• Genomics & Informatics
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• 제11권1호
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• pp.46-51
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• 2013

Normal-karyotype acute myeloid leukemia (NK-AML) is a highly malignant and cytogenetically heterogeneous hematologic cancer. We searched for somatic mutations from 10 pairs of tumor and normal cells by using a highly efficient and reliable analysis workflow for whole-exome sequencing data and performed association tests between the NK-AML and somatic mutations. We identified 21 nonsynonymous single nucleotide variants (SNVs) located in a coding region of 18 genes. Among them, the SNVs of three leukemia-related genes (MUC4, CNTNAP2, and GNAS) reported in previous studies were replicated in this study. We conducted stepwise genetic risk score (GRS) models composed of the NK-AML susceptible variants and evaluated the prediction accuracy of each GRS model by computing the area under the receiver operating characteristic curve (AUC). The GRS model that was composed of five SNVs (rs75156964, rs56213454, rs6604516, rs10888338, and rs2443878) showed 100% prediction accuracy, and the combined effect of the three reported genes was validated in the current study (AUC, 0.98; 95% confidence interval, 0.92 to 1.00). Further study with large sample sizes is warranted to validate the combined effect of these somatic point mutations, and the discovery of novel markers may provide an opportunity to develop novel diagnostic and therapeutic targets for NK-AML.

• 생명과학회지
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• 제29권1호
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• pp.1-8
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• 2019

한우(한국 재래 소)에서 반수체형 페이징을 위한 고밀도 시퀀싱을 이용한 비교 분석 논문은 많지가 않다. 이런 고밀도 시퀀싱 플랫폼 중에서, 일루미나에서 서비스 하는 Truseq Synthetic Long-Read Haplotyping 시퀀싱 플랫폼(TSLRH)과 10X Genomics에서 서비스하는 The Chromium Genome 시퀀싱 플랫폼을 특별히 비교 분석하는 논문은 없다. 우리는 한우 연구소의 한우 종모우(아이디: TN1505D2184 or 27214)의 정액에서 DNA를 추출하였으며, 이 DNA로부터 각각의 시퀀싱 플랫폼을 이용하여 시퀀싱 데이터를 생산하였다. 그 후, 우리는 각각의 시퀀싱 플랫폼에 맞는 분석 방법을 이용하여 단일염기서열변이들은 찾아냈다. 그 결과, TSLRH과 10XG의 전체 리드 수는 각각 355,208,304, 1,632,772,004, 맵핑 리드의 개수는 351,992,768(99.09%), 1,526,641,824(93.50%), Q30(%)은 89.04%, 88.60%, 평균 밀도는 13.04X, 74.3X, 가장 긴 페이즈 블락은 1,982,706bp, 1,480,081 bp, N50 페이즈 블락은 57,637 bp, 114,394 bp, 전체 단일염기서열변이는 4,534,989, 8,496,813, 전체 페이징 비율은 72.29%, 87.67%였다. 더욱이, 우리는 각각의 시퀀싱 플랫폼을 비교해서 각각의 시퀀싱 플랫폼의 고유한 단일염기서열변이와 두 시퀀싱 플랫폼에서 공통적으로 존재하는 단일염기서열변이를 각 염색체 별로 확인하였으며, 단일염기서열변이의 개수는 염색체 길이에 정비례한다는 결과를 확인하였다. 결론적으로, 본 연구에서 추천하는 바는 연구비가 충분하지 않을 시에는 TSLRH 보다 10XG을 사용하는 것을 추천한다. 왜냐하면 전체 리드 및 단일염기서열변이 개수, N50 페이즈 블락, 가장 긴 페이즈 블락, 페이즈 비율 그리고 평균 밀도 등이 TSLRH 보다 10XG가 더 높거나 좋기 때문이다.

• Journal of Gastric Cancer
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• 제22권4호
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• pp.348-368
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• 2022

Purpose: Chromosomal instability is a hallmark of gastric cancer (GC). It can be driven by single nucleotide variants (SNVs) in cell cycle genes. We investigated the associations between SNVs in candidate genes, PLK2, PLK3, and ATM, and GC risk and clinicopathological features. Materials and Methods: The genotyping study included 542 patients with GC and healthy controls. Generalized linear models were used for the risk and clinicopathological association analyses. Survival analysis was performed using the Kaplan-Meier method. The binding of candidate miRs was analyzed using a luciferase reporter assay. Results: The PLK2 C_rs15009-C_rs963615 haplotype was under-represented in the GC group compared to that in the control group (P_corr=0.050). Male patients with the PLK2 rs963615 CT genotype had a lower risk of GC, whereas female patients had a higher risk (P=0.023; P=0.026). The PLK2 rs963615 CT genotype was associated with the absence of vascular invasion (P=0.012). The PLK3 rs12404160 AA genotype was associated with a higher risk of GC in the male population (P=0.015). The ATM T_rs228589-A_rs189037-G_rs4585 haplotype was associated with a higher risk of GC (P<0.001). The ATM rs228589, rs189037, and rs4585 genotypes TA+AA, AG+GG, and TG+GG were associated with the absence of perineural invasion (P=0.034). In vitro analysis showed that the cancer-associated miR-23b-5p mimic specifically bound to the PLK2 rs15009 G allele (P=0.0097). Moreover, low miR-23b expression predicted longer 10-year survival (P=0.0066) in patients with GC. Conclusions: PLK2, PLK3, and ATM SNVs could potentially be helpful for the prediction of GC risk and clinicopathological features. PLK2 rs15009 affects the binding of miR-23b-5p. MiR-23b-5p expression status could serve as a prognostic marker for survival in patients with GC.

• The Plant Pathology Journal
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• 제33권5호
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• pp.478-487
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• 2017

Soybean is the most important legume crop in the world. Several diseases in soybean lead to serious yield losses in major soybean-producing countries. Moreover, soybean can be infected by diverse viruses. Recently, we carried out a large-scale screening to identify viruses infecting soybean using available soybean transcriptome data. Of the screened transcriptomes, a soybean transcriptome for soybean seed development analysis contains several virus-associated sequences. In this study, we identified five viruses, including soybean mosaic virus (SMV), infecting soybean by de novo transcriptome assembly followed by blast search. We assembled a nearly complete consensus genome sequence of SMV China using transcriptome data. Based on phylogenetic analysis, the consensus genome sequence of SMV China was closely related to SMV isolates from South Korea. We examined single nucleotide variations (SNVs) for SMVs in the soybean seed transcriptome revealing 780 SNVs, which were evenly distributed on the SMV genome. Four SNVs, C-U, U-C, A-G, and G-A, were frequently identified. This result demonstrated the quasispecies variation of the SMV genome. Taken together, this study carried out bioinformatics analyses to identify viruses using soybean transcriptome data. In addition, we demonstrated the application of soybean transcriptome data for virus genome assembly and SNV analysis.

• Asian-Australasian Journal of Animal Sciences
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• 제33권5호
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• pp.712-721
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• 2020

Objective: The Wannan Black pig is a typical Chinese indigenous, disease-resistant pig breed with high fertility, and a crude-feed tolerance that has been bred by artificial selection in the south of Anhui province for a long time. However, genome variation, genetic relationships with other pig breeds, and domestication, remain poorly understood. Here, we focus on elucidating the genetic characteristics of the Wannan Black pig and identifying selection signatures during domestication and breeding. Methods: We identified the whole-genome variation in the Wannan Black pig and performed population admixture analyses to determine genetic relationships with other domesticated pig breeds and wild boars. Then, we identified the selection signatures between the Wannan Black pig and Asian wild boars in 100-kb windows sliding in 10 kb steps by using two approaches: the fixation index (F_ST) and π ratios. Results: Resequencing the Wannan Black pig genome yielded 501.52 G of raw data. After calling single-nucleotide variants (SNVs) and insertions/deletions (InDels), we identified 21,316,754 SNVs and 5,067,206 InDels (2,898,582 inserts and 2,168,624 deletions). Additionally, we found genes associated with growth, immunity, and digestive functions. Conclusion: Our findings help in explaining the unique genetic and phenotypic characteristics of Wannan Black pigs, which in turn can be informative for future breeding programs of Wannan Black pigs.

• Journal of Gastric Cancer
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• 제20권1호
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• pp.29-40
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• 2020

Purpose: Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either KIT or platelet-derived growth factor receptor A (PDGFRA) and are highly responsive to several selective tyrosine kinase inhibitors. In this study, a targeted next-generation sequencing (NGS) assay with an Oncomine Focus Assay (OFA) panel was used for the genetic characterization of molecular targets in 30 Korean patients with GIST. Materials and Methods: Using the OFA that enables rapid and simultaneous detection of hotspots, single nucleotide variants (SNVs), insertion and deletions (Indels), copy number variants (CNVs), and gene fusions across 52 genes relevant to solid tumors, targeted NGS was performed using genomic DNA extracted from formalin-fixed and paraffin-embedded samples of 30 GISTs. Results: Forty-three hotspot/other likely pathogenic variants (33 SNVs, 8 Indels, and 2 amplifications) in 16 genes were identified in 26 of the 30 GISTs. KIT variants were most frequent (44%, 19/43), followed by 6 variants in PIK3CA, 3 in PDGFRA, 2 each in JAK1 and EGFR, and 1 each in AKT1, ALK, CCND1, CTNNB1, FGFR3, FGFR4, GNA11, GNAQ, JAK3, MET, and SMO. Based on the mutation types, majority of the variants carried missense mutations (60%, 26/43), followed by 8 frameshifts, 6 nonsense, 1 stop-loss, and 2 amplifications. Conclusions: Our study confirmed the advantage of using targeted NGS with a cancer gene panel to efficiently identify mutations associated with GISTs. These findings may provide a molecular genetic basis for developing new drugs targeting these gene mutations for GIST therapy.

• Journal of Applied Biological Chemistry
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• 제63권3호
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• pp.189-195
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• 2020

The soybean (Glycine max L.), also known as the soya bean, is an economically important legume species. Pathogens are always major threats for soybean cultivation. Several pathogens negatively affect soybean production. The soybean is also known as a susceptible host to many viruses. Recently, we carried out systematic analyses to identify viruses infecting soybeans using soybean transcriptome data. Our screening results showed that only few soybean transcriptomes contained virus-associated sequences. In this study, we further carried out bioinformatics analyses using a soybean flower bud transcriptome for virus identification, genome assembly, and single nucleotide variations (SNVs). We assembled the genome of Soybean yellow common mosaic virus (SYCMV) isolate China and revealed two SNVs. Phylogenetic analyses using three viral proteins suggested that SYCMV isolate China is closely related to SYCMV isolates from South Korea. Furthermore, we found that replication and mutation of SYCMV is relatively low, which might be associated with flower bud tissue. The most interesting finding was that SYCMV was not detected in the cytoplasmic male sterility (CMS) line derived from the non-CMS line that was severely infected by SYCMV. In summary, in silico analyses identified SYCMV from the soybean flower bud transcriptome, and a nearly complete genome of SYCMV was successfully assembled. Our results suggest that the low level of virus replication and mutation for SYCMV might be associated with plant tissues. Moreover, we provide the first evidence that male sterility might be used to eliminate viruses in crop plants.