Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

Nature Medicine, Год журнала: 2022, Номер 28(2), С. 315 - 324

Опубликована: Фев. 1, 2022

Язык: Английский

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Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions

Cell, Год журнала: 2022, Номер 185(20), С. 3789 - 3806.e17

Опубликована: Сен. 1, 2022

Cancer-microbe associations have been explored for centuries, but cancer-associated fungi rarely examined. Here, we comprehensively characterize the cancer mycobiome within 17,401 patient tissue, blood, and plasma samples across 35 types in four independent cohorts. We report fungal DNA cells at low abundances many major human cancers, with differences community compositions that differ among types, even when accounting technical background. Fungal histological staining of tissue microarrays supported intratumoral presence frequent spatial association macrophages. Comparing communities matched bacteriomes immunomes revealed co-occurring bi-domain ecologies, often permissive, rather than competitive, microenvironments distinct immune responses. Clinically focused assessments suggested prognostic diagnostic capacities mycobiomes, stage I synergistic predictive performance bacteriomes.

Язык: Английский

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Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma

Nature Medicine, Год журнала: 2022, Номер 28(3), С. 535 - 544

Опубликована: Фев. 28, 2022

Abstract The composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on specific characteristics linked benefits ICIs. We performed shotgun metagenomic sequencing stool samples collected before ICI initiation from five observational cohorts recruiting ICI-naive patients advanced cutaneous melanoma ( n = 165). Integrating dataset 147 previously published studies, we found that a relevant, cohort-dependent, association response A machine learning analysis confirmed link between and overall rates (ORRs) progression-free survival (PFS) ICIs also revealed reproducibility microbiome-based signatures across cohorts. Accordingly, panel species, including Bifidobacterium pseudocatenulatum , Roseburia spp. Akkermansia muciniphila responders was identified, no single species could be regarded as fully consistent biomarker studies. Overall, role human in appears more complex than thought, extending beyond differing microbial simply present or absent nonresponders. Future studies should adopt larger sample sizes take into account interplay factors over treatment course.

Язык: Английский

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Analysis of microbial compositions: a review of normalization and differential abundance analysis

npj Biofilms and Microbiomes, Год журнала: 2020, Номер 6(1)

Опубликована: Дек. 2, 2020

Abstract Increasingly, researchers are discovering associations between microbiome and a wide range of human diseases such as obesity, inflammatory bowel diseases, HIV, so on. The first step towards association studies is the characterization composition under different conditions. Determination differentially abundant microbes two or more environments, known differential abundance (DA) analysis, challenging an important problem that has received considerable interest during past decade. It well documented in literature observed data (OTU/SV table) relative abundances with excess zeros. Since sum to constant, these necessarily compositional. In this article we review some recent methods for DA analysis describe their strengths weaknesses.

Язык: Английский

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scCODA is a Bayesian model for compositional single-cell data analysis

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Ноя. 25, 2021

Compositional changes of cell types are main drivers biological processes. Their detection through single-cell experiments is difficult due to the compositionality data and low sample sizes. We introduce scCODA ( https://github.com/theislab/scCODA ), a Bayesian model addressing these issues enabling study complex type effects in disease, other stimuli. demonstrated excellent performance, while reliably controlling for false discoveries, identified experimentally verified that were missed original analyses.

Язык: Английский

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Best practices in metabarcoding of fungi: From experimental design to results

Molecular Ecology, Год журнала: 2022, Номер 31(10), С. 2769 - 2795

Опубликована: Апрель 8, 2022

The development of high-throughput sequencing (HTS) technologies has greatly improved our capacity to identify fungi and unveil their ecological roles across a variety ecosystems. Here we provide an overview current best practices in metabarcoding analysis fungal communities, from experimental design through molecular computational analyses. By reanalysing published data sets, demonstrate that operational taxonomic units (OTUs) outperform amplified sequence variants (ASVs) recovering diversity, finding is particularly evident for long markers. Additionally, the full-length ITS region allows more accurate placement other eukaryotes compared ITS2 subregion. Finally, show specific methods compositional analyses reliable estimates shifts community structure. We conclude are especially promising integrating into full microbiome broader ecosystem functioning context, recovery novel lineages ancient organisms as well barcoding old specimens including type material.

Язык: Английский

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Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Ноя. 15, 2022

Abstract Parkinson’s disease (PD) may start in the gut and spread to brain. To investigate role of microbiome, we conducted a large-scale study, at high taxonomic resolution, using uniform standardized methods from end. We enrolled 490 PD 234 control individuals, deep shotgun sequencing fecal DNA, followed by metagenome-wide association studies requiring significance two (ANCOM-BC MaAsLin2) declare association, network analysis identify polymicrobial clusters, functional profiling. Here show that over 30% species, genes pathways tested have altered abundances PD, depicting widespread dysbiosis. PD-associated species form clusters grow or shrink together, some compete. microbiome is permissive, evidenced overabundance pathogens immunogenic components, dysregulated neuroactive signaling, preponderance molecules induce alpha-synuclein pathology, over-production toxicants; with reduction anti-inflammatory neuroprotective factors limiting capacity recover. validate, human findings were observed experimental models; reconcile resolve literature; provide broad foundation wealth concrete testable hypotheses discern PD.

Язык: Английский

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LinDA: linear models for differential abundance analysis of microbiome compositional data

Genome biology, Год журнала: 2022, Номер 23(1)

Опубликована: Апрель 14, 2022

Abstract Differential abundance analysis is at the core of statistical microbiome data. The compositional nature sequencing data makes false positive control challenging. Here, we show that effects can be addressed by a simple, yet highly flexible and scalable, approach. proposed method, LinDA, only requires fitting linear regression models on centered log-ratio transformed data, correcting bias due to effects. We LinDA enjoys asymptotic FDR extended mixed-effect for correlated Using simulations real examples, demonstrate effectiveness LinDA.

Язык: Английский

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MicrobiotaProcess: A comprehensive R package for deep mining microbiome

The Innovation, Год журнала: 2023, Номер 4(2), С. 100388 - 100388

Опубликована: Фев. 2, 2023

The data output from microbiome research is growing at an accelerating rate, yet mining the quickly and efficiently remains difficult. There still a lack of effective structure to represent manage data, as well flexible composable analysis methods. In response these two issues, we designed developed

Язык: Английский

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ggpicrust2: an R package for PICRUSt2 predicted functional profile analysis and visualization

Bioinformatics, Год журнала: 2023, Номер 39(8)

Опубликована: Авг. 1, 2023

Microbiome research is now moving beyond the compositional analysis of microbial taxa in a sample. Increasing evidence from large human microbiome studies suggests that functional consequences changes intestinal may provide more power for studying their impact on inflammation and immune responses. Although 16S rRNA one most popular cost-effective method to profile compositions, marker-gene sequencing cannot direct information about genes are present genomes community members. Bioinformatic tools have been developed predict function with gene data. Among them, PICRUSt2 has become prediction tools, which generates community-wide pathway abundances. However, no state-of-art inference available test differences abundances between comparison groups. We ggpicrust2, an R package, do extensive differential abundance(DA) analyses publishable visualization highlight signals.

Язык: Английский

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