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Cobalamin (B12), an essential nutrient and growth cofactor for many living organisms on Earth, can be fully synthesized only by selected prokaryotes in nature. Therefore, microbial communities related to B12 biosynthesis could serve as an example subsystem to disentangle the underlying ecological mechanisms balancing the function and taxonomic make-up of complex functional assemblages. By anchoring microbial traits potentially involved in B12 biosynthesis, we depict the biogeographic patterns of B12 biosynthesis genes and the taxa harboring them in the global ocean, despite the limitations of detecting de novo B12 synthesizers via metagenomes alone. Both the taxonomic and functional composition of B12 biosynthesis genes were strongly shaped by depth, differentiating the epipelagic zones from the mesopelagic layers. Functional genes related to B12 biosynthesis were relatively stably distributed across different oceans, but the taxa harboring them varied considerably, showing clear functional redundancy among microbial systems. Microbial taxa carrying B12 biosynthesis genes in the surface water were influenced by environmental factors such as temperature, oxygen, and nitrate. However, the composition of functional genes was only weakly associated with these environmental factors. Null model analyses demonstrated that determinism governed the variations in B12 biosynthesis genes, whereas a higher degree of stochasticity was associated with taxonomic variations. Significant associations were observed between the chlorophyll a concentration and B12 biosynthesis, confirming its importance in primary production in the global ocean. The results of this study reveal an essential ecological mechanism governing the assembly of microbes in nature: the environment selects for function rather than taxonomy; functional redundancy underlies stochastic community assembly.

Cobalamin (vitamin B12; VB12) is an indispensable nutrient for all living entities in the Earth's biosphere and plays a vital role in both natural and host environments. Currently in the metagenomic era, gene families of interest are extracted and analyzed based on functional profiles by searching shotgun metagenomes against public databases. However, critical issues exist in applying public databases for specific processes such as VB12 biosynthesis pathways. We developed a curated functional gene database termed VB12Path for accurate metagenomic profiling of VB12 biosynthesis gene families of microbial communities in complex environments. VB12Path contains a total of 60 VB12 synthesis gene families, 287,731 sequences, and 21,154 homology groups, and it aims to provide accurate functional and taxonomic profiles of VB12 synthesis pathways for shotgun metagenomes and minimize false-positive assignments. VB12Path was applied to characterize cobalamin biosynthesis gene families in human intestines and marine environments. The results demonstrated that ocean and human intestine had dramatically different VB12 synthesis processes and that gene families belonging to salvage and remodeling pathway dominated human intestine but were lowest in the ocean ecosystem. VB12Path is expected to be a useful tool to study cobalamin biosynthesis processes via shotgun metagenome sequencing in both environmental and human microbiome research. IMPORTANCE Vitamin B12 (VB12) is an indispensable nutrient for all living entities in the world but can only be synthesized by a small subset of prokaryotes. Therefore, this small subset of prokaryotes controls ecosystem stability and host health to some extent. However, critical accuracy and comprehensiveness issues exist in applying public databases to profile VB12 synthetic gene families and taxonomic groups in complex metagenomes. In this study, we developed a curated functional gene database termed VB12Path for accurate metagenomic profiling of VB12 communities in complex environments. VB12Path is expected to serve as a valuable tool to uncover the hidden microbial communities producing this precious nutrient on Earth.

High-throughput profiling of microbial functional traits involved in various biogeochemical cycling pathways using shotgun metagenomic sequencing has been routinely applied in microbial ecology and environmental science. Multiple bioinformatics data processing approaches are available, including assembly-based (single-sample assembly and multi-sample assembly) and read-based (merged reads and raw data). However, it remains not clear how these different approaches may differ in data analyses and affect result interpretation. In this study, using two typical shotgun metagenome datasets recovered from geographically distant coastal sediments, the performance of different data processing approaches was comparatively investigated from both technical and biological/ecological perspectives. Microbially mediated biogeochemical cycling pathways, including nitrogen cycling, sulfur cycling and B12 biosynthesis, were analyzed. As a result, multi-sample assembly provided the most amount of usable information for targeted functional traits, at a high cost of computational resources and running time. Single-sample assembly and read-based analysis were comparable in obtaining usable information, but the former was much more time- and resource-consuming. Critically, different approaches introduced much stronger variations in microbial profiles than biological differences. However, community-level differences between the two sampling sites could be consistently observed despite the approaches being used. In choosing an appropriate approach, researchers shall balance the trade-offs between multiple factors, including the scientific question, the amount of usable information, computational resources and time cost. This study is expected to provide valuable technical insights and guidelines for the various approaches used for metagenomic data analysis. [ABSTRACT FROM AUTHOR]

In mammals, histone 3 lysine 4 methylation (H3K4me) is mediated by six different lysine methyltransferases. Among these enzymes, SETD1B (SET domain containing 1b) has been linked to syndromic intellectual disability in human subjects, but its role in the mammalian postnatal brain has not been studied yet. Here, we employ mice deficient for Setd1b in excitatory neurons of the postnatal forebrain, and combine neuron‐specific ChIP‐seq and RNA‐seq approaches to elucidate its role in neuronal gene expression. We observe that Setd1b controls the expression of a set of genes with a broad H3K4me3 peak at their promoters, enriched for neuron‐specific genes linked to learning and memory function. Comparative analyses in mice with conditional deletion of Kmt2a and Kmt2b histone methyltransferases show that SETD1B plays a more pronounced and potent role in regulating such genes. Moreover, postnatal loss of Setd1b leads to severe learning impairment, suggesting that SETD1B‐dependent regulation of H3K4me levels in postnatal neurons is critical for cognitive function. Synopsis: Mammalian histone H3K4 methyltransferases are linked to neurodevelopmental intellectual disability disorders. Conditional postnatal deletion studies reveal a specific role of Setd1b‐controlled gene expression programs, suggesting a potential target for treating cognitive impairment in patients. Postnatal deletion of the H3K4 methyltransferase Setd1b from neurons of the mouse forebrain leads to severe learning impairment.SETD1B in postnatal neurons controls the expression of neuron‐specific genes with a broad H3K4me3 peak, and with roles in learning and memory.Neuronal gene‐expression programs controlled by SETD1B differ substantially from those controlled by the H3K4 methyltransferases KMT2A and KMT2B.Postnatal loss of Setd1b leads to severe learning impairment in mice. [ABSTRACT FROM AUTHOR]

A novel vessel context-based voting is proposed for automatic liver vasculature segmentation in CT images. It is able to conduct full vessel segmentation and recognition of multiple vasculatures effectively. The vessel context describes context information of a voxel related to vessel properties, such as intensity, saliency, direction, and connectivity. Voxels are grouped to liver vasculatures hierarchically based on vessel context. They are first grouped locally into vessel branches with the advantage of a vessel junction measurement and then grouped globally into vasculatures, which is implemented using a multiple feature point voting mechanism. The proposed method has been evaluated on ten clinical CT datasets. Segmentation of third-order vessel trees from CT images (0.76 × 0.76 × 2.0 mm) of the portal venous phase takes less than 3 min on a PC with 2.0 GHz dual core processor and the average segmentation accuracy is up to 98%. [ABSTRACT FROM PUBLISHER]

Cobalamin (B 12 ), an essential nutrient and growth cofactor for many living organisms on Earth, can be fully synthesized only by selected prokaryotes in nature. Therefore, microbial communities related to B 12 biosynthesis could serve as an example subsystem to disentangle the underlying ecological mechanisms balancing the function and taxonomic make-up of complex functional assemblages. By anchoring microbial traits potentially involved in B 12 biosynthesis, we depict the biogeographic patterns of B 12 biosynthesis genes and the taxa harboring them in the global ocean, despite the limitations of detecting de novo B 12 synthesizers via metagenomes alone. Both the taxonomic and functional composition of B 12 biosynthesis genes were strongly shaped by depth, differentiating the epipelagic zones from the mesopelagic layers. Functional genes related to B 12 biosynthesis were relatively stably distributed across different oceans, but the taxa harboring them varied considerably, showing clear functional redundancy among microbial systems. Microbial taxa carrying B 12 biosynthesis genes in the surface water were influenced by environmental factors such as temperature, oxygen, and nitrate. However, the composition of functional genes was only weakly associated with these environmental factors. Null model analyses demonstrated that determinism governed the variations in B 12 biosynthesis genes, whereas a higher degree of stochasticity was associated with taxonomic variations. Significant associations were observed between the chlorophyll a concentration and B 12 biosynthesis, confirming its importance in primary production in the global ocean. The results of this study reveal an essential ecological mechanism governing the assembly of microbes in nature: the environment selects for function rather than taxonomy; functional redundancy underlies stochastic community assembly., Competing Interests: The authors declare no conflict of interests., (© 2023 The Authors. mLife published by John Wiley & Sons Australia, Ltd on behalf of Institute of Microbiology, Chinese Academy of Sciences.)

We propose a new variant of the Mumford-Shah model for simultaneous bias correction and segmentation of images with intensity inhomogeneity. First, based on the model of images with intensity inhomogeneity, we introduce an L0 gradient regularizer to model the true intensity and a smooth regularizer to model the bias field. In addition, we derive a new data fidelity using the local intensity properties to allow the bias field to be influenced by its neighborhood. Second, we use a two-stage segmentation method, where the fast alternating direction method is implemented in the first stage for the recovery of true intensity and bias field and a simple thresholding is used in the second stage for segmentation. Different from most of the existing methods for simultaneous bias correction and segmentation, we estimate the bias field and true intensity without fixing either the number of the regions or their values in advance. Our method has been validated on medical images of various modalities with intensity inhomogeneity. Compared with the state-of-art approaches and the well-known brain software tools, our model is fast, accurate, and robust with initializations.