生物信息学技术在生殖领域中的研究进展

生物信息学（bioinformatics）在生殖系统的研究中被广泛应用于各个技术层面,包括基因组、转录组、蛋白组和代谢组。通过数据的系统化采集和可视化处理,生殖过程中各种关键分子的作用机制正逐步被发现并阐明。生物信息学技术在生殖系统研究中的应用,既在保障严谨性和科学性的基础上有效地推动了生殖系统研究的发展与创新,如从基因组、转录组、蛋白组和代谢组等不同层次水平上分析生殖系统中不同器官的正常功能或其异常病理现象;同时也促进了生殖系统相关疾病临床诊断和治疗的进展,如在对疾病诊治中,新的临床疾病标志物及药物靶点的发现等。综述近年生殖医学前沿研究的最新生物信息学技术并总结现有生殖医学相关生物信息学研究的主要进展,这也为后续的各类研究提供了重要的方向和思路。     

The complete sequence of the Adoxophyes orana granulovirus genome

The nucleotide sequence of the Adoxophyes orana granulovirus (AdorGV) DNA genome was determined and analysed. The genome contains 99,657 bp and has an A + T content of 65.5%. The analysis predicted 119 ORFs of 150 nucleotides or larger that showed minimal overlap. Of these putative genes, 104 (87%) were homologous to genes identified previously in other baculoviruses. The mean overall amino acid identity of AdorGV ORFs was highest with CpGV ORFs at 48%. Sixty-three ORFs were conserved among all lepidopteran baculoviruses and are considered to be common baculoviral genes. Several genes reported to have major roles in baculovirus biology were not found in the AdorGV genome. These included chitinase and cathepsin, which are involved in the liquefaction of the host, which explains why AdorGV-infected insects do not degrade in a typical manner. The AdorGV genome encoded two inhibitor of apoptosis (iap) genes iap-3 and iap-5. Among all of the granuloviruses genomes there was a very high level of gene collinearity. The genes shared by AdorGV and CpGV had exactly the same order along the genome with the exception of one gene, iap-3. The AdorGV genome did not contain typical homologous region (hr) sequences. However, it contained nine repetitive regions in the genome.     

CDCA8对肝细胞癌患者预后的影响

目的：肝细胞癌预后相关的分子标志物对提高患者生存质量和改善疗效至关重要,本研究旨在探究细胞分裂周期相关基因8(cell division cycle associated 8,CDCA8)对肝细胞癌预后的影响及潜在分子机制。方法：432例肝细胞癌样本的转录组数据及对应患者的临床信息下载自肿瘤基因表达图谱（The Cancer Genome Atlas,TCGA）数据库。分析肿瘤组织和正常组织中CDCA8 mRNA差异;根据CDCA8 mRNA中位数将肝细胞癌患者分为高表达组和低表达组,绘制生存曲线。采用Kruskal检验分析CDCA8与肿瘤分期、分级和T分期的相关性。采用单因素和多因素Cox回归分析探究CDCA8能否作为肝细胞癌患者的独立预后因子。采用基因集富集分析（gene set enrichment analysis,GSEA）探究CDCA8在肝细胞癌中的潜在作用机制。结果：CDCA8在肿瘤组织中的mRNA水平明显高于正常对照组织（P<0.001）,CDCA8高表达患者的生存率明显低于低表达组（P<0.001）。随着肿瘤分期（P<0.001）、分级（P<0...     

生物钟相关基因在原发性肝细胞癌中的表达及临床意义——基于TCGA数据集分析

目的：探究生物钟相关基因在原发性肝细胞癌（简称肝癌）中的表达及意义。方法：从美国癌症和肿瘤基因图谱数据库（The Cancer Genome Atlas,TCGA）中下载肝癌数据424例,包括374例肝癌患者样本及50例正常对照样本。运用DECenter软件对51个生物钟相关基因进行差异表达分析,比较生物钟基因在肝癌患者及正常样本之间的表达情况。运用DAVID在线工具分析差异基因的GO及KEGG功能富集通路,并通过STRING数据库构建差异基因之间蛋白质相互作用网络。了解生物钟基因肝癌发生发展过程中的主要作用。结果：在374例肝癌患者样本的51个生物钟相关基因中,有21个基因在肝癌样本中表达上调（P<0.05）,3个基因表达下调（P<0.05）。生物钟基因高表达样本主要富集于Wnt信号通路、Hedgehog信号通路及Hippo信号通路（P<0.001）。参与调节昼夜节律和细胞代谢的10个生物钟基因在蛋白质相互作用网络中相关性最为紧密（P<0.001）。GO分析差异基因集中作用于调节昼夜节律、细胞代谢过程、基因表达等通路（P<0.001）。结论：生物钟相关基...     

Diagnosing,discarding, or de-VUSsing: A practical guide to (un)targeted metabolomics as variant-transcending functional tests

PurposeFor patients with inherited metabolic disorders (IMDs), any diagnostic delay should be avoided because early initiation of personalized treatment could prevent irreversible health damage. To improve diagnostic interpretation of genetic data, gene function tests can be valuable assets. For IMDs, variant-transcending functional tests are readily available through (un)targeted metabolomics assays. To support the application of metabolomics for this purpose, we developed a gene-based guide to select functional tests to either confirm or exclude an IMD diagnosis.MethodsUsing information from a diagnostic IMD exome panel, Kyoto Encyclopedia of Genes and Genomes, and Inborn Errors of Metabolism Knowledgebase, we compiled a guide for metabolomics-based gene function tests. From our practical experience with this guide, we retrospectively selected illustrative cases for whom combined metabolomic/genomic testing improved diagnostic success and evaluated the effect hereof on clinical management.ResultsThe guide contains 2047 metabolism-associated genes for which a validated or putative variant-transcending gene function test is available. We present 16 patients for whom metabolomic testing either confirmed or ruled out the presence of a second pathogenic variant, validated or ruled out pathogenicity of variants of uncertain significance, or identified a diagnosis initially missed by genetic analysis.ConclusionMetabolomics-based gene function tests provide additional value in the diagnostic trajectory of patients with suspected IMD by enhancing and accelerating diagnostic success.     

Emerging technologies from the Human Genome Project for understanding susceptibility and risk

The new technologies from the Human Genome Program provide exceptional opportunities for surveying and measuring human exposure, as well as determining susceptibility on an individual-by-individual basis. These new technologies will soon enable rapid screening of populations at risk, as well as the broader public, for a variety of genes known to be associated with increased risk. These include specific oncogenes, tumor suppressor genes and DNA repair enzymes. Use of these technologies also presents a number of ethical issues, both in screening and in use of the information about individuals. Overall, the use of rapid genotyping technologies will introduce a specificity and possible group identifiers that will present new challenges to the determination of risk within the EPA mandate.     

SARS冠状病毒基因组序列分析与抗SARS药物设计

SARS冠状病毒是诱发SARS的主要病原体，文章综述了SARS冠状病毒基因组序列分析的最新进展，SARS冠状病毒编码的蛋白酶在病毒繁殖过程中具有重要功能，可以其作为靶点进行抗SARS冠状病毒药物的筛选。     

宫颈癌患者基因组遗传不稳定性分析

目的 研究中国宫颈癌高发区宫颈癌患者基因组遗传不稳定性改变，为寻找宫颈癌相关内源因子提供依据。方法 从GenBank中选取8对微卫星DNA引物，采用PCR-变性PAGE-银染方法检测50例宫颈癌(来自高发区)活检组织及其对照(同病例血液)样品的杂合性丢失(LOH)和微卫星不稳定(MI)。结果 LOH总检出率为66％(33／50)，其中，D18S474(染色体18q21)LOH达40．5％；染色体3p21．2—3p21．3中微卫星位点D3S1478，LOH达31．7％；并且在原位癌与浸润癌中，LOH分布也有一定差异。MI在宫颈癌患者基因组中仅存在少数微卫星位点，总的发生率较低，为8％(4／50)。结论 除高危型人乳头瘤病毒(HPVhr)感染外，细胞内源基因的改变在宫颈癌发生发展过程中也起着重要作用。高频LOH位点18q21 D18S474、3p21．2-3p21．3 D3S1478可能存在潜在的宫颈癌抑癌基因。     

人类博卡病毒基因组序列与进化分析

目的 对人类博卡病毒的基因组结构、系统进化以及突变规律进行分析.方法 利用生物信息学方法如BLAST、CLUSTALW等程序对已经提交到GenBank数据库中的人类博卡病毒全基因组序列进行比对分析和系统进化分析.结果 人类博卡病毒基因组短小、结构简单;与其它博卡病毒基因组同源性高,尤其是犬细小病毒;目前GenBank中的5株人类博卡病毒根据进化关系分析可分为两群(CRD2、st2、CZ643和st1组成一群,WLL-1单独成群);统计突变发现人类博卡病毒NS1基因突变频率最小,VP1/2基因突变频率高.结论 人类博卡病毒很可能是动物博卡病毒传染给人后的变种;稳定的NS1基因很可能成为开发疫苗和防治药物的重要靶点.