基于多组学数据的早期宫颈鳞状细胞癌分类

从分子层面对泛癌进行研究已经得到了很大的进展,但是对宫颈鳞状细胞癌的分子分类研究仍然需要更多的探索.为了找到宫颈鳞状细胞癌潜在的子类,本文提出了一个基于多维组学数据的癌症亚型分类分析流程.通过统计学方法对癌症基因组图谱(The Cancer Genome Atlas,TCGA)宫颈鳞状细胞癌的mRNA表达数据、小分子核糖核酸(microRNA,miRNA)表达数据、DNA甲基化数据以及拷贝数变异数据4个维度包含的分子进行筛选,然后对筛选后的分类特征进行整合聚类,进一步筛选能够区分不同子类的关键分类特征,并使用这些关键分类特征建立宫颈鳞状细胞癌分类模型.本研究为宫颈鳞状细胞癌分子层面子类的识别提供了分析流程,得到了两个临床生存水平具有显著性差异的宫颈鳞状细胞癌子类,并确定了8个宫颈鳞状细胞癌的关键分类特征.本研究中识别的宫颈鳞状细胞癌子类和关键分类特征为宫颈鳞状细胞癌早期分类及分类标志物的鉴定提供了重要参考.

Multi-Omics and Its Clinical Application in Hepatocellular Carcinoma:Current Progress and Future Opportunities

Hepatocellular carcinoma(HCC)is the sixth most common malignancy and the fourth leading cause of cancer related death worldwide.China covers over half of cases,leading HCC to be a vital threaten to public health.Despite advances in diagnosis and treatments,high recurrence rate remains a major obstacle in HCC management.Multi-omics currently facilitates surveillance,precise diagnosis,and personalized treatment decision making in clinical setting.Non-invasive radiomics utilizes preoperative radiological imaging to reflect subtle pixel-level pattern changes that correlate to specific clinical outcomes.Radiomics has been widely used in histopathological diagnosis prediction,treatment response evaluation,and prognosis prediction.High-throughput sequencing and gene expression profiling enabled genomics and proteomics to identify distinct transcriptomic subclasses and recurrent genetic alterations in HCC,which would reveal the complex multistep process of the pathophysiology.The accumulation of big medical data and the development of artificial intelligence techniques are providing new insights for our better understanding of the mechanism of HCC via multi-omics,and show potential to convert surgical/intervention treatment into an antitumorigenic one,which would greatly advance precision medicine in HCC management.

Functional genomic approach to the study of biodiversitywithin Trichoderma

Trichoderma is a fungal genus of great and demonstrable biotechnological value, but its genome is poorly surveyed compared with other model microorganisms. Due to their ubiquity and rapid substrate colonization, Trichoderma species have been widely used as biocontrol organisms for agriculture, and their enzyme systems are widely used in industry. Therefore, there is a clear interest to explore beyond the phenotype to exploit the underlying genetic systems using functional genomics tools. The great diversity of species within the Trichoderma genus, the absence of optimized systems for its exploration, and the great variety of genes expressed under a wide range of ambient conditions are the main challenges to consider when starting a comprehensive functional genomics study. An initial project started by three Spanish groups has been extended into the project TRICHOEST, funded by the EU (FP5, QLRT-2001-02032) to target the transcriptome analysis of selected Trichoderma strains with biocontrol potential, in conditions related to antagonism, nutrient stress and plant interactions. Once specific conditions were defined, cDNA libraries were produced and used for EST sequencing. Nine strains from seven Trichoderma species have been considered in this study and an important amount of gene sequence data has been generated, analyzed and used to compare the gene expression in different strains. In parallel to sequencing, genomic expression studies were carried out by means of macro-arrays to identify genes expressed in specific conditions. In silico analysis of DNA sequencing data together with macro-array expression results have lead to a selection based on the potential use of the gene sequences. The selected clone sequences were completed and cloned in appropriate vectors to initiate functional analysis by means of expression studies in homologous and heterologous systems.

Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significanly correlated with cytochrome P450 suppression

AIM： To investigate the hepatoprotective activity of tea polyphenols （TP） and its relation with cytochrome P450 （CYP450） expression in mice. METHODS： Hepatic CYP450 and CYPbs levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP （25, 50 and 100 mg/kg per day）. Then the mice were intragastricly pre-treated with TP （100, 200 and 400 mg/kg per day） for six days before paracetamol （1000 mg/kg） was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP （100, 200, and 400 mg/kg per day） for five days before paracetamol （500 mg/kg） was given. Hepatic CYP2E1 and CYPIA2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction. RESULTS： The hepatic CYP450 and CYPb5 levels in mice of TP-treated groups （100, 200 and 400 mg/kg per day） were decreased in a dose-dependent manner compared with those in the negative control mice.TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYPIA2 expression at both protein and mRNA levels in a dose-dependent manner. CONCLUSION： TP possess potential hepatoprotective properties and can suppress CYP450 expression.

Genomic insights into the ESBL and MCR-l-producing ST648 Escherichia coli with multi-drug resistance

Polymyxin acts as an ultimate line of refuge against the severe infections by multidrug-resistant Gram- negative pathogens. This conventional idea is challenged dramatically by the recent discovery of mobile colistin resistance gene （mcr-1） is prevalent in food animals and human beings worldwide. More importantly, the mcr-1 gene was found to be co-localized with other antibiotic resistance genes, raising the possibility that super-bugs with pan-drug resistance are emerging. However, little is reported on the genomes of the mcr-l-positive bacterial host reservoirs. Here we report genome sequencing of three human isolates of the mcr-l-positive Escherichia coli （E15004, E15015 and E15017） and define general features through analyses of bacterial comparative genomics. Fur- ther genomic mining together with sequence typing allowed us to elucidate that the MCR-l-carrying E. coli E15017 belongs to the sequence type ST648 and copro- duces extended-spectrum β-1actamase （ESBL）. Given the fact that ST648 has been known to associate New Delhi metallo-β-1actamase 1 or ESBL, with either our results highlighted the possibility of ST648 as an epidemic clone with multidrug resistances.

Genomics and introgression： Discovery and mapping of thousands of species-diagnostic SNPs using RAD sequencing

Invasive hybridization and introgression pose a serious threat to the persistence of many native species. Understand- ing the effects of hybridization on native populations （e.g., fitness consequences） requires numerous species-diagnostic loci dis- tributed genome-wide. Here we used RAD sequencing to discover thousands of single-nucleotide polymorphisms （SNPs） that are diagnostic between rainbow trout （RBT, Oncorhynchus mykiss）, the world＇s most widely introduced fish, and native westslope cutthroat trout （WCT, （9. clarkii lewisi） in the northern Rocky Mountains, USA. We advanced previous work that identified 4,914 species-diagnostic loci by using longer sequence reads （100 bp vs. 60 bp） and a larger set of individuals （n = 84）. We sequenced RAD libraries for individuals from diverse sampling sources, including native populations of WCT and hatchery broodstocks of WCT and RBT. We also took advantage of a newly released reference genome assembly for RBT to align our RAD loci. In total, we discovered 16,788 putatively diagnostic SNPs, 10,267 of which we mapped to anchored chromosome locations on the RBT genome. A small portion of previously discovered putative diagnostic loci （325 of 4,914） were no longer diagnostic （i.e., fixed between species） based on our wider survey of non-hybridized RBT and WCT individuals. Our study suggests that RAD loci mapped to a draft genome assembly could provide the marker density required to identify genes and chromosomal regions in- fluencing selection in admixed populations of conservation concern and evolutionary interest [Current Zoology 61 （1）： 146-154, 2015].

Psychrotolerant methanogenic archaea:Diversity and cold adaptation mechanisms

Because of their diversity and abundance in a wide range of environments, particularly in cold regions, cold-adaptive archaea are expected to play a pivotal role in material recycling in cold environments. Methanogenic archaea are ubiquitous on earth and produce a large amount of methane （CH4） as their main carbon metabolite. Methanogens are the most laboratory amenda- ble archaea. The few psychrophilic archaea that have been cultured to date are mainly affiliated with methanogens, thus make them a good model for investigating mechanisms of archaeal cold adaptation. Studies of psychrotolerant methanogens have been ongoing since the 1990s. Using Methanocoecoides burtonii, a methanogen isolated from Ace Lake in Antarctica, exten- sive studies on the genomic characteristics associated with cold adaptation have been carried out by the Cavicchioli laboratory. We recently analyzed the genome of another psychrophilic methanogen and identified the gene repertoire associated with cold adaptation. This review summarizes recent studies of psychroactive methanogens, particularly their diversity, the genomics and proteomics associated with their cold adaptation, and the cellular components and proteins likely involved in their cold protec- tion.

Correlation analysis of gene polymorphisms and β-lactam allergy

A total of 64 patients with β-lactam allergy and 30 control subjects were enrolled in a case-control study. This study is aimed to analyze the relationship between β-lactam allergy and 10 single nucleotide polymorphisms（SNPs） in interleukin-10（IL-10）, IL-13, IL-4Rα, high-affinity immunoglobulin E-receptor β chain（FcεRIβ）, interferon γ receptor 2（IFNGR2）, and CYP3A4, and within the Han Chinese population of Northwest China. Genotyping for the SNPs was conducted using the Sequenom Mass ARRAY platform. SPSS 17.0 was employed to analyze the statistical data and SHEsis was used to perform the haplotype reconstruction and analyze linkage disequilibrium of SNPs of IL-10 and IL-13. The results showed that the genotype distribution of CYP3A4 rs2242480/CT differed significantly between case and control groups of males（P=0.022; odds ratio（OR）=0.167, 95% confidence interval（CI）： 0.032–0.867）. Further analysis showed that CCA, CCG, and TAA haplotypes of IL-10 had no significant correlation in patients with β-lactam allergy. The correlation between CCT and CAC haplotypes of IL-13 and β-lactam allergy needs to be further studied. The analysis did not reveal any differences in the distribution of others gene polymorphisms between cases and controls.