCK3), ephrin A2 (EFNA2), DAZ associated protein 1 (DAZAP1), Ral GTPase activating protein catalytic subunit alpha 1 (RALGAPA1), mediator complex subunit 13 (MED13), and decaprenyl diphosphate synthase subunit 2 (PDSS2), most of which were enriched in pathways related to muscle growth and differentiation and immunity. Conclusion: In this study, we provided a series of genes associated with important economic traits were found in positive selection regions, and a scientific basis for the scientific conservation and genetic improvement of Luxi cattle.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.7.1-7.12
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• 2018

Recent findings from The Cancer Genome Atlas project have provided a comprehensive map of genomic alterations that occur in hepatocellular carcinoma (HCC), including unexpected mutations in apolipoprotein B (APOB). We aimed to determine the clinical significance of this non-oncogenetic mutation in HCC. An Apob gene signature was derived from genes that differed between control mice and mice treated with siRNA specific for Apob (1.5-fold difference; P < 0.005). Human gene expression data were collected from four independent HCC cohorts (n = 941). A prediction model was constructed using Bayesian compound covariate prediction, and the robustness of the APOB gene signature was validated in HCC cohorts. The correlation of the APOB signature with previously validated gene signatures was performed, and network analysis was conducted using ingenuity pathway analysis. APOB inactivation was associated with poor prognosis when the APOB gene signature was applied in all human HCC cohorts. Poor prognosis with APOB inactivation was consistently observed through cross-validation with previously reported gene signatures (NCIP A, HS, high-recurrence SNUR, and high RS subtypes). Knowledge-based gene network analysis using genes that differed between low-APOB and high-APOB groups in all four cohorts revealed that low-APOB activity was associated with upregulation of oncogenic and metastatic regulators, such as HGF, MTIF, ERBB2, FOXM1, and CD44, and inhibition of tumor suppressors, such as TP53 and PTEN. In conclusion, APOB inactivation is associated with poor outcome in patients with HCC, and APOB may play a role in regulating multiple genes involved in HCC development.

• Asian-Australasian Journal of Animal Sciences
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• 제32권8호
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• pp.1069-1076
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• 2019

Objective: Yunnan is not only a frontier zone that connects China with South and Southeast Asia, but also represents an admixture zone between taurine (Bos taurus) and zebu (Bos indicus) cattle. The purpose of this study is to understand the level of genomic diversity and the extent of admixture in each Yunnan native cattle breed. Methods: All 120 individuals were genotyped using Illumina BovineHD BeadChip (777,962 single nucleotide polymorphisms [SNPs]). Quality control and genomic diversity indexes were calculated using PLINK software. The principal component analysis (PCA) was assessed using SMARTPCA program implemented in EIGENSOFT software. The ADMIXTURE software was used to reveal admixture patterns among breeds. Results: A total of 604,630 SNPs was obtained after quality control procedures. Among six breeds, the highest level of mean heterozygosity was found in Zhaotong cattle from Northeastern Yunnan, whereas the lowest level of heterozygosity was detected in Dehong humped cattle from Western Yunnan. The PCA based on a pruned dataset of 233,788 SNPs clearly separated Dehong humped cattle (supposed to be a pure zebu breed) from other five breeds. The admixture analysis further revealed two clusters (K = 2 with the lowest cross validation error), corresponding to taurine and zebu cattle lineages. All six breeds except for Dehong humped cattle showed different degrees of admixture between taurine and zebu cattle. As expected, Dehong humped cattle showed no signature of taurine cattle influence. Conclusion: Overall, considerable genomic diversity was found in six Yunnan native cattle breeds except for Dehong humped cattle from Western Yunnan. Dehong humped cattle is a pure zebu breed, while other five breeds had admixed origins with different extents of admixture between taurine and zebu cattle. Such admixture by crossbreeding between zebu and taurine cattle facilitated the spread of zebu cattle from tropical and subtropical regions to other highland regions in Yunnan.

• 한국어병학회지
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• 제28권2호
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• pp.99-107
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• 2015

Despite its economic importance as an aquaculture species, the molecular and genetic information regarding physiologically important elements in rock bream (Oplegnathus fasciatus) is not completely understood. Rab proteins play a vital role in cellular mechanisms and immunity as one of the key regulators of membrane trafficking. In this investigation, a Rab gene, named as RbRab-5C-like, was identified from Oplegnathus fasciatus. RbRab-5C-like protein exhibited high homology with Rab proteins of other species and possessed signature characteristics of Rab proteins with four conserved cysteine residues. Phylogenetic analysis showed that RbRab-5C-like clustered with other fish counterparts. The RbRab-5C-like genomic sequence possesses six exons and five introns. Transcriptional analysis revealed that RbRab-5C-like was ubiquitously expressed in all examined tissues with the highest expression occurring in the liver. While the structural and homologic characteristics of RbRab-5C-like suggest a strong conservation of this element in different species, its mRNA distribution implies a wide range of biological significance in rock bream.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.185-190
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• 2014

Influence of loneliness on human survival has been established epidemiologically, but genomic research remains undeveloped. We identified 34 loneliness-associated genes which were statistically significant for high-lonely and low-lonely individuals. With the univariate Cox proportional hazards regression model, we obtained corresponding regression coefficients for loneliness-associated genes fo individual cancer patients. Furthermore, risk scores could be generated with the combination of gene expression level multiplied by corresponding regression coefficients of loneliness-associated genes. We verified that high-risk score cancer patients had shorter mean survival time than their low-risk score counterparts. Then we validated the loneliness-associated gene signature in three independent brain cancer cohorts with Kaplan-Meier survival curves (n=77, 85 and 191), significantly separable by log-rank test with hazard ratios (HR) >1 and p-values <0.0001 (HR=2.94, 3.82, and 1.78). Moreover, we validated the loneliness-associated gene signature in bone cancer (HR=5.10, p-value=4.69e-3), lung cancer (HR=2.86, p-value=4.71e-5), ovarian cancer (HR=1.97, p-value=3.11e-5), and leukemia (HR=2.06, p-value=1.79e-4) cohorts. The last lymphoma cohort proved to have an HR=3.50, p-value=1.15e-7. Loneliness-associated genes had good survival prediction for cancer patients, especially bone cancer patients. Our study provided the first indication that expression of loneliness-associated genes are related to survival time of cancer patients.

• Journal of Animal Science and Technology
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• 제56권7호
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• pp.23.1-23.7
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• 2014

Background: Scanning of the genome for selection signatures between breeds may play important role in understanding the underlie causes for observable phenotypic variations. The discovery of high density single nucleotide polymorphisms (SNPs) provide a useful starting point to perform genome-wide scan in pig populations in order to identify loci/candidate genes underlie phenotypic variation in pig breeds and facilitate genetic improvement programs. However, prior to this study genomic region under selection in commercially selected Berkshire and Korean native pig breeds has never been detected using high density SNP markers. To this end, we have genotyped 45 animals using Porcine SNP60 chip to detect selection signatures in the genome of the two breeds by using the $F_{ST}$ approach. Results: In the comparison of Berkshire and KNP breeds using the FDIST approach, a total of 1108 outlier loci (3.48%) were significantly different from zero at 99% confidence level with 870 of the outlier SNPs displaying high level of genetic differentiation ($F_{ST}{\geq}0.490$). The identified candidate genes were involved in a wide array of biological processes and molecular functions. Results revealed that 19 candidate genes were enriched in phosphate metabolism (GO: 0006796; ADCK1, ACYP1, CAMK2D, CDK13, CDK13, ERN1, GALK2, INPP1; MAK, MAP2K5, MAP3K1, MAPK14, P14KB, PIK3C3, PRKC1, PTPRK, RNASEL, THBS1, BRAF, VRK1). We have identified a set of candidate genes under selection and have known to be involved in growth, size and pork quality (CART, AGL, CF7L2, MAP2K5, DLK1, GLI3, CA3 and MC3R), ear morphology and size (HMGA2 and SOX5) stress response (ATF2, MSRB3, TMTC3 and SCAF8) and immune response (HCST and RYR1). Conclusions: Some of the genes may be used to facilitate genetic improvement programs. Our results also provide insights for better understanding of the process and influence of breed development on the pattern of genetic variations.