Small amounts of misassembly can have disproportionate effects on pangenome-based metagenomic analyses.

Unlabelled: Individual genes from microbiomes can drive host-level phenotypes. To help identify such candidate genes, several recent tools estimate microbial gene copy numbers directly from metagenomes. These tools rely on alignments to pangenomes, which in turn are derived from the set of all individual genomes from one species.

Adaptive adjustment of significance thresholds produces large gains in microbial gene annotations and metabolic insights.

Gene function annotations enable microbial ecologists to make inferences about metabolic potential from genomes and metagenomes. However, even tools that use the same database and general approach can differ markedly in the annotations they recover. We compare three popular methods for identifying KEGG Orthologs, applying them to genomes drawn from a range of bacterial families that occupy different host-associated and free-living biomes.

Framework for exploring the sensory repertoire of the human gut microbiota.

Bacteria sense changes in their environment and transduce signals to adjust their cellular functions accordingly. For this purpose, bacteria employ various sensors feeding into multiple signal transduction pathways. Signal recognition by bacterial sensors is studied mainly in a few model organisms, but advances in genome sequencing and analysis offer new ways of exploring the sensory repertoire of many understudied organisms.

Four-part harmony between diet, drugs, microbes, and host.

In this issue of Cell Host & Microbe, Zeng et al. show that a specific gut microbe causes diet-dependent attenuation of acetaminophen toxicity in mice. This link between gut microbes and toxicity is mechanistically detailed, yet intriguingly indirect, mediated by the transformation of ingested phytochemicals as opposed to the drug itself.

Host and gut bacteria share metabolic pathways for anti-cancer drug metabolism.

Pharmaceuticals have extensive reciprocal interactions with the microbiome, but whether bacterial drug sensitivity and metabolism is driven by pathways conserved in host cells remains unclear. Here we show that anti-cancer fluoropyrimidine drugs inhibit the growth of gut bacterial strains from 6 phyla. In both Escherichia coli and mammalian cells, fluoropyrimidines disrupt pyrimidine metabolism.

phylogenize: correcting for phylogeny reveals genes associated with microbial distributions.

Summary: Phylogenetic comparative methods are powerful but presently under-utilized ways to identify microbial genes underlying differences in community composition. These methods help to identify functionally important genes because they test for associations beyond those expected when related microbes occupy similar environments. We present phylogenize, a pipeline with web, QIIME 2 and R interfaces that allows researchers to perform phylogenetic regression on 16S amplicon and shotgun sequencing data and to visualize results.

Minor Isozymes Tailor Yeast Metabolism to Carbon Availability.

Isozymes are enzymes that differ in sequence but catalyze the same chemical reactions. Despite their apparent redundancy, isozymes are often retained over evolutionary time, suggesting that they contribute to fitness. We developed an unsupervised computational method for identifying environmental conditions under which isozymes are likely to make fitness contributions.

Phylogeny-corrected identification of microbial gene families relevant to human gut colonization.

The mechanisms by which different microbes colonize the healthy human gut versus other body sites, the gut in disease states, or other environments remain largely unknown. Identifying microbial genes influencing fitness in the gut could lead to new ways to engineer probiotics or disrupt pathogenesis. We approach this problem by measuring the statistical association between a species having a gene and the probability that the species is present in the gut microbiome.

Proteobacteria explain significant functional variability in the human gut microbiome.

Background: While human gut microbiomes vary significantly in taxonomic composition, biological pathway abundance is surprisingly invariable across hosts. We hypothesized that healthy microbiomes appear functionally redundant due to factors that obscure differences in gene abundance between individuals.

Results: To account for these biases, we developed a powerful test of gene variability called CCoDA, which is applicable to shotgun metagenomes from any environment and can integrate data from multiple studies.

Automated and Accurate Estimation of Gene Family Abundance from Shotgun Metagenomes.

Shotgun metagenomic DNA sequencing is a widely applicable tool for characterizing the functions that are encoded by microbial communities. Several bioinformatic tools can be used to functionally annotate metagenomes, allowing researchers to draw inferences about the functional potential of the community and to identify putative functional biomarkers. However, little is known about how decisions made during annotation affect the reliability of the results.

A new system for comparative functional genomics of Saccharomyces yeasts.

Whole-genome sequencing, particularly in fungi, has progressed at a tremendous rate. More difficult, however, is experimental testing of the inferences about gene function that can be drawn from comparative sequence analysis alone. We present a genome-wide functional characterization of a sequenced but experimentally understudied budding yeast, Saccharomyces bayanus var.

Phylogenetic portrait of the Saccharomyces cerevisiae functional genome.

The genome of budding yeast (Saccharomyces cerevisiae) contains approximately 5800 protein-encoding genes, the majority of which are associated with some known biological function. Yet the extent of amino acid sequence conservation of these genes over all phyla has only been partially examined. Here we provide a more comprehensive overview and visualization of the conservation of yeast genes and a means for browsing and exploring the data in detail, down to the individual yeast gene, at http://yeast-phylogroups.

Yeast cells can access distinct quiescent states.

We conducted a phenotypic, transcriptional, metabolic, and genetic analysis of quiescence in yeast induced by starvation of prototrophic cells for one of three essential nutrients (glucose, nitrogen, or phosphate) and compared those results with those obtained with cells growing slowly due to nutrient limitation. These studies address two related questions: (1) Is quiescence a state distinct from any attained during mitotic growth, and (2) does the nature of quiescence differ depending on the means by which it is induced? We found that either limitation or starvation for any of the three nutrients elicits all of the physiological properties associated with quiescence, such as enhanced cell wall integrity and resistance to heat shock and oxidative stress. Moreover, the starvations result in a common transcriptional program, which is in large part a direct extrapolation of the changes that occur during slow growth.

Growth-limiting intracellular metabolites in yeast growing under diverse nutrient limitations.

Microbes tailor their growth rate to nutrient availability. Here, we measured, using liquid chromatography-mass spectrometry, >100 intracellular metabolites in steady-state cultures of Saccharomyces cerevisiae growing at five different rates and in each of five different limiting nutrients. In contrast to gene transcripts, where approximately 25% correlated with growth rate irrespective of the nature of the limiting nutrient, metabolite concentrations were highly sensitive to the limiting nutrient's identity.

Coordinated concentration changes of transcripts and metabolites in Saccharomyces cerevisiae.

Metabolite concentrations can regulate gene expression, which can in turn regulate metabolic activity. The extent to which functionally related transcripts and metabolites show similar patterns of concentration changes, however, remains unestablished. We measure and analyze the metabolomic and transcriptional responses of Saccharomyces cerevisiae to carbon and nitrogen starvation.