Exploring the functional composition of the human microbiome using a hand-curated microbial trait database

Even when microbial communities vary wildly in their taxonomic composition, their functional composition is often surprisingly stable. This suggests that a functional perspective could provide much deeper insight into the principles governing microbiome assembly. Much work to date analyzing the functional composition of microbial communities, however, relies heavily on inference from genomic features. Unfortunately, output from these methods can be hard to interpret and often suffers from relatively high error rates. We built and analyzed a domain-specific microbial trait database from known microbe-trait pairs recorded in the literature to better understand the functional composition of the human microbiome. Using a combination of phylogentically conscious machine learning tools and a network science approach, we were able to link particular traits to areas of the human body, discover traits that determine the range of body areas a microbe can inhabit, and uncover drivers of metabolic breadth. Domain-specific trait databases are an effective compromise between noisy methods to infer complex traits from genomic data and exhaustive, expensive attempts at database curation from the literature that do not focus on any one subset of taxa. They provide an accurate account of microbial traits and, by limiting the number of taxa considered, are feasible to build within a reasonable time-frame. We present a database specific for the human microbiome, in the hopes that this will prove useful for research into the functional composition of human-associated microbial communities.https://doi.org/10.1186/s12859-021-04216-

Altered Differentiation Potential of Gaucherâs Disease iPSC Neuronal Progenitors due to Wnt/β-Catenin Downregulation

Summary: Gaucherâs disease (GD) is an autosomal recessive disorder caused by mutations in the GBA1 gene, which encodes acid β-glucocerebrosidase (GCase). Severe GBA1 mutations cause neuropathology that manifests soon after birth, suggesting that GCase deficiency interferes with neuronal development. We found that neuronopathic GD induced pluripotent stem cell (iPSC)-derived neuronal progenitor cells (NPCs) exhibit developmental defects due to downregulation of canonical Wnt/β-catenin signaling and that GD iPSCsâ ability to differentiate to dopaminergic (DA) neurons was strikingly reduced due to early loss of DA progenitors. Incubation of the mutant cells with the Wnt activator CHIR99021 (CHIR) or with recombinant GCase restored Wnt/β-catenin signaling and rescued DA differentiation. We also found that GD NPCs exhibit lysosomal dysfunction, which may be involved in Wnt downregulation by mutant GCase. We conclude that neuronopathic mutations in GCase lead to neurodevelopmental abnormalities due to a critical requirement of this enzyme for canonical Wnt/β-catenin signaling at early stages of neurogenesis. : In this article, Feldman and colleagues describe a new mechanism linking severe GBA1 mutations to neurodevelopmental defects through Wnt/β-catenin downregulation. Using GD iPSCs as a model, the authors show that the ability of neuronopathic GD NPCs to differentiate to DA neurons is strikingly reduced due to early loss of DA progenitors and that lysosomal dysfunction may be directly involved in canonical Wnt downregulation. Keywords: Gaucherâs disease, GBA1, glucocerebrosidase, neuronal progenitors, dopaminergic development, iPSCs, Wnt/β-catenin, lysosomal storage disease, neurodegeneratio

Additional file 1 of Exploring the functional composition of the human microbiome using a hand-curated microbial trait database

Additional file 1. Trait Database

Additional file 1 of Exploring the functional composition of the human microbiome using a hand-curated microbial trait database

Additional file 1. Trait Database

Additional file 1 of Exploring the functional composition of the human microbiome using a hand-curated microbial trait database

Additional file 1. Trait Database