Metagenomics revealing molecular profiles of microbial community structure and metabolic capacity in Bamucuo lake, Tibet.

Microorganisms play critical ecological roles in the global biogeochemical cycles. However, extensive information on the microbial communities in Qinghai-Tibet Plateau (QTP), which is the highest plateau in the world, is still lacking, particularly in high elevation locations above 4500 m. Here, we performed a survey of th e soil and water microbial communities in Bamucuo Lake, Tibet, by using shotgun metagenomic methods. In the soil and water samples, we reconstructed 75 almost complete metagenomic assembly genomes, and 74 of the metagenomic assembly genomes from the water sample represented novel species. Proteobacteria and Actinobacteria were found to be the dominant bacterial phyla, while Euryarchaeota was the dominant archaeal phylum. The largest virus, Pandoravirus salinus, was found in the soil microbial community. We concluded that the microorganisms in Bamucuo Lake are most likely to fix carbon mainly through the 3-hydroxypropionic bi-cycle pathway. This study, for the first time, characterized the microbial community composition and metabolic capacity in QTP high-elevation locations with 4555 m, confirming that QTP is a vast and valuable resource pool, in which many microorganisms can be used to develop new bioactive substances and new antibiotics to which pathogenic microorganisms have not yet developed resistance.

Molecular evolutionary characteristics of SARS-CoV-2 emerging in the United States.

SARS-CoV-2 is a newly discovered beta coronavirus at the end of 2019, which is highly pathogenic and poses a serious threat to human health. In this paper, 1875 SARS-CoV-2 whole genome sequences and the sequence coding spike protein (S gene) sampled from the United States were used for bioinformatics analysis to study the molecular evolutionary characteristics of its genome and spike protein. The MCMC method was used to calculate the evolution rate of the whole genome sequence and the nucleotide mutation rate of the S gene. The results showed that the nucleotide mutation rate of the whole genome was 6.677 × 10-4 substitution per site per year, and the nucleotide mutation rate of the S gene was 8.066 × 10-4 substitution per site per year, which was at a medium level compared with other RNA viruses. Our findings confirmed the scientific hypothesis that the rate of evolution of the virus gradually decreases over time. We also found 13 statistically significant positive selection sites in the SARS-CoV-2 genome. In addition, the results showed that there were 101 nonsynonymous mutation sites in the amino acid sequence of S protein, including seven putative harmful mutation sites. This paper has preliminarily clarified the evolutionary characteristics of SARS-CoV-2 in the United States, providing a scientific basis for future surveillance and prevention of virus variants.

Machine learning revealed molecular classification of colorectal cancer with negative lymph node metastasis.

Purpose: Accurate preoperative staging directly affects the treatment decision of patients with rectal cancer. However, our understanding of the immune subclasses of CRC without lymph node metastasis is still incomplete.Materials and methods: Here, we first analyzed the subclasses of CRC without lymph node metastasis on the Cancer Genome Atlas (TCGA) and verified its stability in the GSE39582 dataset. Four immune subclasses (C1-C4) were identified and verified by non-negative matrix factorization (NMF) of gene expression profiles. Then, ICI scores of six genes were constructed to characterize subclasses.Results: There were significant differences in metabolic and progression-associated signatures, immune characteristics, and clinical characteristics among subclasses. C3 represented a good prognosis with high TMB. C4 showed unique immune characteristics. We believe that C3 is the initial stage of CRC. After the C1 and C2 stages, it progresses to the C4 stage, and finally, lymph node metastasis occurs.Conclusions: This work may help to provide a basis for immunotherapy decision-making in early CRC and may guide personalized methods of cancer immunotherapy.

Transcriptome profiling analysis of sex-based differentially expressed mRNAs and lncRNAs in the brains of mature zebrafish (Danio rerio).

BACKGROUND: Similar to humans, the zebrafish brain plays a central role in regulating sexual reproduction, maturation and sexual behavior. However, systematic studies of the dimorphic patterns of gene expression in the brain of male and female zebrafish are lacking. RESULTS: In this study, the mRNA and lncRNA expression profiles were obtained from the brain tissue samples of the three male and three female zebrafish by high-throughput transcriptome sequencing. We identified a total of 108 mRNAs and 50 lncRNAs with sex-based differential expression. We randomly selected four differentially expressed genes for RT-qPCR verification and the results certified that the expression pattern showed a similar trend between RNA-seq and RT-qPCR results. Protein-protein interaction network analysis, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to obtain the biological significance of differentially expressed mRNA in the brain dimorphism of zebrafish. Finally, a Pearson correlation analysis was performed to construct the co-expression network of the mRNAs and lncRNAs. CONCLUSIONS: We found that 12 new lncRNAs not only have significant gender specificity in the brain of zebrafish, and this finding may provide a clue to further study of the functional difference between male and female zebrafish brain.

Comprehensive analysis of lncRNA-associated ceRNA network in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies and morbidity and mortality are increasing rapidly. Increasing evidence showed the close correlation between aberrant expression of certain RNAs and the occurrence and development of CRC. However, comprehensive analyses of differentially expressed profiles of linRNA in CRC based on large sample size have been lacking. In the present study, based on RNA-seq data obtained from the TCGA (The Cancer Genome Atlas) database, we identified 1176 lncRNAs, 245 miRNAs and 2083 mRNAs whichaberrantly expressed in the colorectal cancer tissues compared with the adjacent non-tumorous tissues. A Kaplan-Meier curve analysis was used to study the overall survival rate of the three RNA-related CRC patients. After constructing the ceRNA network, we performed the KEGG enrichment pathway analysis on ceRNA-related differentially expressed mRNAs and found that these mRNAs were remarkably enriched in the pathways associated with CRC. Combining the differentially expressed lncRNAs with clinical pathological variables of CRC patients, we also found that LINC00400 and LINC00355 not only contribute to the regulation of ceRNA network, but also show significantchanges in its expression in multiple CRC pathological stages, indicating that LINC00400 and LINC00355 can be considered as promising therapeutic targets for CRC.

Clarifying real receptor binding site between coronavirus HCoV-HKU1 and 9-O-Ac-Sia based on molecular docking.

HCoV-HKU1 is a [Formula: see text]-coronavirus with low pathogenicity, which usually leads to respiratory diseases. At present, a controversial issue is that whether the receptor binding site (RBS) of HCoV-HKU1 is located in the N-terminal domain (NTD) or the C-terminal domain (CTD) in the HCoV-HKU1 S protein. To address this issue, we used molecular docking technology to dock the NTD and CTD with 9-oxoacetylated sialic acid (9-O-Ac-Sia), respectively, with the results showing that the RBS of HCoV-HKU1 is located in the NTD (amino acid residues 80-95, 25-32). Our findings clarified the structural basis and molecular mechanism of the HCoV-HKU1 infection, providing important information for the development of therapeutic antibody drugs and the design of vaccines.

Prognostic value of immune scores in the microenvironment of colorectal cancer.

Cancer immunotherapy has become an important means of cancer treatment; however, the complex composition and heterogeneity of the colorectal cancer (CRC) microenvironment pose a huge challenge to cancer immunotherapy. Using data downloaded from The Cancer Genome Atlas database, the differences in the microenvironment between cases with low and high immune scores were examined at the multiomics level using bioinformatics approaches. It was revealed that the samples with high immune scores had good cytolytic immune responses and relatively abundant stromal cells, as well as significant infiltration of 22 immune cell subsets and a high non-synonymous mutation burden and neoantigen burden. All of these characteristics contribute to a good prognosis. To better understand the impact of immune-related genes on prognosis, differentially expressed genes between the low and high immune score samples were identified and it was concluded that serpin family Emember 1 (SERPINE1) and ubiquitin C-terminal hydrolase L1 (UCHL1) may be potential therapeutic targets. The relationship between the immune score and the infiltration of 22 immune cells and the difference in SERPINE1 expression were verified by analyzing the GSE17536 and GSE21510 data sets downloaded from the Gene Expression Omnibus database. The present study analyzed the unique properties of immune cells in the CRC microenvironment, which are of great significance for understanding CRC immune mechanism and may also provide novel ideas for the targeted design of cancer immunotherapy.

Low mutation burden and differential tumor-infiltrating immune cells correlate with lymph node metastasis in colorectal cancer.

BACKGROUND: Tumor immunotherapy has become an important means of cancer treatment. A response depends on the interaction of tumor cells with immune regulators in the tumor microenvironment, which plays an important role in inhibiting or enhancing the immune response. However, lymph node (LN) metastasis leads to major changes in the tumor microenvironment of patients with colorectal cancer, directly affecting prognosis. METHODS: Using data downloaded from the Cancer Genome Atlas (TCGA) database, we studied the microenvironmental differences between LN-negative and positive populations by bioinformatic methods. RESULTS: Patients in the LN-positive group had significantly lower immune scores, cytolytic activity scores, and overall survival than the LN-negative group. In addition, a high mutation burden and a new antigen burden could inhibit lymph node metastasis of CRC. In particular, in the LN positive group, the ratio of monocytes to M1 macrophages was significantly downregulated. After the differentially expressed mRNAs between the LN positive and negative groups were determined, a new CRC model was constructed based on multivariate Cox proportional hazard regression analysis to examine the prognosis of patients. The analyses showed that the model was stable and robust. CONCLUSIONS: We used multiple scores and details of immune cell infiltration as indicators to assess changes in the tumor microenvironment of CRC patients before and after lymph node metastasis, and quantify and model the immune cells in the microenvironment to predict the overall survival of CRC patients.

Identification of key lncRNAs as prognostic prediction models for colorectal cancer based on LASSO.

Colorectal cancer (CRC) is one of the most common malignancies, with varying prognoses and a high mortality. There is an urgent need to establish a new prediction model to predict the survival risk of CRC patients. The long non-coding RNAs (lncRNAs) expression profiles and corresponding clinical information of CRC patients were obtained from The Cancer Genome Atlas, TCGA. We identified a total of 1,176 lncRNAs differentially expressed between 480 CRC and 41 normal tissues. In the training test, we combined these differentially expressed lncRNAs with overall survival of CRC patients. Six lncRNAs (AL356270.1, LINC02257, AC020891.2, LINC01485, AC083967.1 and RBAKDN) were finally screened out by using LASSO regression mode to establish a novel prediction model as a prognostic indicator for CRC patients. The area under the curve (AUC) of 3- and 5-year ROC analysis in CRC were 0.6923 and 0.7328 for training set, and were 0.6803 and 0.7035 for testing set, respectively. K-M analysis revealed a significant difference between high risk and low risk in the training set (P-value = 5.0e-05) and testing set (P-value = 0.00052), respectively. Our study shows that the six lncRNAs model can improve the survival prediction mechanism of patients with CRC and provide help for patients through personalized treatment.

Prognostic value of miR-21 in gliomas: comprehensive study based on meta-analysis and TCGA dataset validation.

Recent studies have highlighted the value of microRNA-21 (miR-21) as a prognostic biomarker in gliomas. However, the role of miR-21 in predicting prognosis remains controversial. We performed a comprehensive study based upon a meta-analysis and The Cancer Genome Atlas (TCGA) glioma dataset validation to clarify the prognostic significance of miR-21 in glioma patients. In this study, we searched Embase, PubMed, Web of science, CNKI, SinoMed, and Wanfang databases for records up to May 2018. Relevant data were extracted to assess the correlation between miR-21 expression and survival in glioma patients. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to describe association strength. We further used multivariate Cox regression analysis to assess miR-21 expression in the TCGA glioma dataset to validate the relationship between miR-21 expression and survival. Nine studies were included in the meta-analysis. Among them, eight studies provided data on overall survival (OS) with a pooled HR of 1.91 (95% CI: 1.34, 2.73), indicating that higher expression of miR-21 was significantly associated with worse OS in glioma patients; for the other study, which provided data on progression-free survival (PFS), no statistically significant HR was reported for PFS in the glioma patients (HR = 1.23, 95% CI: 0.41, 3.72). A multivariate Cox regression analysis of the miR-21 expression in the TCGA glioma dataset revealed that overexpression of miR-21 was a potential independent prognostic biomarker of poorer OS (HR = 1.27, 95% CI: 1.01, 1.59) and poorer PFS (HR = 1.46, 95% CI: 1.17, 1.82). Our findings suggest that higher expression of miR-21 is correlated with poorer glioma prognosis.

Identification and meta-analysis of copy number variation-driven circadian clock genes for colorectal cancer.

Both copy number variation (CNV) and circadian clock genes play a critical role in the etiology and pathogenesis of colorectal cancer (CRC); however, a comprehensive analysis of CNV-driven circadian clock genes is urgently required. The present study aimed to investigate the systematic associations between somatic cell CNVs and circadian clock gene expression in patients with CRC. Using somatic CNV, legacy clinical information and gene expression data from The Cancer Genome Atlas, 295 genes that were significantly differentially expressed and with significantly different CNV were obtained, and the expression of the genes, among which 15 were circadian clock genes, was significantly associated with CNV. Further analysis revealed that aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) expression and CNV in these circadian clock genes were significantly associated with survival time in patients with CRC, and the expression of ARNTL2 was also significantly associated with the pathological stage of CRC. Gene set enrichment analysis found that ARNTL2 is enriched for gene sets associated with CRC pathogenesis such as the p53 signaling pathway. These results suggest that ARNTL2 may be a promising prognostic biomarker for patients with CRC, and that circadian clock genes play an important role in CRC through CNV.

Identification and characterization of circRNAs as competing endogenous RNAs for miRNA-mRNA in colorectal cancer.

BACKGROUND: Recent studies showed that circRNAs are involved in the biological process of some human cancers. However, little is known about their functions in colorectal cancer (CRC). METHODS: Here we first revealed the expression profiles of circRNAs in the CRC tissues and the adjacent non-tumorous tissues using high-throughput sequencing. The sequence feature, chromosome location, alternative splicing and other characteristics of the circRNAs were also explored. The miRNA and mRNA expression profiles were then obtained by analyzing relevant CRC data retrived from the TCGA database. We obtained and analyzed the competing endogenous RNA (ceRNA) network of the top three pairs of the largest up-regulated and down-regulated circRNAs. RESULTS: In this study, we obtained 50,410 circRNAs in the CRC tissue and the adjacent non-tumor tissues, of which 33.7% (16,975) were new, and revealed differential changes in circRNA expression during colorectal carcinogenesis. We have identified six potential key circRNAs (circPIEZO1-3, hsa_circ_0067163, hsa_circ_0140188, hsa_circ_0002632, hsa_circ_0001998 and hsa_circ_0023990) associated with CRC, which play important roles in carcinogenesis as ceRNA for regulation of miRNA-mRNA network. In the subsequent KEGG analysis, several CRC-related pathways were found. CONCLUSIONS: Our findings advance the understanding of the pathogenesis of CRC from the perspective of circRNAs and provide some circRNAs as candidate diagnostic biomarkers or potential therapeutic targets.