刺果甘草全基因组Survey及叶绿体基因组特征分析＊

目的 基于基因组Survey分析对刺果甘草Glycyrrhiza pallidiflora Maxim.基因组大小和杂合率进行估计，并通过叶绿体基因组序列特征对其在甘草属Glycyrrhiza L.中的系统发育位置进行研究。方法 使用二代测序技术对刺果甘草进行测序，采用K-mer方法对测序reads进行分析，估算刺果甘草基因组大小和杂合率，使用生物信息学方法进行叶绿体基因组组装、注释和系统发育分析。结果 Survey分析结果显示其基因组大小约为577.82 Mb，杂合度约为0.31%，重复序列比例约为53.72%。叶绿体基因组长度为127，267 bp，不具有典型的四分体结构，总GC含量为34.32%，包含110个基因，其中76个蛋白质编码基因，30个tRNA基因和4个rRNA基因。系统发育分析表明，刺果甘草与圆果甘草G. squamulosa Franch.亲缘较接近。结论 刺果甘草存在低杂合和重复序列较多的特点，为了更好地对全基因组进行序列拼接和组装，可尝试采用三代测序结合二代测序的分析策略进行基因组组装；刺果甘草叶绿体全基因组比对和系统发育分析，为后续开展甘草属遗传多样性研究和分子鉴定标记筛选提供了重要依据。     

Effect of Race and Ethnicity on Risk of Radiotherapy Toxicity and Implications for Radiogenomics

AimsPatient factors affect the risk of radiotherapy toxicity, but many are poorly defined. Studies have shown that race affects cancer incidence, survival, drug response, molecular pathways and epigenetics. Effects on radiosensitivity and radiotherapy toxicity are not well studied. The aim of the present study was to identify the effects of race and ethnicity on the risk of radiotherapy toxicity.Materials and methodsA systematic review was carried out of PubMed, Ovid Medline and Ovid Embase with no year limit. PRISMA 2020 guidelines were followed. Two independent assessors reviewed papers.ResultsOf 607 papers screened, 46 fulfilled the inclusion criteria. Papers were published between 1996 and 2021 and involved 30–28,354 individuals (median 433). Most involved patients with prostate (33%), breast (26%) and lung (9%) cancer. Both early and late toxicities were studied. Some studies reported a higher risk of toxicity in White men with prostate cancer compared with other races and ethnicities. For breast cancer patients, some reported an increased risk of toxicity in White women compared with other race and ethnic groups. In general, it was difficult to draw conclusions due to insufficient reporting and analysis of race and ethnicity in published literature.ConclusionsReporting of race and ethnicity in radiotherapy studies must be harmonised and improved and frameworks are needed to improve the quality of reporting. Further research is needed to understand how ancestral heritage might affect radiosensitivity and risk of radiotherapy toxicity.     

Association of expression quantitative trait loci for long noncoding RNAs with lung cancer risk in Asians

Identification of long noncoding RNA (lncRNA) expression quantitative trait loci (lncR‐eQTL) that associated with lung cancer can provide insights into regulatory mechanisms of lncRNA, and help reveal the role of lncRNA in lung cancer. A two‐stage case‐control design was implemented in this study. We first selected the lncRNAs that differently expressed based on the Cancer Genome Atlas (TCGA) project (75 normal and 708 tumor tissues) and identified eQTLs for selected lncRNAs based on data of 278 normal lung tissues from the the genotype‐tissue expression database. Then we selected lncR‐eQTLs that associated with lung cancer based on two lung cancer GWAS datasets (7127 cases and 6818 controls). Promising lncR‐eQTLs were further replicated in an additional population (1056 cases and 1053 controls). Functional annotations of the identified lncR‐eQTLs and related lncRNAs were finally performed by using multiple public databases. Our eQTL analysis finally detected three lncRNA‐eQTLs, rs793544 in 3q13.12 (odds ratio [OR] = 1.15; confidence interval [CI]:1.09‐1.22; P = 2.30 × 10^?6), rs7234707 in 18p11.31 (OR = 1.1; CI:1.05‐1.15; P = 9.01 × 10^?5) and rs1600249 in 8p23.1 (OR = 1.1; CI:1.05‐1.16; P = 1.27 × 10^?4), that were consistently associated with the risk of lung cancer. These findings indicate that lncR‐eQTLs may serve as novel susceptibility markers for lung cancer.     

Reconceptualizing anorexia nervosa

Anorexia nervosa (AN) has one of the highest mortality rates of any psychiatric disorder. Treatments are often ineffective and relapse is common. Most research attempting to understand the underlying causes and maintenance factors of AN has focused on environmental contributions, yet there is much to be explored in terms of biological risk and maintenance factors. In this paper, we focus primarily on AN research related to genetics and the complex microbial community in the gut (intestinal microbiota), and how these impact our conceptualization of this disorder. Emerging research identifying significant negative genetic correlations between AN and obesity suggests that the conditions may represent ‘metabolic bookends’. The identification of underlying biological mechanisms may provide both insight into extreme weight dysregulation on both ends of the spectrum and new possible points of entry for AN treatment. Additionally, the reported microbial imbalance (dysbiosis) in the gut microbiota in AN patients, potentially due to a nutrient‐ and energy‐deprived gut environment, implies alterations in functional and metabolic capacity of the gut microbiome. The extent to which AN and obesity can also be considered to be ‘microbiome bookends’ requires further investigation. Finally, we discuss ongoing and future AN projects exploring the interplay between host genomics, the environment, and cumulative microbial genomes (microbiome) as well as interventions at the microbial and gut level.     

Japanese version of The Cancer Genome Atlas,JCGA, established using fresh frozen tumors obtained from 5143 cancer patients

This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single‐center study called “High‐tech Omics‐based Patient Evaluation” or “Project HOPE” conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole‐exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed “Shizuoka Multi‐omics Analysis Protocol” developed in‐house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non–cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients.     

冠状病毒复制分子生物学与防控措施研发进展

目的以新冠肺炎致病菌2019-nCoV,中东呼吸综合征相关冠状病毒MERS-CoV和严重急性呼吸综合征相关冠状病毒SARS-CoV为代表的冠状病毒成为最近重大公共卫生关注焦点。研发更好的防控措施需要更好地认识冠状病毒,尤其是其基因组和复制分子生物学。方法文献综述和基因组序列分析。结果全球14673篇相关文章,美国NCBI有40个冠状病毒全基因组序列,GEO(Gene expression omnibus)有33个冠状病毒相关转录组数据。结论冠状病毒基因组具有独特的性质,复制特点,不少病毒蛋白具有多功能,包括与宿主相互作用,影响宿主蛋白质翻译后修饰如泛素化和去泛素化,调控宿主免疫病理。这些为疫苗、诊断和药物等新防控措施研发提供了基础。     

肺腺癌竞争内源性RNA网络的综合分析:基于肿瘤基因组图谱数据库

目的:基于肿瘤基因组图谱数据库（TCGA）架构肺腺癌（LUAD）竞争内源性RNA（ceRNA）网络，鉴定潜在的生存关联性生物标志物，并确定特异性治疗的小分子药物。方法:依据纳入研究标准，利用Edger软件筛选LUAD组织与正常组织(mRNA、lncRNA和miRNA)差异表达的基因。通过miRcode、miRDB、TargetScan和miRanda数据库对差异表达的RNA之间的关系进行分析，构建ceRNA网络。采用Kaplan-Meier方法分析ceRNA网络中的RNA表达量与生存预后的关系，通过富集分析对网络中的mRNA基因功能和调控通路进行分析。通过Cmap数据库筛选治疗LUAD的特异性小分子药物。利用D-lnc软件确定与关键的lncRNA相关的特异性小分子药物。结果:mRNAs(ELAVL2和PBK)、miRNAs(miR-13和miR-210)和lncRNAs(AP002478.1、DSCAM-AS1、LINC00269、LINC00470和LINC00483)与总生存期(OS)关系密切。喜树碱和甲萘醌有可能逆转LUAD的状态。卡铂、多西紫杉醇、帕比司他被确定为与关键lncRNA密切相关的药物。结论:ceRNA网络在LUAD中发挥重要作用，多种差异表达RNA与LUAD预后相关，可能成为潜在的肿瘤诊断标志物和治疗靶点。     

Molecular pathogenesis of spontaneous abortions – Whole genome copy number analysis and expression of angiogenic factors

ObjectiveTo study two major molecular alterations in spontaneous abortions (SA) with unexplained etiology – fetal genomic anomalies and the endometrial expression of main angiogenic factors VEGFA/VEGFR2 and chemokines SDF-1/CXCR4.Materials and methodsWhole genome copy number analysis by arrayCGH or Next Generation Sequencing (NGS) was applied for detection of fetal genomic imbalances. The abortive decidua of SA without fetal aneuploidies was further investigated for expression levels of the abovementioned factors using real time PCR analysis. A total of 30 abortive materials were collected from spontaneous abortions after exclusion of known predisposing factors.ResultsIn 21 of 30 spontaneous abortions (70%), genomic anomalies were discovered by whole genome copy number analysis. Numerical anomalies were detected in 90% of aberrant cases, and in 10% - structural aberrations were revealed. An increased expression for essential factors of angiogenesis was identified in spontaneous abortions’ tissues - 3.44 times for VEGFA and 10.29 times for VEGFR2. We found an average of 14 times increase in the expression levels of SDF-1 and 3.21 times for its receptor CXCR4.ConclusionWe could suggest the occurrence of increased angiogenesis in SA without fetal aneuploidies, compared to the control tissues, which could lead to increased oxidative stress and fetal loss.     

Impermanence of bacterial clones

Bacteria reproduce asexually and pass on a single genome copied from the parent, a reproductive mode that assures the clonal descent of progeny; however, a truly clonal bacterial species is extremely rare. The signal of clonality can be interrupted by gene uptake and exchange, initiating homologous recombination that results in the unique sequence of one clone being incorporated into another. Because recombination occurs sporadically and on local scales, these events are often difficult to recognize, even when considering large samples of completely sequenced genomes. Moreover, several processes can produce the appearance of clonality in populations that undergo frequent recombination. The rates and consequences of recombination have been studied in Escherichia coli for over 40 y, and, during this time, there have been several shifting views of its clonal status, population structure, and rates of gene exchange. We reexamine the studies and retrace the evolution of the methods that have assessed the extent of DNA flux, largely focusing on its impact on the E. coli genome.