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2.
Nat Methods ; 21(2): 259-266, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38049696

ABSTRACT

Small extracellular vesicles (sEVs) are emerging as pivotal players in a wide range of physiological and pathological processes. However, a pressing challenge has been the lack of high-throughput techniques capable of unraveling the intricate heterogeneity of sEVs and decoding the underlying cellular behaviors governing sEV secretion. Here we leverage droplet-based single-cell RNA sequencing (scRNA-seq) and introduce an algorithm, SEVtras, to identify sEV-containing droplets and estimate the sEV secretion activity (ESAI) of individual cells. Through extensive validations on both simulated and real datasets, we demonstrate SEVtras' efficacy in capturing sEV-containing droplets and characterizing the secretion activity of specific cell types. By applying SEVtras to four tumor scRNA-seq datasets, we further illustrate that the ESAI can serve as a potent indicator of tumor progression, particularly in the early stages. With the increasing importance and availability of scRNA-seq datasets, SEVtras holds promise in offering valuable extracellular insights into the cell heterogeneity.


Subject(s)
Extracellular Vesicles , Neoplasms , Humans , Transcriptome , Algorithms
3.
Gut Microbes ; 14(1): 2100197, 2022.
Article in English | MEDLINE | ID: mdl-35854629

ABSTRACT

Fecal microbiota transplantation (FMT) is a promising treatment for microbiota dysbiosis associated diseases, such as Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD). The engraftment of donor bacteria is essential for the effectiveness of FMT, which to some extent depends on the matching of donors and recipients. However, how different types of donor-derived bacteria affect FMT efficacy has not been fully dissected. We recruited two longitudinal IBD cohorts of 103 FMT recipients and further analyzed 1,280 microbiota datasets from 14 public CDI and IBD studies to uncover the effect of donor-derived microbiota in recipients. We found that two enterotypes, RCPT/E and RCPT/B (dominated by Enterobacteriaceae and Bacteroides, respectively), consistently exist in both CDI and IBD patients. Based on a time-course-based multi-cohort analysis of FMT fecal samples, we observed the interplay between recipient and donor-derived microbiota during FMT, in which the FMT outcome was significantly associated with the enterotype and microbiota distance between donor and recipient after FMT. We proposed a new measurement, the ratio of colonizers to residents after FMT (C2R), to quantify the engraftment of donor-derived bacteria in the recipients, and then constructed an enterotype-based statistical model for donor-recipient matching, which was validated by both cross-validation and an additional IBD FMT cohort (n = 42). We believe that with the accumulation of FMT multi-omics datasets, machine learning-based methods will be helpful for rational donor selection for improving efficacy and precision FMT practices.


Subject(s)
Clostridioides difficile , Clostridium Infections , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Bacteria/genetics , Clostridium Infections/microbiology , Fecal Microbiota Transplantation/methods , Feces/microbiology , Humans , Inflammatory Bowel Diseases/microbiology , Treatment Outcome
4.
Front Microbiol ; 10: 1579, 2019.
Article in English | MEDLINE | ID: mdl-31354673

ABSTRACT

Large-scale campus resembles a small "semi-open community," harboring disturbances from the exchanges of people and vehicles, wherein stressors such as temperature and population density differ among the ground surfaces of functional partitions. Therefore, it represents a special ecological niche for the study on microbial ecology in the process of urbanization. In this study, we investigated outdoor microbial communities in four campuses in Wuhan, China. We obtained 284 samples from 55 sampling sites over six seasons, as well as their matching climatic and environmental records. The structure of campus outdoor microbial communities which influenced by multiple climatic factors featured seasonality. The dispersal influence of human activities on microbial communities also contributed to this seasonal pattern non-negligibly. However, despite the microbial composition alteration in response to multiple stressors, the overall predicted function of campus outdoor microbial communities remained stable across campuses. The spatial-temporal dynamic patterns on campus outdoor microbial communities and its predicted functions have bridged the gap between microbial and macro-level ecosystems, and provided hints toward a better understanding of the effects of climatic factors and human activities on campus micro-environments.

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