Screening Linear and Circular RNA Transcripts from Stress Granules

Stress granules(SGs)are cytoplasmic ribonucleoprotein assemblies formed under stress conditions and are related to various biological processes and human diseases.Previous studies have reported the regulatory role of some proteins and linear RNAs in SG assembly.However,the relationship between circular RNAs(circRNAs)and SGs has not been discovered.Here,we screened both linear RNAs and circRNAs in SGs using improved total RNA sequencing of purified SG cores in mammalian cells and identified circular transcripts specifically localized in SGs.circRNAs with higher SG-related RNA-binding protein(RBP)binding abilities are more likely to be enriched in SGs.Furthermore,some SG-enriched circRNAs are differentially expressed in hepatocellular carcinoma(HCC)and adjacent tissues.These results suggest the regulatory role of circRNAs in SG formation and provide insights into the biological function of circRNAs and SGs in HCC.

Dysregulation of circular RNAs in inflammation and cancers

Emerging lines of evidence have shown that the production of the covalently closed single-stranded circular RNAs is not splicing errors,but rather a regulated process with distinct biogenesis and turnover.Circular RNAs are expressed in a cell type-and tissue-specific manner and often localize to specific subcellular regions or organelles for functions.The dysregulation of circular RNAs from birth to death is linked to the pathogenesis and progression of diverse diseases.This review outlines how aberrant circular RNA biogenesis,subcellular location,and degradation are linked to disease progression,focusing on metaflammation and cancers.We also discuss potential therapeutic strategies and obstacles in targeting such disease-related circular RNAs.

微生物组测序与分析专家共识

在过去的十几年,微生物组相关研究和应用持续升温。微生物组逐渐成为生命科学、环境科学和医学等领域的研究焦点。与此同时,全球多个国家和组织也都积极发起各自的微生物组计划,进行多方面的布局,力争在这一具有广阔前景的领域获得战略地位。此外,无论是科研还是产业应用已经迎来了研究高潮和投融资热潮,微生物组相关产品和服务也不断出现。然而,行业在快速发展的同时,也存在一些不足。由于微生物组测序和分析相关技术和方法发展迅速,各国研究和应用尚未在技术、方案和数据等标准上达成统一,国内行业参与者对微生物组也存在认识不足,对微生物组相关新方法、新技术、新理论等还未能充分掌握和使用。除此之外,已有的一些标准和指南,内容过于简单,实操性也不足,这不仅给科研数据的整合造成了困难和资源浪费,还给相关企业进行不良竞争、以次充好提供了机会。更重要的是,我国尚缺乏微生物组相关的国家标准,国家微生物组计划仍处于筹备过程。在此背景下,中国生物工程学会、中国科学院微生物研究所于2019年6月至2020年3月,共同设立了“微生物组测序与分析专家共识”专项研究课题。中国生物工程学会组织了微生物组相关领域的27位专家以及来自行业内的30多位专业人员,通过分成4个项目小组、召开4轮研讨会后,最终形成了涵盖从微生物采集与保存、DNA提取与建库、高通量基因测序和数据分析以及质控标准品等全流程的“微生物组测序与分析专家共识”。本专家共识具有较强可参考性和可操作性,不仅能指导国内科研和产业机构规范进行微生物组相关产、学、研,还能为国家相关职能部门提供可参考的技术依据,保障规模型和规范化的企业利益,加强行业自律,避免不规范的企业扰乱市场,最终促进微生物组相关产业的良性发展。

Single-cell metagenomics： challenges and applications

With the development of high throughput sequencing and single-cell genomics technologies, many uncultured bacterial communities have been dissected by combining these two techniques. Especially, by simul- taneously leveraging of single-cell genomics and metagenomics, researchers can greatly improve the efficiency and accuracy of obtaining whole genome information from complex microbial communities, which not only allow us to identify microbes but also link function to species, identify subspecies variations, study host-virus interactions and etc. Here, we review recent developments and the challenges need to be addressed in single-cell metagenomics, including potential contamination, uneven sequence coverage, sequence chimera, genome assembly and annotation. With the development of sequencing and computational methods, single-cell metagenomics will undoubtedly broaden its application in various microbiome studies.

Small RNA transcriptome investigation based on next-generation sequencing technology

Over the past decade, there has been a growing realization that studying the small RNA transcriptome is essential for understanding the complexity of transcriptional regulation. With an increased throughput and a reduced cost, next-generation sequencing technology has provided an unprecedented opportunity to measure the extent and complexity of small RNA transcriptome. Meanwhile, the large amount of obtained data and varied technology platforms have also posed multiple challenges for effective data analysis and mining. To provide some insight into the small RNA transcriptome investigation, this review describes the major small RNA classes, experimental methods to identify small RNAs, and available bioinformatics tools and databases.

Phylogenomics of non-model ciliates based on transcriptomic analyses

Ciliates are one of the oldest living eukaryotic unicellular organisms, widely distributed in the waters around the world. As a typical marine oligotrich ciliate, Strombidium sulcatum plays an important role in marine food webs and energy flow. Here we report the first deep se- quencing and analyses of RNA-Seq data from Strombidium sulcatum. We generated 42,640 unigenes with an N50 of 1,451 bp after de novo assembly and removing rRNA, mitochondrial and bacteria contaminants. We employed SPOCS to detect orthologs from S. sulcatum and 17 other ciliates, and then carried out the phyloge- nomic reconstruction using 127 single copy orthologs. In phylogenomic analyses, concatenated trees have similar topological structures with concordance tree on the class level. Together with phylogenetic networks analysis, it aroused more doubts about the placement of Protocruzia, Mesodinium and Myrionecta. While epi- plasmic proteins are known to be related to morphological characteristics, we found the potential relationship between gene expression of epiplasmic proteins and morphological characteristics. This work supports the use of high throughput approaches for phylogenomic analysis as well as correlation analysis between expression level of target genes and morphological characteristics.

Microbiota-gut-brain axis in autism spectrum disorder

Extensive studies, largely during the past decade, identify the dynamic and bidirectional interaction between the bacteria resident in the intestines and their host brain along the "microbiota-gut-brain axis". This interaction modulates the development and function of the central nervous system and is implicated in neurological disorders. As a neurodevelopmental disorder, autism spectrum disorder (ASD) is considered a historically defect in the brain. With accumulating evidence showing how the microorganisms modulate neural activities, more and more research is focusing on the role of the gut microbiota in mitigating ASD symptoms and the underlying mechanisms. In this review, we describe the intricate and crucial pathways via which the gut microbiota communicates with the brain, the microbiota-gut-brain axis, and summarize the specific pathways that mediate the crosstalk of the gut microbiota to the brain in ASD.

Variation of the Vaginal Microbiome During and After Pregnancy in Chinese Women

A comprehensive profiling of the vaginal microbial communities and their variability enables an accurate description of the microbiome in women.However,there is a lack of studies available on Chinese women.In the present study,the composition of the vaginal microbiota during pregnancy and the 6-week postpartum period of 454 Chinese women was characterized by sequencing the V3-V4 region of the 16S ribosomal RNA(rRNA)gene.The vaginal microbiome showed variations during pregnancy and the postpartum period based on the abortion history,hypertensive disorders,delivery mode,and maternal age.Co-variation of 22 bacterial taxa,including the Lactobacillus genus and two of its species,may account for the common characteristics of the vaginal microbiome under scenarios of different medical histories and pregnancy outcomes.In contrast,discriminant bacterial species were significantly different between women who had preterm birth(PTB)with and without premature rupture of membranes(PROM),and the community state type(CST)IV-A without any predominant Lactobacillus species in the microbiota was more prevalent during pregnancy in the PROM-PTB cases,suggesting that specific bacterial species could be considered to distinguish between different types of PTB.By providing data on Chinese women,this study will enrich the knowledge of the human microbiome and contribute to a better understanding of the association between the vaginal microbiome and reproductive health.

The first metagenome of activated sludge from full-scale anaerobic/anoxic/oxic(A2O) nitrogen and phosphorus removal reactor using Illumina sequencing

The anaerobic/anoxic/oxic（A2O） process is globally one of the widely used biological sewage treatment processes. This is the first report of a metagenomic analysis using Illumina sequencing of full-scale A2O sludge from a municipal sewage treatment plant.With more than 530,000 clean reads from different taxa and metabolic categories, the metagenome results allow us to gain insight into the functioning of the biological community of the A2O sludge. There are 51 phyla and nearly 900 genera identified from the A2O activated sludge ecosystem. Proteobacteria, Bacteroidetes, Nitrospirae and Chloroflexi are predominant phyla in the activated sludge, suggesting that these organisms play key roles in the biodegradation processes in the A2O sewage treatment system.Nitrospira, Thauera, Dechloromonas and Ignavibacterium, which have abilities to metabolize nitrogen and aromatic compounds, are most prevalent genera. The percent of nitrogen and phosphorus metabolism in the A2O sludge is 2.72% and 1.48%, respectively. In the current A2O sludge, the proportion of Candidatus Accumulibacter is 1.37%, which is several times more than that reported in a recent study of A2O sludge. Among the four processes of nitrogen metabolism, denitrification related genes had the highest number of sequences（76.74%）, followed by ammonification（15.77%）, nitrogen fixation（3.88%） and nitrification（3.61%）. In phylum Planctomycetes, four genera（Planctomyces, Pirellula, Gemmata and Singulisphaera） are included in the top 30 abundant genera, suggesting the key role of ANAMMOX in nitrogen metabolism in the A2O sludge.

Characterization of human αβTCR repertoire and discovery of D-D fusion in TCRβ chains

The characterization of the human T-cell receptor （TCR） repertoire has made remarkable progress, with most of the work focusing on the TCRβ chains. Here, we ana- lyzed the diversity and complexity of both the TCRa and TCRβ repertoires of three healthy donors. We found that the diversity of the TCRα repertoire is higher than that of the TCRβ repertoire, whereas the usages of the V and J genes tended to be preferential with similar TRAV and TRAJ patterns in all three donors. The V-J pairings, like the V and J gene usages, were slightly preferential. We also found that the TRDV1 gene rearranges with the majority of TRAJ genes, suggesting that TRDV1 is a shared TRAV/DV gene （TRAV42/DV1）. Moreover, we uncovered the presence of tandem TRBD （TRB D gene） usage in -2% of the productive human TCRβ CDR3 sequences.

Precision Medicine:What Challenges Are We Facing?

Following the publication of the US National Research Council （N RC） report ＂ Toward PrecMon Medicine.＂ Building a Knowledge Network for Biomedical Research and a New Taxonomy of Diseases＂ in 2011 [1], several nations have announced that their national research programs would definitely head toward this direction. Now,

Maternal and neonatal viromes indicate the risk of offspring's gastrointestinal tract exposure to pathogenic viruses of vaginal origin during delivery

A cumulative effect of enterovirus and gluten intake on the risk of celiac disease autoimmunity in infants highlights the significance of viral exposure in early life on the health of children.However,pathogenic viruses may be transmitted to the offspring in an earlier period,raising the possibility that women whose vaginas are inhabited by such viruses may have had their babies infected as early as the time of delivery.A high‐resolution intergenerational virome atlas was obtained by metagenomic sequencing and virome analysis on 486 samples from six body sites of 99 mother–neonate pairs.We found that neonates had less diverse oral and enteric viruses than mothers.Vaginally delivered newborns seconds after birth had a more similar oral virome and more viruses of vaginal origin than cesarean‐section(C‐section)newborns(56.9%vs.5.8%).Such viruses include both Lactobacillus phage and potentially pathogenic viruses,such as herpesvirus,vaccinia virus,and hepacivirus,illustrating a relatively high variety of the pioneer viral taxa at the time of delivery and a delivery‐dependent mother‐to‐neonate transmission along the vaginal–oral–intestinal route.Neonates are exposed to vaginal viruses as they pass through the reproductive tract,and viruses of vaginal origin may threaten their health.These findings challenge the conventional notion that vaginal delivery is definitely better than cesarean delivery from the perspective of microbial transmission.Screening for vaginal virome before delivery is a worthwhile step to advocate in normal labor to eliminate the risk of intergenerational transmission of pathogenic viruses to offspring.

First Glimpse of Gut Microbiota of Quarantine Insects in China

Quarantine insects are economically important pests that frequently invade new habitats.A rapid and accurate monitoring method to trace the geographical sources of invaders is required for their prevention,detection,and eradication.Current methods based on genetics are typically time-consuming.Here,we developed a novel tracing method based on insect gut microbiota.The source location of the insect gut microbiota can be used to rapidly determine the geographical origin of the insect.We analyzed 179 gut microbiota samples from 591 individuals of 22 quarantine insect species collected from 36 regions in China.The gut microbiota of these insects primarily included Actinobacteria,Bacteroidetes,Cyanobacteria,Firmicutes,Proteobacteria,and Tenericutes.The diversity of the insect gut microbiota was closely associated with geographical and environmental factors.Different insect species could be distinguished based on the composition of gut microbiota at the phylum level.Populations of individual insect species from different regions could be distinguished based on the composition of gut microbiota at the phylum,class,and order levels.A method for determining the geographical origins of invasive insect species has been established;however,its practical application requires further investigations before implementation.

MBRidge: an accurate and cost-effective method for profiling DNA methylome at single-base resolution

Organisms and cells,in response to environmental influences or during development,undergo considerable changes in DNA methylation on a genome-wide scale,which are linked to a variety of biological processes.Using MethylC-seq to decipher DNA methylome at single-base resolution is prohibitively costly.In this study,we develop a novel approach,named MBRidge,to detect the methylation levels of repertoire CpGs,by innovatively introducing C-hydroxylmethylated adapters and bisulfate treatment into the MeDIP-seq protocol and employing ridge regression in data analysis.A systematic evaluation of DNA methylome in a human ovarian cell line T29 showed that MBRidge achieved high correlation(R>0.90)with much less cost(∼10%)in comparison with MethylC-seq.We further applied MBRidge to profiling DNA methylome in T29H,an oncogenic counterpart of T29’s.By comparing methylomes of T29H and T29,we identified 131790 differential methylation regions(DMRs),which are mainly enriched in carcinogenesis-related pathways.These are substantially different from7567 DMRs that were obtained by RRBS and related with cell development or differentiation.The integrated analysis ofDMRsin the promoterand expression of DMR-corresponding genes revealed thatDNAmethylation enforced reverse regulation of gene expression,depending on the distance fromthe proximalDMRto transcription starting sites in both mRNA and lncRNA.Taken together,our results demonstrate that MBRidge is an efficient and cost-effective method that can be widely applied to profiling DNA methylomes.

An efficient metatranscriptomic approach for capturing RNA virome and its application to SARS-CoV-2

Coronavirus disease 2019(COVID-19)is a new type of respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which has caused severe social and economic costs and has become a great threat to public health because of the high mortality rate.Recent studies indicated that respiratory pathogens co-infection and secondary infection were critical risk factors for the severity and mortality rates of COVID-19(Zhou et al.,2020).

Bioinformatics Commons: The Cornerstone of Life and Health Sciences

Bioinformatics, an interdisciplinary field that combines biology, mathematics, computer science, medicine, and health science, to integrate, analyze, and interpret biological data, is now becoming increasingly data-intensive. To dig out the treasure from big data powered by high-throughput sequencing technologies, it is highly dependent on Bioinformaties Commons that involves a variety of fundamental resources, includ- ing databases, web servers, algorithms, methods, software tools, ontologies, and standards. To be short, Bioinformatics Commons has become the cornerstone of life and health sciences, facilitating and accelerating the translation of big data into big discoveries.

The Value and Significance of Metagenomics of Marine Environments

Microbes have played a fundamental role in the natural his- tory of our planet, and have done so for billions of years. They have adapted to Earth＇s many environments from the mild to the very extreme. Studying their diversity and their way of life is critical for understanding their full impact on the global ecology. Although the field of metagenomics is still young, it has unravelled a wider microbial diversity that had otherwise been completely overlooked by the traditional methods of microbiology. There are three major metagenomic themes： （a） marker metagenomics that surveys microbial community structure by targeting the highly-conserved 16S rRNA gene, （b） functional metagenomics that takes the total environmental DNA, from which it infers the metabolic potential of the microbial community, and （c） identification of novel enzymes.