bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Leke Project: raise awareness on vaginal health in Cameroon
Authors: Kenfack Josiane 
Published: September 2024

Research on vaginal microbiome is expanding worldwide. Increasingly, research is being directed towards remote countries or communities where microbiome data were previously non-existent, and this is sometimes accompanied by challenges in communication, recruiting participants, collecting samples, and even transporting and storing these samples. The Leke project is an Isala sister project carried out in Cameroon which aims to map the vaginal microbiome of healthy women and break the taboo around vaginal health. Particularly in the Leke project, we raised awareness about vaginal health and healthy practices in remote communities by including in the conversation to men and women. In this presentation, we will explain the challenges we faced and how we overcame them to research the vaginal microbiome.Link to Josiane’s blog about the project: https://isala.be/en/the-leke-project-a-journey-to-the-isala-sister-project-in-cameroon/
Novel high-resolution targeted sequencing of the cervicovaginal microbiome
Authors: Molina Mariano A. 
Published: September 2024

The cervicovaginal microbiome (CVM) plays a significant role in women’s cervical health and disease. Microbial alterations at the species level and characteristic community state types (CST) have been associated with acquisition and persistence of high-risk human papillomavirus (hrHPV) infections that may result in progression of cervical lesions to malignancy. Current sequencing methods, especially most commonly used multiplex 16S rRNA gene sequencing, struggle to fully clarify these changes because they generally fail to provide sufficient taxonomic resolution to adequately perform species-level associative studies. To improve CVM species designation, we designed a novel sequencing tool targeting microbes at the species taxonomic rank and examined its potential for profiling the CVM. Results. We introduce an accessible and practical circular probe-based RNA sequencing (CiRNAseq) technology with the potential to profile and quantify the CVM. In vitro and in silico validations demonstrate that CiRNAseq can distinctively detect species in a mock mixed microbial environment, with the output data reflecting its ability to estimate microbes’ abundance. Moreover, compared to 16S rRNA gene sequencing, CiRNAseq provides equivalent results but with improved sequencing sensitivity. Analyses of a cohort of cervical smears from hrHPV-negative women versus hrHPV-positive women with high-grade cervical intraepithelial neoplasia confirmed known differences in CST occurring in the CVM of women with hrHPV-induced lesions. The technique also revealed variations in microbial diversity and abundance in the CVM of hrHPV-positive women when compared to hrHPV-negative women. Conclusions. CiRNAseq is a promising tool for studying the interplay between the CVM and hrHPV in cervical carcinogenesis. This technology could provide a better understanding of cervicovaginal CST and microbial species during health and disease, prompting the discovery of biomarkers, additional to hrHPV, that can help detect high-grade cervical lesions.Link to OA paper: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-021-01204-z
Topic models for interpretable multidomain microbiome data
Authors: Holmes Susan 
Published: September 2024

Data from sequencing bacterial communities are formalized as contingency tables whose columns correspond to different biological sample-specimens. The row-features are a random collection of Amplicon Sequence Variants (ASVs in the case of 16S rRNA type amplicon sequencing) or gene fragments (in the case of metagenomics). In both cases, these entities are defined after the data are collected, thus imposing a nonparametric framework. There are usually more features-rows than columns imposing necessary regularization through use of Bayesian priors.However, the classical Dirichlet-multinomial models are insufficient to account for the strong associations (or exclusions) between certain bacteria, thus recent hierarchical models such as latent Dirichlet topic models have provided a more flexible framework that allow mixed membership models more appropriate for these non-Gaussian data.We will show how these hierarchical topic models can enhance our understanding of both longitudinal dependencies between samples and biological dependencies between taxa, regardless of the differences in sampling depth and sources of variability.
This contains work with Kris Sankaran, Pratheepa Jeganathan, Laura Symul, Ben Callahan, and David Relman.
Not all stool is created equal: Strain engraftment competition and functional augmentation in a multi-donor faecal microbiota transplantation trial for obesity
Authors: Wilson Brooke 
Published: September 2024

Transplantation of faecal microbiota (FMT) from healthy lean donors has been shown to transiently improve insulin sensitivity and alter fat distribution in individuals with obesity and metabolic syndrome. However, the mechanisms and levels of donor strain engraftment required to elicit these effects remain poorly characterised. To address this, we performed a double-blinded randomised placebo-controlled trial for FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four healthy, lean, sex-matched donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. FMT capsules and recipient stool samples collected at baseline, 6-, 12- and 26-weeks post-treatment were analysed by shotgun metagenomic sequencing allowing us to track donor strain engraftment and monitor changes in the recipient gut microbiome over time. We found that multi-donor FMT sustainably altered the structure and functional potential of the gut microbiome for up to six months. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment. These ‘super-donor’ microbiomes were characterized by high microbial diversity and a high Prevotella to Bacteroides ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the microbiome, including pathways previously shown to be important in energy balance homeostasis (e.g. NAD biosynthesis). Despite our attempts to standardize FMT dose and donors, FMT recipients varied widely in their engraftment of donor strains suggesting the host environment plays a critical role in mediating FMT receptivity. Further work is required to better understand the various host-microbe interactions that determine engraftment success to help in developing more effective and personalised microbial therapies.Link to OA paper: https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-021-01060-7
Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease
Authors: Hoskinson Courtney 
Published: September 2024

Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may determine if tolerant immune pro- gramming arises within the infant. Here we show, using deeply phenotyped participants in the CHILD birth cohort (n = 1115), that there are early-life influences and microbiome features which are uniformly associated with four distinct allergic diagnoses at 5 years: atopic dermatitis (AD, n = 367), asthma (As, n = 165), food allergy (FA, n = 136), and allergic rhinitis (AR, n = 187). In a subset with shotgun metagenomic and metabolomic profiling (n = 589), we discover that impaired 1-year microbiota maturation may be universal to pediatric allergies (AD p = 0.000014; As p = 0.0073; FA p = 0.00083; and AR p = 0.0021). Extending this, we find a core set of functional and metabolic imbalances characterized by compromised mucous integrity, elevated oxida- tive activity, decreased secondary fermentation, and elevated trace amines, to be a significant mediator between microbiota maturation at age 1 year and allergic diagnoses at age 5 years (βindirect = −2.28; p = 0.0020). Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease.Link to publication (OA): https://www.nature.com/articles/s41467-023-40336-4
Distinctive signatures of pathogenic and antibiotic resistant potentials in the hadal microbiome
Authors: Huang Xinyu 
Published: September 2024

Background: Hadal zone of the deep-sea trenches accommodates microbial life under extreme energy limitations and environmental conditions, such as low temperature, high pressure, and low organic matter down to 11,000 meters below sea level. However, microbial pathogenicity, resistance, and adaptation therein remain unknown, especially identifying the genetic mobility of resistance and pathogenicity in unculturable trench bacteria is a great challenge. This study aims to depict the landscape of virulome, antibiotic resistome and mobilome of the hadal zone microbiota of the Mariana Trench.Method: The landscape of virulence and antibiotic resistance genes was depicted based on high-throughput metagenomic sequencing analysis using both sequence-based and domain-based annotation methods. The mobility and spread potentials of ARGs and virulence genes via horizontal gene transfer (HGT) were examined by checking their co-occurrence with MGEs.Results and Discussion: i) the Challenger Deep bottom (10,898-m) sediment harbored prosperous microbiota with contrasting signatures of virulence factors and antibiotic resistance (Fig. 1b and 2b), compared with the other Marian Trench sediment; ii) both the abundance and richness of ARGs greatly differed across sediment sites in the following increasing trend: SM10898 - SM6038 - SP5856 (Fig. 2a). Surprisingly, the bottom site of the Challenger Deep was found to still harbor 20 subtypes of known ARGs. Both the abundance (1.08 to 1.12×10-1 GP16S each) and diversity (127 to 153 subtypes) of the hadal seawater ARGs (Fig. 2b) were surprisingly high in the hadal seawater of the Mariana trench. The abundance of ARGs in seawater is higher than that in sediments by up to two orders of magnitude, deterministic natural processes drivers the resistome differences between hadal sediment and seawater including habitat (environmental) filtering and biotic interactions (e.g., competition). iii) HGT mediated by phage and integrase as the major mechanism for the evolution of Mariana Trench sediment bacteria (Fig. 3a); iv) substantial co-selection of virulence genes and ARGs in taxonomically diverse bacteria in the hadal sediment, especially for the Challenger Deep bottom where mobilized ARGs and virulence genes are favorably enriched in largely unexplored bacteria (Fig. 4).
Critical Assessment of Metagenome Interpretation - the second round of challenges
Authors: McHardy Alice 
Published: September 2024

Evaluating metagenomic software is key for optimizing metagenome interpretation and focus of the community-driven initiative for the Critical Assessment of Metagenome Interpretation (CAMI). In its second challenge, CAMI engaged the community to assess their methods on realistic and complex metagenomic datasets with long and short reads, created from ∼1,700 novel and known microbial genomes, as well as ∼600 novel plasmids and viruses. Altogether 5,002 results by 76 program versions were analyzed, representing a 22x increase in results.Substantial improvements were seen in metagenome assembly, some due to using long-read data. The presence of related strains still was challenging for assembly and genome binning, as was assembly quality for the latter. Taxon profilers demonstrated a marked maturation, with taxon profilers and binners excelling at higher bacterial taxonomic ranks, but underperforming for viruses and archaea. Assessment of clinical pathogen detection techniques revealed a need to improve reproducibility. Analysis of program runtimes and memory usage identified highly efficient programs, including some top performers with other metrics. The CAMI II results identify current challenges, but also guide researchers in selecting methods for specific analyses.
Establishment of a non-Westernized gut microbiota in men who have sex with men is associated with sexual practices
Authors: Huang Kun D. 
Published: September 2024

The human gut microbiota is influenced by various factors, including health status and environmental conditions, yet considerable inter-individual differences remain unexplained. Previous studies identified that the gut microbiota of men who have sex with men (MSM) is distinct from that of non-MSM. Here, we reveal through species-level microbiota analysis using shotgun metagenomics that the gut microbiota of many MSM with Western origin resembles gut microbial communities of non-Westernized populations. Specifically, MSM gut microbiomes are frequently dominated by members of the Prevotellaceae family, including co-colonization of species from the Segatella copri complex and unknown Prevotellaceae members. Questionnaire-based analysis exploring inter-individual differences in MSM links specific sexual practices to microbiota composition. Moreover, machine learning identifies microbial features associated with sexual activities in MSM. Together, this study shows associations of sexual activities with gut microbiome alterations in MSM, which may have a large impact on population-based microbiota studies.Link to publication: https://www.sciencedirect.com/science/article/pii/S2666379124000491
Software testing in microbial bioinformatics: a call to action
Authors: Mendes Inês 
Published: September 2024

Computational algorithms have become an essential component of microbiome research, with great efforts by the scientific community to raise standards on the development and distribution of code. Despite these efforts, sustainability and reproducibility are major issues since continued validation through software testing is still not a widely adopted practice. In the field of microbial bioinformatics, good software engineering practices are not yet widely adopted. Many microbial bioinformaticians start out as (micro)biologists and subsequently learn how to code. Without abundant formal training, a lot of education about good software engineering practices comes down to an exchange of information within the microbial bioinformatics community. Here, we report seven recommendations that help researchers implement software testing in microbial bioinformatics. These recommendations are: Establish software needs and testing goals; Use appropriate input test files; Use an easy-to-follow language format to implement testing; Try to automate testing; Test across multiple computational setups; and Encourage others to test your software. We propose collaborative software testing as an opportunity to continuously engage software users, developers, and students to unify scientific work across domains. As automated software testing remains underused in scientific software, our set of recommendations not only ensures appropriate effort can be invested into producing high quality and robust software but also increases engagement in its sustainability. We have developed these recommendations based on our experience from a collaborative hackathon organised prior to the American Society for Microbiology Next Generation Sequencing (ASM NGS) 2020 conference. We also present a repository hosting examples and guidelines for testing, available from https://github.com/microbinfie-hackathon2020/CSIS.Link to OA paper: https://www.microbiologyresearch.org/content/journal/mgen/10.1099/mgen.0.000790
Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome
Authors: Kindschuh William F. 
Published: September 2024

Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet its prevention and early risk stratification are limited. Previous investigations have suggested that vaginal microbes and metabolites may be implicated in sPTB. Here we performed untargeted metabolomics on 232 second-trimester vaginal samples, 80 from pregnancies ending preterm. We find multiple associations between vaginal metabolites and subsequent preterm birth, and propose that several of these metabolites, including diethanolamine and ethyl glucoside, are exogenous. We observe associations between the metabolome and microbiome profiles previously obtained using 16S ribosomal RNA amplicon sequencing, including correlations between bacteria considered suboptimal, such as Gardnerella vaginalis, and metabolites enriched in term pregnancies, such as tyramine. We investigate these associations using metabolic models. We use machine learning models to predict sPTB risk from metabolite levels, weeks to months before birth, with good accuracy (area under receiver operating characteristic curve of 0.78). These models, which we validate using two external cohorts, are more accurate than microbiome-based and maternal covariates-based models (area under receiver operating characteristic curve of 0.55–0.59). Our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.Link to paper: https://www.nature.com/articles/s41564-022-01293-8
Processed foods drive intestinal barrier permeability and microvascular diseases
Authors: Snelson Matthew 
Published: September 2024

Intake of processed foods has increased markedly over the past decades, coinciding with increased microvascular diseases such as chronic kidney disease (CKD) and diabetes. Here, we show in rodent models that long-term consumption of a processed diet drives intestinal barrier permeability and an increased risk of CKD. Inhibition of the advanced glycation pathway, which generates Maillard reaction products within foods upon thermal processing, reversed kidney injury. Consequently, a processed diet leads to innate immune complement activation and local kidney inflammation and injury via the potent proinflammatory effector molecule complement 5a (C5a). In a mouse model of diabetes, a high resistant starch fiber diet maintained gut barrier integrity and decreased severity of kidney injury via suppression of complement. These results demonstrate mechanisms by which processed foods cause inflammation that leads to chronic disease.Link to OA paper: https://www.science.org/doi/10.1126/sciadv.abe4841
Effective binning of metagenomic contigs using contrastive multi-view representation learning
Authors: Wang Ziye 
Published: September 2024

Contig binning plays a crucial role in metagenomic data analysis by grouping contigs from the same or closely related genomes. However, existing binning methods face challenges in practical applications due to the diversity of data types and the difficulties in efficiently integrating heterogeneous information. Here, we introduce COMEBin, a binning method based on contrastive multi-view representation learning. COMEBin utilizes data augmentation to generate multiple fragments (views) of each contig and obtains high-quality embeddings of heterogeneous features (sequence coverage and k-mer distribution) through contrastive learning. Experimental results on multiple simulated and real datasets demonstrate that COMEBin outperforms state-of-the-art binning methods, particularly in recovering near-complete genomes from real environmental samples. COMEBin outperforms other binning methods remarkably when integrated into metagenomic analysis pipelines, including the recovery of potentially pathogenic antibiotic-resistant bacteria (PARB) and moderate or higher quality bins containing potential biosynthetic gene clusters (BGCs).Link to OA paper: https://www.nature.com/articles/s41467-023-44290-z
Wastewater sequencing reveals community and variant dynamics of the collective human virome
Authors: Tisza Mike 
Published: September 2024

Wastewater is a discarded human by-product, but its analysis may help us understand the health of populations. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels while bypassing the difficulties and pit falls of individual testing. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. Here, we conduct a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Critical to detection is the use of a viral probe capture set targeting thousands of viral species or variants. Over 450 distinct pathogenic viruses from 28 viral families are observed, most of which have never been detected in such samples. Sequencing reads of established pathogens and emerging viruses correlate to clinical data sets of SARS-CoV-2, influenza virus, and monkeypox viruses, outlining the public health utility of this approach. Viral communities are tightly organized by space and time. Finally, the most abundant human viruses yield sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health.Link to OA paper: https://www.nature.com/articles/s41467-023-42064-1
Cas9-Assisted Biological Containment of a Genetically Engineered Human Commensal Bacterium and Genetic Elements
Authors: Hayashi Naoki 
Published: September 2024

Sophisticated gene circuits built by synthetic biology can enable bacteria to sense their environment and respond predictably. Engineered biosensing bacteria outfitted with such circuits can potentially probe the human gut microbiome to prevent, diagnose, or treat disease. To provide robust biocontainment for engineered bacteria, we devised a Cas9-assisted auxotrophic biocontainment system combining thymidine auxotrophy, an Engineered Riboregulator (ER) for controlled gene expression, and a CRISPR Device (CD). The CD prevents the engineered bacteria from acquiring thyA via horizontal gene transfer, which would disrupt the biocontainment system, and inhibits the spread of genetic elements by killing bacteria harboring the gene cassette. This system tunably controlled gene expression in the human gut commensal bacterium Bacteroides thetaiotaomicron, prevented escape from thymidine auxotrophy, and blocked transgene dissemination. These capabilities were validated in vitro and in vivo. This biocontainment system exemplifies a powerful strategy for bringing genetically engineered microorganisms safely into biomedicine.Link to OA paper: https://www.nature.com/articles/s41467-024-45893-w