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Genome-wide association studies: inherent limitations and future challenges

null

《医学前沿(英文)》 2012年 第6卷 第4期   页码 444-450 doi: 10.1007/s11684-012-0225-3

摘要:

Genome-wide association studies (GWAS) have achieved great success in identifying genetic variants related to complex human diseases such as cancer and have provided valuable insights into their genetic architecture. Recently, GWAS is quite the fashion in China. However, there are issues related to its nature. Enormous work needs to be done in the post-GWAS era. Deep sequencing followed by functional studies will be needed to elucidate the underpinning biological mechanisms and further translate GWAS findings into medical practice. Along with pharmacogenomics, the success of GWAS in identifying genetic risk factors and genetic differences in drug response has been gradually enabling personalized medicine. In this article, we used hepatocellular carcinoma (HCC) as an example to demonstrate some of the inherent limitations and summarized future challenges of GWAS.

关键词: genome-wide association studies (GWAS)     genetic variant     cancer     limitation     challenge    

Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies

null

《医学前沿(英文)》 2015年 第9卷 第2期   页码 146-161 doi: 10.1007/s11684-014-0373-8

摘要:

Obesity prevalence has increased in recent years. Lifestyle change fuels obesity, but genetic factors cause more than 50% of average variations in obesity. The advent of genome-wide association studies (GWAS) has hastened the progress of polygenic obesity research. As of this writing, more than 73 obesity susceptibility loci have been identified in ethnic groups through GWAS. The identified loci explain only 2% to 4% of obesity heritability, thereby indicating that a large proportion of loci remain undiscovered. Thus, the next step is to identify and confirm novel loci, which may exhibit smaller effects and lower allele frequencies than established loci. However, achieving these tasks has been difficult for researchers. GWAS help researchers discover the causal loci. Moreover, numerous biological studies have been performed on the polygenic effects on obesity, such as studies on fat mass- and obesity-associated gene (FTO), but the role of these polygenic effects in the mechanism of obesity remains unclear. Thus, obesity-causing variations should be identified, and insights into the biology of polygenic effects on obesity are needed.

关键词: obesity     genetics     genome-wide association studies     body mass index     fat mass- and obesity-associated gene    

A genome-wide association study of five meat quality traits in Yorkshire pigs

Qian DONG,Huiying LIU,Xinyun LI,Wei WEI,Shuhong ZHAO,Jianhua CAO

《农业科学与工程前沿(英文)》 2014年 第1卷 第2期   页码 137-143 doi: 10.15302/J-FASE-2014014

摘要: Meat quality is an important trait in the pig industry. To identify genomic regions and haplotype blocks responsible for meat quality traits in pigs, a genome-wide association study was conducted for five traits including intramuscular fat content, pH at 45 min and 24 h, drip loss within 24 h and water-holding capacity in 231 Yorkshire barrows using illumina porcine 60k SNP chips. The results showed that a total of 344 single nucleotide polymorphisms (SNP) were significantly associated with five meat quality traits ( <1×10 ). Moreover, 323 SNPs were within the reported QTL regions, of which 21 were novel. Also, 158 SNPs fell into the proximal region of meat quality related genes. In addition, 25 haplotype blocks based on 116 SNPs were revealed with SNP combination patterns for five traits. Our study added new SNP information for identification of meat quality traits in pigs and will help elucidate the mechanisms of meat quality in pigs.

关键词: Pig     GWAS     meat quality trait     SNP    

Genome-wide association study of the backfat thickness trait in two pig populations

Dandan ZHU,Xiaolei LIU,Rothschild MAX,Zhiwu ZHANG,Shuhong ZHAO,Bin FAN

《农业科学与工程前沿(英文)》 2014年 第1卷 第2期   页码 91-95 doi: 10.15302/J-FASE-2014005

摘要: Backfat thickness is a good predictor of carcass lean content, an economically important trait, and a main breeding target in pig improvement. In this study, the candidate genes and genomic regions associated with the tenth rib backfat thickness trait were identified in two independent pig populations, using a genome-wide association study of porcine 60K SNP genotype data applying the compressed mixed linear model (CMLM) statistical method. For each population, 30 most significant single-nucleotide polymorphisms (SNPs) were selected and SNP annotation implemented using Build 10.2. In the first population, 25 significant SNPs were distributed on seven chromosomes, and SNPs on SSC1 and SSC7 showed great significance for fat deposition. The most significant SNP (ALGA0006623) was located on SSC1, upstream of the gene. In the second population, 27 significant SNPs were recognized by annotation, and 12 SNPs on SSC12 were related to fat deposition. Two haplotype blocks, M1GA0016251-MARC0075799 and ALGA0065251-MARC0014203-M1GA0016298-ALGA0065308, were detected in significant regions where the and genes were identified as contributing to fat metabolism. The results indicated that genetic mechanism regulating backfat thickness is complex, and that genome-wide associations can be affected by populations with different genetic backgrounds.

关键词: backfat thickness     SNP chip     genome-wide association study     compressed mixed linear model     pig    

Genome-wide association analysis reveals genetic loci and candidate genes associated with intramuscular

Xingwang WANG, Rongrong DING, Jianping QUAN, Linxue YANG, Ming YANG, Enqin ZHENG, Dewu LIU, Gengyuan CAI, Zhenfang WU, Jie YANG

《农业科学与工程前沿(英文)》 2017年 第4卷 第3期   页码 335-341 doi: 10.15302/J-FASE-2017152

摘要: Intramuscular fat (IMF) is a major meat-quality trait in pigs. The content of IMF is directly associated with the taste and flavor of pork. As a complex trait, there could be multiple genes affecting IMF content in pork. Genome-wide association study is a powerful tool to detect genomic regions associated with phenotypic variations. The objectives of the present study were to identify or refine the positions of genomic regions affecting IMF, and to characterize candidate genes and pathways that may influence this trait. Of note, we identified a significant region in longissium dorsi muscle in a Duroc pig population for IMF content with PorcineSNP60 v2 BeadChip. This region spans 1.24 Mb on chromosome 8 and had been identified as a quantitative trait locus for IMF in Pietrain, Large White, Landrace, and Leicoma pigs. In this region, eight SNPs were significantly associated with IMF content. Three genes proximal to these significant SNPs were considered candidate genes, including , and . Our results confirm several previous findings and highlight several genes that may contribute to IMF variation in Duroc pigs.

关键词: Duroc pigs     genome-wide association analysis     intramuscular fat    

近十二年人类蛋白质N-糖基化的全基因组关联研究综述 Review

Anna Timoshchuk, Sodbo Sharapov, Yurii S. Aulchenko

《工程(英文)》 2023年 第26卷 第7期   页码 17-31 doi: 10.1016/j.eng.2023.03.013

摘要: 接下来,在第3节中,总结、分类并归纳了当前N-糖基化全基因组关联研究(GWAS)的结果,这些研究提供了有关糖基化群体变异遗传调控的新知识。

关键词: 糖组学     聚糖     N-糖基化     基因组学     遗传学     全基因组关联研究    

Systems understanding of plant–pathogen interactions through genome-wide protein–protein interaction

Hong LI,Ziding ZHANG

《农业科学与工程前沿(英文)》 2016年 第3卷 第2期   页码 102-112 doi: 10.15302/J-FASE-2016100

摘要: Plants are frequently affected by pathogen infections. To effectively defend against such infections, two major modes of innate immunity have evolved in plants; pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity. Although the molecular components as well as the corresponding pathways involved in these two processes have been identified, many aspects of the molecular mechanisms of the plant immune system remain elusive. Recently, the rapid development of omics techniques (e.g., genomics, proteomics and transcriptomics) has provided a great opportunity to explore plant–pathogen interactions from a systems perspective and studies on protein–protein interactions (PPIs) between plants and pathogens have been carried out and characterized at the network level. In this review, we introduce experimental and computational identification methods of PPIs, popular PPI network analysis approaches, and existing bioinformatics resources/tools related to PPIs. Then, we focus on reviewing the progress in genome-wide PPI networks related to plant–pathogen interactions, including pathogen-centric PPI networks, plant-centric PPI networks and interspecies PPI networks between plants and pathogens. We anticipate genome-wide PPI network analysis will provide a clearer understanding of plant–pathogen interactions and will offer some new opportunities for crop protection and improvement.

关键词: plant–pathogen interactions     systems biology     omics     plant immunity     protein–protein interaction     network    

Transcriptome resources and genome-wide marker development for Japanese larch (

Wanfeng LI,Suying HAN,Liwang QI,Shougong ZHANG

《农业科学与工程前沿(英文)》 2014年 第1卷 第1期   页码 77-84 doi: 10.15302/J-FASE-2014010

摘要: While the differential responses of trees to changes in climatic and environmental conditions have been demonstrated as they age, the underlying mechanisms and age control of tree growth and development are complex and poorly understood particularly at a molecular level. In this paper, we present a transcriptome analysis of , a deciduous conifer that is widely-grown in the northern hemisphere and of significant ecological and economic value. Using high-throughput RNA sequencing, we obtained about 26 million reads from the stems of 1-, 2-, 5-, 10-, 25- and 50-year-old trees. Combining these with the published Roche 454 sequencing reads and the expressed sequence tags (both mainly from embryogenic cell cultures), we assembled 26670549 reads into 146786 transcripts, of which we annotated 79182 to support investigations of the molecular basis of tree aging and adaption, somatic embryogenesis and wood formation. Using these sequences we also identified many single-nucleotide polymorphisms, simple sequence repeats, and insertion and deletion markers to assist breeding and genetic diversity studies of .

关键词: Larix     transcriptome     age     wood formation     somatic embryogenesis     molecular marker    

Recent advances in understanding genetic variants associated with economically important traits in sheep (

Song-Song XU, Meng-Hua LI

《农业科学与工程前沿(英文)》 2017年 第4卷 第3期   页码 279-288 doi: 10.15302/J-FASE-2017151

摘要: Sheep are one of the most economically important domesticated animals for human society. However, genetic improvements for the key traits associated with meat, growth, milk, wool, reproduction, horns and tails progress slowly using conventional crossbreeding methods. With the development and utilization of high-throughput screening technologies over the last decade, a list of functional genes and genetic variants associated with these traits has been identified. This review covers recent genome-wide studies on sheep productive traits using high-throughput screening technologies, including those based on single-nucleotide polymorphisms and copy number variants at the whole-genome level (e.g., genome-wide association studies), transcriptome and DNA methylation sequences. Additionally, comprehensive information on functional genes and genetic variants associated with economically important traits in sheep is provided.

关键词: sheep     high-throughput screening     productive traits     genome-wide studies    

Genetic Study Identifies CBLN4 as a Novel Susceptibility Gene for Accident Proneness

Shu-lin Zhang,Hui-qing Jin,Yang Song,Wan-sheng Yu,Liang-dan Sun

《工程管理前沿(英文)》 2016年 第3卷 第1期   页码 30-38 doi: 10.15302/J-FEM-2016008

摘要: Frequent traffic accidents constitute a major danger to human beings. The accident-prone driver who has the stable physiological, psychological, and behavioral characteristics is one of the most prominent causes of traffic accidents. The internal link between the individual characteristics and the accident proneness has been a difficult point in the accident prevention research. The authors selected accident-prone drivers as cases and safe drivers as controls (case-control group) from 18,360 drivers who were enrolled from three public transportation incorporations of China using area stratified sampling method. The case-control groups were 1:1 matched. The authors performed genome-wide association study (GWAS) by 179 cases and 179 controls using the U.S. Affymetrix Genome-Wide Human Mapping SNP 6.0 Array. The authors observed that the gene frequencies of 34 single-nucleotide polymorphisms (SNPs) in three regions of cases were higher than those in the control ( <10 ). The authors then tested two independent replication sets for strong association 6 SNPs in 349 pairs of case-control drivers using the U.S. ABI 3730 sequencing method. The results indicated that SNP rs6069499 within linked CBLN4 gene are strongly associated with accident proneness ( =6.37×10 ). According to CBLN4 gene mainly involved in adrenal development and the regulation of secretion, the authors performed 12 biochemical parameters of the blood using radioimmunoassay. The levels of dopamine (DA) and adrenocorticotropic (ACTH) hormone showed significant differences between accident-prone drivers and safe drivers ( =0.03, =0.01). It is suggested that the accident-prone drivers may have the idiosyncrasy of susceptibility.

关键词: accident proneness     genome-wide association study (GWAS)     dopamine (DA)     ACTH     susceptibility gene     traffic accident epidemiology     accident prevention     traffic safety     three-dimensional model    

Development of Machine Learning Methods for Accurate Prediction of Plant Disease Resistance

Qi Liu,Shi-min Zuo,Shasha Peng,Hao Zhang,Ye Peng,Wei Li,Yehui Xiong,Runmao Lin,Zhiming Feng,Huihui Li,Jun Yang,Guo-Liang Wang,Houxiang Kang,

《工程(英文)》 doi: 10.1016/j.eng.2024.03.014

摘要: The traditional method of screening plants for disease resistance phenotype is both time-consuming and costly. Genomic selection offers a potential solution to improve efficiency, but accurately predicting plant disease resistance remains a challenge. In this study, we evaluated eight different machine learning (ML) methods, including random forest classification (RFC), support vector classifier (SVC), light gradient boosting machine (lightGBM), random forest classification plus kinship (RFC_K), support vector classification plus kinship (SVC_K), light gradient boosting machine plus kinship (lightGBM_K), deep neural network genomic prediction (DNNGP) and densely connected convolutional networks (DenseNet), for predicting plant disease resistance. Our results demonstrate that the three plus kinship (K) methods developed in this study achieved high prediction accuracy. Specifically, these methods achieved accuracies of up to 95% for rice blast (RB), 85% for rice black-streaked dwarf virus (RBSDV), and 85% for rice sheath blight (RSB) when trained and applied to the rice diversity panel I (RDPI). Furthermore, the plus K models performed well in predicting wheat blast (WB) and wheat stripe rust (WSR) diseases, with mean accuracies of up to 90% and 93%, respectively. To assess the generalizability of our models, we applied the trained plus K methods to predict RB disease resistance in an independent population, rice diversity panel II (RDPII). Concurrently, we evaluated the RB resistance of RDPII cultivars using spray inoculation. Comparing the predictions with the spray inoculation results, we found that the accuracy of the plus K methods reached 91%. These findings highlight the effectiveness of the plus K methods (random forest classification plus kinship (RFC_K), support vector classification plus kinship (SVC_K), and light gradient boosting machine plus kinship (lightGBM_K)) in accurately predicting plant disease resistance for RB, RBSDV, RSB, WB, and WSR. The methods developed in this study not only provide valuable strategies for predicting disease resistance but also pave the way for using machine learning to streamline genome-based crop breeding.

关键词: Predicting plant disease resistance (PPDR)     Genomic selection (GS)     Machine learning (ML)     Genome-wide association study (GWAS)    

Genome-wide search for candidate genes determining vertebrae number in pigs

Longchao ZHANG, Jingwei YUE, Xin LIU, Jing LIANG, Kebin ZHAO, Hua YAN, Na LI, Lei PU, Yuebo ZHANG, Huibi SHI, Ligang WANG, Lixian WANG

《农业科学与工程前沿(英文)》 2017年 第4卷 第3期   页码 327-334 doi: 10.15302/J-FASE-2017163

摘要: Longer porcine carcasses may be expected to have more vertebrae. Therefore, vertebrae number in pigs is an economically important trait. To examine the genetic basis of this trait, we genotyped 578 F Large White × Minzhu pigs using the Porcine SNP60K BeadChip. A genome-wide association study (GWAS) identified 36 significant single nucleotide polymorphisms (SNPs) on the chromosomes SSC1 (294.28–300.32 Mb) and SSC7 (102.22–109.39 Mb). A 6.04-Mb region that contained all 13 significant SNPs on SSC1 also contained the gene , previously reported to influence the number of vertebrae in pigs. However, the reported putative casual mutation of c.748C>T showed no genome-wide significant association with the trait, suggesting it was not a causal mutation in our population. The remaining 23 significant SNPs on SSC7 were concentrated in a 7.17-Mb region, which was within a quantitative trait locus interval for number of vertebrae. was the closest gene to the most significant SNP and might be a candidate. Haplotype sharing and block analysis refined the QTL to an interval of about 3 Mb containing 29 candidate genes. Of these 29 genes, the previously reported possible casual mutation of g.19034A>C was not found to be a causal mutation in our population. Exploration of these genes via additional genetic and functional studies in mammals revealed that could be a good candidate on SSC7. A mutation of c.1749G>A was detected by GWAS and could be proposed as a candidate causal mutation, or as closely linked to a causal mutation, for the number of vertebrae in pigs.

关键词: genome-wide association study     number of vertebrae     pig     SSC7     TGFβ3    

Genome-wide identification and expression analysis of the β-amylase genes strongly associated with fruit

Hongxia MIAO,Peiguang SUN,Yulu MIAO,Juhua LIU,Jianbin ZHANG,Caihong JIA,Jingyi WANG,Zhuo WANG,Zhiqiang JIN,Biyu XU

《农业科学与工程前沿(英文)》 2016年 第3卷 第4期   页码 346-356 doi: 10.15302/J-FASE-2016127

摘要: β-amylase (BAM) is an important enzyme involved in conversion of starch to maltose in multiple biological processes in plants. However, there is currently insufficient information on the BAM gene family in the important fruit crop banana. This study identified 16 genes in the banana genome. Phylogenetic analysis showed that MaBAMs were classified into four subfamilies. Most in each subfamily shared similar gene structures. Conserved motif analysis showed that all identified MaBAM proteins had the typical glyco hydro 14 domains. Comprehensive transcriptomic analysis of two banana genotypes revealed the expression patterns of in different tissues, at various stages of fruit development and ripening, and in responses to abiotic stresses. Most s showed strong transcript accumulation changes during fruit development and late-stage ripening. Some showed significant changes under cold, salt, and osmotic stresses. This finding indicated that might be involved in regulating fruit development, ripening, and responses to abiotic stress. Analysis of five hormone-related and seven stress-relevant elements in the promoters of further revealed that BAMs participated in various biological processes. This systemic analysis provides new insights into the transcriptional characteristics of the genes in banana and may serve as a basis for further functional studies of such genes.

关键词: β-amylase     banana     genome-wide identification     fruit development     abiotic stress    

U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control

null

《医学前沿(英文)》 2015年 第9卷 第4期   页码 478-486 doi: 10.1007/s11684-015-0420-0

摘要:

Telomeres play a critical role in biological ageing by maintaining chromosomal integrity and preventing chromosome ends fusion. Epidemiological studies have suggested that inter-individual differences of telomere length could affect predisposition to multiple cancers, but evidence regarding esophageal squamous cell carcinoma (ESCC) was still uncertain. Several telomere length-related single nucleotide polymorphisms (TL-SNPs) in Caucasians have been reported in genome-wide association studies. However, the effects of telomere length and TL-SNPs on ESCC development are unclear. Therefore, we conducted a case-control study (1045 ESCC cases and 1433 controls) to evaluate the associations between telomere length, TL-SNPs, and ESCC risk in Chinese population. As a result, ESCC cases showed overall shorter relative telomere length (RTL) (median: 1.34) than controls (median: 1.50, P<0.001). More interestingly, an evident nonlinear U-shaped association was observed between RTL and ESCC risk (P<0.001), with odds ratios (95% confidence interval) equal to 2.40 (1.84–3.14), 1.36 (1.03–1.79), 1.01 (0.76–1.35), and 1.37 (1.03–1.82) for individuals in the 1st (the shortest), 2nd, 3rd, and 5th (the longest) quintile, respectively, compared with those in the 4th quintile as reference group. No significant associations were observed between the eight reported TL-SNPs and ESCC susceptibility. These findings suggest that either short or extremely long telomeres may be risk factors for ESCC in the Chinese population.

关键词: esophageal squamous cell carcinoma     telomere length     genetic variants     susceptibility     genome-wide association study    

The predictive value of chromosome 8p deletion for metastasis of hepatocellular carcinoma: a summary of works in 10 years

QIN Lunxiu, TANG Zhaoyou, GUAN Xinyuan, YE Qinghai, JIA Huliang, REN Ning

《医学前沿(英文)》 2008年 第2卷 第3期   页码 211-215 doi: 10.1007/s11684-008-0041-y

摘要: Hepatocellular carcinoma (HCC) represents an extremely poor prognostic cancer, which is mainly due to the high frequency of metastasis/recurrence after surgical operation. Exploring the molecular mechanisms involved in HCC metastasis could be helpful in the prediction and early diagnosis of HCC recurrence and could also provide new therapeutic targets for HCC metastasis. In the recent decade, we analyzed the genomic aberrations of the clinical specimens, as well as the metastatic models and cell lines of human HCC to identify the genetic markers related to HCC metastasis and to verify their clinical values in the prediction and control of metastasis of HCC. Using the comparative genomic hybridization (CGH) technique, we compared the differences of chromosomal aberrations between primary HCC tumors and their matched metastatic lesions, and found that chromosome 8p deletions might contribute to HCC metastasis. This novel finding was further confirmed by comparison between nude mice models of HCC with different metastatic potentials. By the more sensitive genome-wide microsatellite analysis, 8p deletion was defined to 8p23.3 and 8p11.2, which are two likely regions harboring metastasis-related genes of HCC. Using ‘8p-specific’ microarrays, two novel metastatic suppressors ( and ) were identified, and were proven to suppress invasion and metastasis of HCC. Clinical studies indicate that 8p deletion detected in HCC or circulating plasma DNA of patients is a useful predictor for metastatic recurrence and prognosis, even for patients with early stage HCC. These novel findings are regarded as important advances in the study of the molecular mechanisms of HCC metastasis, which provide not only a holistic view on the molecular cytogenetic bases of HCC metastasis, but also candidate regions for further study to identify metastatic suppressor genes.

关键词: sensitive genome-wide     prediction     genome-wide microsatellite     frequency     Hepatocellular carcinoma    

标题 作者 时间 类型 操作

Genome-wide association studies: inherent limitations and future challenges

null

期刊论文

Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies

null

期刊论文

A genome-wide association study of five meat quality traits in Yorkshire pigs

Qian DONG,Huiying LIU,Xinyun LI,Wei WEI,Shuhong ZHAO,Jianhua CAO

期刊论文

Genome-wide association study of the backfat thickness trait in two pig populations

Dandan ZHU,Xiaolei LIU,Rothschild MAX,Zhiwu ZHANG,Shuhong ZHAO,Bin FAN

期刊论文

Genome-wide association analysis reveals genetic loci and candidate genes associated with intramuscular

Xingwang WANG, Rongrong DING, Jianping QUAN, Linxue YANG, Ming YANG, Enqin ZHENG, Dewu LIU, Gengyuan CAI, Zhenfang WU, Jie YANG

期刊论文

近十二年人类蛋白质N-糖基化的全基因组关联研究综述

Anna Timoshchuk, Sodbo Sharapov, Yurii S. Aulchenko

期刊论文

Systems understanding of plant–pathogen interactions through genome-wide protein–protein interaction

Hong LI,Ziding ZHANG

期刊论文

Transcriptome resources and genome-wide marker development for Japanese larch (

Wanfeng LI,Suying HAN,Liwang QI,Shougong ZHANG

期刊论文

Recent advances in understanding genetic variants associated with economically important traits in sheep (

Song-Song XU, Meng-Hua LI

期刊论文

Genetic Study Identifies CBLN4 as a Novel Susceptibility Gene for Accident Proneness

Shu-lin Zhang,Hui-qing Jin,Yang Song,Wan-sheng Yu,Liang-dan Sun

期刊论文

Development of Machine Learning Methods for Accurate Prediction of Plant Disease Resistance

Qi Liu,Shi-min Zuo,Shasha Peng,Hao Zhang,Ye Peng,Wei Li,Yehui Xiong,Runmao Lin,Zhiming Feng,Huihui Li,Jun Yang,Guo-Liang Wang,Houxiang Kang,

期刊论文

Genome-wide search for candidate genes determining vertebrae number in pigs

Longchao ZHANG, Jingwei YUE, Xin LIU, Jing LIANG, Kebin ZHAO, Hua YAN, Na LI, Lei PU, Yuebo ZHANG, Huibi SHI, Ligang WANG, Lixian WANG

期刊论文

Genome-wide identification and expression analysis of the β-amylase genes strongly associated with fruit

Hongxia MIAO,Peiguang SUN,Yulu MIAO,Juhua LIU,Jianbin ZHANG,Caihong JIA,Jingyi WANG,Zhuo WANG,Zhiqiang JIN,Biyu XU

期刊论文

U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control

null

期刊论文

The predictive value of chromosome 8p deletion for metastasis of hepatocellular carcinoma: a summary of works in 10 years

QIN Lunxiu, TANG Zhaoyou, GUAN Xinyuan, YE Qinghai, JIA Huliang, REN Ning

期刊论文