Biology subjects

Gao, N. L.

Publications and source records attributed to Gao, N. L..

5 recordsLinked to original sources

bioRxiv2023

Long-read sequencing reveals extensive DNA methylations in human gut phagenome contributed by prevalently phage-encoded methyltransferases

DNA methylation is essential for the survival of bacteriophages (phages), yet, we know little about the methylation of their genomes. Here, we analyze the DNA methylation patterns of 8,848 metagenome-assembled high-quality phages across 104 fecal samples using single-molecule real-time (SMRT) sequencing. We show that 97.60% of gut phages could be methylated, and reveal factors that correlate with methylation densities. Phages having higher methylation densities are more prevent, suggesting putative viability advantages of the DNA methylation. Strikingly, more than a third of the phages encode their own DNA methyltransferases (MTases). More MTase copies are associated with increased genome methylation densities, methylation motifs, and higher prevalence of certain phage groups. Most MTases are closely homologous to gut bacterium-encoded ones, likely exchanged during phage-bacterium interactions, and could be used to accurately predict phage-host relationships. Taken together, our results suggest that the gut DNA phages universally use DNA methylation to escape from host defense systems with significant contribution from phage-encoded MTases.

bioinformatics↗

bioRxiv2022

Vast human gut virus diversity uncovered by combined short- and long-read sequencing

Current metagenome-assembled human phage catalogs contained mostly fragmented genomes. Here, we developed a vigorous phage detection method involving phage enrichment and long-read sequencing and applied to 135 fecal samples. With ~10 times more efficient in obtaining complete genomes (~34%) than the Gut Virome Database, we identified the first megabasephage (~1.03Mb), and revealed the hidden diversity of the gut phageome including dozens of phages more prevalent than the crAssphages and Gubaphages.

bioinformatics↗

bioRxiv2020

Alterations of human lung and gut microbiome in non-small cell lung carcinomas and distant metastasis

BackgroundNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although dysbiosis of lung and gut microbiota have been associated with NSCLC, their relative contributions are unclear; in addition, their roles in distant metastasis (DM) are still illusive. ResultsWe surveyed the fecal and sputum (as a proxy for lung) microbiota in healthy controls and NSCLC patients of various stages, and found significant perturbations of gut- and sputum-microbiota in patients with NSCLC and DM. Machine-learning models combining both microbiota (mixed models) performed better than either dataset in patient stratification, with the highest area under the curve (AUC) value of 0.842. Sputum-microbiota contributed more than the gut in the mixed models; in addition, sputum-only models performed similarly to the mixed models in most cases. Several microbial-biomarkers were shared by both microbiota, indicating their similar roles at distinct body sites. Microbial-biomarkers of distinct disease stages were mostly shared, suggesting biomarkers for distant metastasis could be acquired early. Furthermore, Pseudomonas aeruginosa, a species previously associated with wound infections, was significantly more abundant in brain metastasis, indicating distinct types of DMs could have different microbial-biomarkers. ConclusionOur results indicate that alterations of sputum-microbiota have stronger relationships with NSCLC and distant metastasis than the gut, and strongly support the feasibility of metagenome-based non-invasive disease diagnosis and risk evaluation.

microbiology↗

bioRxiv2018

Consistent alterations of human fecal microbes after transplanted to germ-free mice

Fecal microbiota transplant (FMT) of human fecal samples to germ-free (GF) mice is useful for establishing causal relationships between altered gut microbiota and human phenotypes. However, due to intrinsic differences between human and mouse intestines, and distinct diets of choice between the two organisms, replicating human phenotypes in mouse through FMT is not guaranteed; similarly, treatments that are effective in mouse models do not guarantee their success in human either. In this study, we aimed to identify human gut microbes that have undergone significant and consistent changes after transplanted to GF mice across multiple experimental settings. By comparing gut microbiota profiles in 1,713 human-mouse pairs, we found strikingly on average <50% of the human gut microbes can be re-established in mice at the species level; among which, more than 1/3 have undergone significant changes (referred as to \"variable microbes\"), most of which were consistent across multiple human-mouse pairs and experimental settings. Consistently, one-third of human samples had changed their enterotypes, i.e. significant changes in their leading species after FMT. Mice fed with controlled diet showed significant decrease in the enterotype change rate (~25%) as compared those with non-controlled diet (~50%), suggesting a possible solution for rescue. Strikingly, most of the variable microbes have been implicated in human diseases, with some being recognized as causing species. Our results highlighted the challenges of using mouse model in replicating human gut microbiota-associated phenotypes, provided useful information for researchers using mice in their gut microbiota studies and call for additional validations after FMT.

bioinformatics↗

bioRxiv2018

Prokaryotic genome expansion is facilitated by phages and plasmids but impaired by CRISPR

Bacteriophages and plasmids can introduce novel DNA into bacterial cells, thereby creating an opportunity for genome expansion; conversely, CRISPR, the prokaryotic adaptive immune system, which targets and eliminates foreign DNAs, may impair genome expansions. Recent studies presented conflicting results over the impact of CRISPR on genome expansion. In this study, we assembled a comprehensive dataset of prokaryotic genomes and identified their associations with phages and plasmids. We found that genomes associated with phages and/or plasmids were significantly larger than those without, indicating that both phages and plasmids contribute to genome expansion. Genomes were increasingly larger with increasing numbers of associated phages or plasmids. Conversely, genomes with CRISPR systems were significantly smaller than those without, indicating that CRISPR has a negative impact on genome size. These results confirmed that on evolutionary timescales, bacteriophages and plasmids facilitate genome expansion, while CRISPR impairs such a process in prokaryotes. Furthermore, our results also revealed that CRISPR systems show a strong preference for targeting phages over plasmids.

bioinformatics↗