基于TCGA数据库免疫基因表达谱构建253例宫颈鳞状细胞癌免疫亚组

目的 采用美国肿瘤基因组图谱(TCGA)数据库免疫基因表达谱构建宫颈鳞状细胞癌免疫亚型,并分析各免疫亚组特征,为宫颈鳞状细胞癌预后分析及治疗提供新指标.方法 TCGA数据库共下载253例宫颈鳞状细胞癌及3例癌旁正常组织的mRNA表达谱及临床数据.根据单样本基因集富集分析(ssGSEA)得分情况,将宫颈鳞状细胞癌分为高免...     

Amplification Artifact in SARS-CoV-2 Omicron Sequences Carrying P681R Mutation,New York,USA

Of 379 severe acute respiratory syndrome coronavirus 2 samples collected in New York, USA, we detected 86 Omicron variant sequences containing Delta variant mutation P681R. Probable explanations were co-infection with 2 viruses or contamination/amplification artifact. Repeated library preparation with fewer cycles showed the P681R calls were artifactual. Unusual mutations should be interpreted with caution.     

Automation and developmental validation of the ForenSeq™ DNA Signature Preparation kit for high-throughput analysis in forensic laboratories

Massively parallel sequencing (MPS) applications in forensic science highlight the advantages of this technique compared to capillary electrophoresis (CE). The multiplexing of a wide range of genetic markers and access to the full amplicon sequence, allowing the detection of isoalleles, make it a very promising tool which could be applied to the most challenging casework DNA samples. However, the complexity of the manual library preparation protocol, potential DNA contamination and sample tracking issues are the main reasons why forensic scientists still hesitate to implement MPS analytical workflows in their laboratory. Here, we present the automation of all library preparation steps for up to 96 samples using the Verogen’s ForenSeq^™ DNA Signature Preparation kit. This automated protocol, developed on a Hamilton ID STARlet robotic platform, is designed to allow the combined sequencing of rich and poor DNA samples thanks to a final step which adjusts normalized library pooling volume to guarantee a uniform depth of coverage across all samples. Our study includes tests of concordance, repeatability, reproducibility and sensitivity (1000 pg, 700 pg, 500 pg, 250 pg, 100 pg and 50 pg). Sequencing results obtained with the automated protocol were found to be concordant with previous validation studies using the manual protocol in terms of depth of coverage and allele coverage ratio. The results of this study will assist forensic laboratories seeking to acquire a plug and play solution to optimize the processing and analysis of casework samples with MPS.     

Pathophysiology of asthma: lessons from genetic research with particular focus on severe asthma

There is good evidence that both inherited and environmental factors influence the risk of developing asthma. Only recently, large well-designed studies have been undertaken with the power to identify the genetic causes for asthma, and methods developed in parallel with the Human Genome Project, such as gene expression and epigenetic studies, have made large-scale analyses of functional genetics possible. In this review, we discuss the recent findings from genetic and genomic research studies of asthma, particularly severe asthma, and highlight specific genes for which there are multiple lines of evidence for involvement in asthma pathogenesis. Bio-ontologic enrichment analyses of the most recently identified asthma-related genes point to attributes such as 'molecular and signal transducer activity' and 'immune system processes', which indicates the importance of immunoregulation and inflammatory response in the pathogenesis of asthma. Finally, we discuss how genetic and environmental factors jointly influence asthma susceptibility and summarize how the results may increase understanding of the pathophysiology of asthma-related diseases.     

Complete genome sequence of Vibrio fischeri: a symbiotic bacterium with pathogenic congeners

Vibrio fischeri belongs to the Vibrionaceae, a large family of marine gamma-proteobacteria that includes several dozen species known to engage in a diversity of beneficial or pathogenic interactions with animal tissue. Among the small number of pathogenic Vibrio species that cause human diseases are Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus, the only members of the Vibrionaceae that have had their genome sequences reported. Nonpathogenic members of the genus Vibrio, including a number of beneficial symbionts, make up the majority of the Vibrionaceae, but none of these species has been similarly examined. Here we report the genome sequence of V. fischeri ES114, which enters into a mutualistic symbiosis in the light organ of the bobtail squid, Euprymna scolopes. Analysis of this sequence has revealed surprising parallels with V. cholerae and other pathogens.     

Comparative sequencing provides insights about the structure and conservation of marsupial and monotreme genomes

Sequencing and comparative analyses of genomes from multiple vertebrates are providing insights about the genetic basis for biological diversity. To date, these efforts largely have focused on eutherian mammals, chicken, and fish. In this article, we describe the generation and study of genomic sequences from noneutherian mammals, a group of species occupying unusual phylogenetic positions. A large sequence data set (totaling >5 Mb) was generated for the same orthologous region in three marsupial (North American opossum, South American opossum, and Australian tammar wallaby) and one monotreme (platypus) genomes. These ancient mammalian genomes are characterized by unusual architectural features with respect to G + C and repeat content, as well as compression relative to human. Approximately 14% and 34% of the human sequence forms alignments with the orthologous sequence from platypus and the marsupials, respectively; these numbers are distinctly lower than that observed with nonprimate eutherian mammals (45-70%). The alignable sequences between human and each marsupial species are not completely overlapping (only 80% common to all three species) nor are the platypus-alignable sequences completely contained within the marsupial-alignable sequences. Phylogenetic analysis of synonymous coding positions reveals that platypus has a notably long branch length, with the human-platypus substitution rate being on average 55% greater than that seen with human-marsupial pairs. Finally, analyses of the major mammalian lineages reveal distinct patterns with respect to the common presence of evolutionarily conserved vertebrate sequences. Our results confirm that genomic sequence from noneutherian mammals can contribute uniquely to unraveling the functional and evolutionary histories of the mammalian genome.