Advances in metagenomic assembly have led to the discovery of genomes belonging to uncultured microorganisms. Metagenome-assembled genomes (MAGs) often suffer from fragmentation and chimerism. ...Recently, 20 complete MAGs (cMAGs) have been assembled from Oxford Nanopore long-read sequencing of 13 human fecal samples, but with low nucleotide accuracy. Here, we report 102 cMAGs obtained by Pacific Biosciences (PacBio) high-accuracy long-read (HiFi) metagenomic sequencing of five human fecal samples, whose initial circular contigs were selected for complete prokaryotic genomes using our bioinformatics workflow. Nucleotide accuracy of the final cMAGs was as high as that of Illumina sequencing. The cMAGs could exceed 6 Mbp and included complete genomes of diverse taxa, including entirely uncultured RF39 and TANB77 orders. Moreover, cMAGs revealed that regions hard to assemble by short-read sequencing comprised mostly genomic islands and rRNAs. HiFi metagenomic sequencing will facilitate cataloging accurate and complete genomes from complex microbial communities, including uncultured species.
Abstract
Transcription factors (TFs) are major trans-acting factors in transcriptional regulation. Therefore, elucidating TF-target interactions is a key step toward understanding the regulatory ...circuitry underlying complex traits such as human diseases. We previously published a reference TF-target interaction database for humans-TRRUST (Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining)-which was constructed using sentence-based text mining, followed by manual curation. Here, we present TRRUST v2 (www.grnpedia.org/trrust) with a significant improvement from the previous version, including a significantly increased size of the database consisting of 8444 regulatory interactions for 800 TFs in humans. More importantly, TRRUST v2 also contains a database for TF-target interactions in mice, including 6552 TF-target interactions for 828 mouse TFs. TRRUST v2 is also substantially more comprehensive and less biased than other TF-target interaction databases. We also improved the web interface, which now enables prioritization of key TFs for a physiological condition depicted by a set of user-input transcriptional responsive genes. With the significant expansion in the database size and inclusion of the new web tool for TF prioritization, we believe that TRRUST v2 will be a versatile database for the study of the transcriptional regulation involved in human diseases.
Inflammatory bowel disease (IBD) is an idiopathic inflammatory disorder characterized by chronic and relapsing manifestations. Several environmental factors are known as triggers for exacerbation of ...IBD. However, an association between exacerbation of IBD and ambient temperature is uncertain. This study aimed to estimate the risk of acute exacerbation of IBD due to ambient temperature. We performed a bidirectional case-crossover study using a nationwide claim data from South Korea. The external validation was conducted with a large prospective cohort in the United Kingdom. We confirmed significant associations between acute exacerbation of IBD and the short-term ambient temperature changes toward severe temperatures, in the cold weather (-19.4°C-4.3°C) (odd ratio OR = 1.13, 95% confidence interval CI: 1.13-1.14) and in the hot weather (21.3°C-33.5°C) (OR = 1.16, 95% CI: 1.15-1.17). However, the association was not significant in the moderate weather (4.3°C-21.3°C). The external validation suggested consistent results with additional elevation of acute exacerbation risk in the colder weather (-13.4°C to 2.6°C) (OR = 1.90, 95% CI: 1.62-2.22) and in the hotter weather (15.7°C-28.4°C) (OR = 1.41, 95% CI: 1.32-1.51). We observed and validated that the short-term ambient temperature changes were associated with acute exacerbation of IBD in the cold and hot weathers. Our findings provide evidence that temperature changes are associated with the acute exacerbation of IBD.
The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor‐associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune ...cells include hindering T‐cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non‐small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T‐cell activities leading to poor clinical outcomes. First, we verified PMN‐MDSCs, monocytic‐MDSCs (M‐MDSCs), and Treg cells increased according to the stages of NSCLC, and MDSCs effectively suppressed T‐cell activities and induced T‐cell exhaustion. The analysis of NSCLC patients treated with anti‐PD‐1 immunotherapy demonstrated that low PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells as an individual and all together were associated with longer progression free survival and overall survival, suggesting PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers.
Pre‐existing PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells can be used as predictive biomarkers in anti‐PD‐1 immunotherapy targeting NSCLC. Together with MDSCs, IL‐10 possibly released by suppressive immune cells also leads poor clinical outcomes. Therefore, combinatorial strategies targeting MDSCs or IL‐10 should be investigated to improve outcomes of immune checkpoint inhibitors.
The reconstruction of transcriptional regulatory networks (TRNs) is a long-standing challenge in human genetics. Numerous computational methods have been developed to infer regulatory interactions ...between human transcriptional factors (TFs) and target genes from high-throughput data, and their performance evaluation requires gold-standard interactions. Here we present a database of literature-curated human TF-target interactions, TRRUST (transcriptional regulatory relationships unravelled by sentence-based text-mining, http://www.grnpedia.org/trrust), which currently contains 8,015 interactions between 748 TF genes and 1,975 non-TF genes. A sentence-based text-mining approach was employed for efficient manual curation of regulatory interactions from approximately 20 million Medline abstracts. To the best of our knowledge, TRRUST is the largest publicly available database of literature-curated human TF-target interactions to date. TRRUST also has several useful features: i) information about the mode-of-regulation; ii) tests for target modularity of a query TF; iii) tests for TF cooperativity of a query target; iv) inferences about cooperating TFs of a query TF; and v) prioritizing associated pathways and diseases with a query TF. We observed high enrichment of TF-target pairs in TRRUST for top-scored interactions inferred from high-throughput data, which suggests that TRRUST provides a reliable benchmark for the computational reconstruction of human TRNs.
The massive proliferation of
Microcystis
threatens freshwater ecosystems and degrades water quality globally. Understanding the mechanisms that contribute to
Microcystis
growth is crucial for ...managing
Microcystis
blooms. The lifestyles of bacteria can be classified generally into two groups: particle-attached (PA; > 3 µm) and free-living (FL; 0.2–3.0 µm). However, little is known about the response of PA and FL bacteria to
Microcystis
blooms. Using 16S rRNA gene high-throughput sequencing, we investigated the stability, assembly process, and co-occurrence patterns of PA and FL bacterial communities during distinct bloom stages. PA bacteria were phylogenetically different from their FL counterparts.
Microcystis
blooms substantially influenced bacterial communities. The time decay relationship model revealed that
Microcystis
blooms might increase the stability of both PA and FL bacterial communities. A contrasting community assembly mechanism was observed between the PA and FL bacterial communities. Throughout
Microcystis
blooms, homogeneous selection was the major assembly process that impacted the PA bacterial community, whereas drift explained much of the turnover of the FL bacterial community. Both PA and FL bacterial communities could be separated into modules related to different phases of
Microcystis
blooms.
Microcystis
blooms altered the assembly process of PA and FL bacterial communities. PA bacterial community appeared to be more responsive to
Microcystis
blooms than FL bacteria. Decomposition of
Microcystis
blooms may enhance cooperation among bacteria. Our findings highlight the importance of studying bacterial lifestyles to understand their functions in regulating
Microcystis
blooms.
Key points
• Microcystis blooms alter the assembly process of PA and FL bacterial communities
• Microcystis blooms increase the stability of both PA and FL bacterial communities
• PA bacteria seem to be more responsive to Microcystis blooms than FL bacteria
Graphical Abstract
Lee, J.-C.; Koh, Y.-C., and Lee, D.-H., 2021. Strategic improvement plan to increase the usability of coastal base maps throughout Korea. In: Lee, J.L.; Suh, K.-S.; Lee, B.; Shin, S., and Lee, J. ...(eds.), Crisis and Integrated Management for Coastal and Marine Safety. Journal of Coastal Research, Special Issue No. 114, pp. 395–399. Coconut Creek (Florida), ISSN 0749–0208. The National Geographic Information Institute constructs and supplies coastal base maps containing spatial and geographic information. The main purpose is securing basic data for designing and developing coastal waters. However, there has been no continuous construction of information for all coastal waters in Korea; therefore, detailed and precise coastal water information for each coastal situation cannot be provided. This study introduces a continuous and unified coastal base map for all coastal waters in Korea. The introduced map can be employed to provide coastal water information with high utility, and widely used not only in coastal construction projects but also in various industries related to the spatial development of coastal waters.
Metagenome sampling bias for geographical location and lifestyle is partially responsible for the incomplete catalog of reference genomes of gut microbial species. Thus, genome assembly from ...currently under-represented populations may effectively expand the reference gut microbiome and improve taxonomic and functional profiling.
We assembled genomes using public whole-metagenomic shotgun sequencing (WMS) data for 110 and 645 fecal samples from India and Japan, respectively. In addition, we assembled genomes from newly generated WMS data for 90 fecal samples collected from Korea. Expecting genome assembly for low-abundance species may require a much deeper sequencing than that usually employed, so we performed ultra-deep WMS (> 30 Gbp or > 100 million read pairs) for the fecal samples from Korea. We consequently assembled 29,082 prokaryotic genomes from 845 fecal metagenomes for the three under-represented Asian countries and combined them with the Unified Human Gastrointestinal Genome (UHGG) to generate an expanded catalog, the Human Reference Gut Microbiome (HRGM).
HRGM contains 232,098 non-redundant genomes for 5414 representative prokaryotic species including 780 that are novel, > 103 million unique proteins, and > 274 million single-nucleotide variants. This is an over 10% increase from the UHGG. The new 780 species were enriched for the Bacteroidaceae family, including species associated with high-fiber and seaweed-rich diets. Single-nucleotide variant density was positively associated with the speciation rate of gut commensals. We found that ultra-deep sequencing facilitated the assembly of genomes for low-abundance taxa, and deep sequencing (e.g., > 20 million read pairs) may be needed for the profiling of low-abundance taxa. Importantly, the HRGM significantly improved the taxonomic and functional classification of sequencing reads from fecal samples. Finally, analysis of human self-antigen homologs on the HRGM species genomes suggested that bacterial taxa with high cross-reactivity potential may contribute more to the pathogenesis of gut microbiome-associated diseases than those with low cross-reactivity potential by promoting inflammatory condition.
By including gut metagenomes from previously under-represented Asian countries, Korea, India, and Japan, we developed a substantially expanded microbiome catalog, HRGM. Information of the microbial genomes and coding genes is publicly available ( www.mbiomenet.org/HRGM/ ). HRGM will facilitate the identification and functional analysis of disease-associated gut microbiota.
The skin tissue of the scalp is unique from other skin tissues because it coexists with hair, and many differences in microbial composition have been confirmed. In scalp tissues, hair loss occurs due ...to a combination of internal and external factors, and several studies are being conducted to counteract this. However, not many studies have addressed hair loss from the perspective of the microbiome. In this study, subjects with hair loss and those with normal scalps were set as experimental and control groups, respectively. In the experimental group, hair loss had progressed, and there was a large difference in microbiome composition compared to the group with normal scalps. In particular, differences in Accumulibacter, Staphylococcus, and Corynebacterium were found. From Staphylococcus epidermidis Cicaria, two active components were isolated as a result of repeated column chromatography. Spectroscopic data led to the determination of chemical structures for adenosine and biotin. Fractions were obtained, and ex vivo tests were conducted using hair follicles derived from human scalp tissue. When the microbiome adenosine-treated group was compared to the control group, hair follicle length was increased, and hair root diameter was maintained during the experimental periods. In addition, the Cicaria culture medium and the microbial adenosine- and biotin-treated groups maintained the anagen phase, reducing progression to the catagen phase in the hair growth cycle. In conclusion, it was confirmed that the Cicaria culture medium and the microbial adenosine and biotin derived from the culture were effective in inhibiting hair loss.
Allotransplantation, performed using an acellular dermal matrix (ADM), plays a significant role in the cultivation of constituted and damaged organs in clinical. Herein, we fabricated an innovative ...ADM for allografting derived from decellularized human skin by utilizing the supercritical fluid of carbon dioxide to eliminate immunogenic components. By using histological staining, the ADM product demonstrated the successful removal of cellular constituents without exerting any harmful influence on the extracellular matrix. The results from DNA electrophoresis also supported this phenomenon by showing the complete DNA removal in the product, accompanied by the absence of Major Histocompatibility Complex 1, which suggested the supercritical fluid is an effective method for cellular withdrawal. Moreover, the mechanical property of the ADM products, which showed similarity to that of native skin, displayed great compatibility for using our human‐derived ADM as an allograft in clinical treatment. Specifically, the cell viability demonstrated the remarkable biocompatibility of the product to human bio‐cellular environment which was noticeably higher than that of other products. Additionally, the significant increase in the level of growth factors such as vascular endothelial growth factor, urokinase‐type plasminogen activator receptor, granulocyte‐macrophage colony‐stimulating factor suggested the ability to stimulate cellular processes, proving the products to be innovative in the field of regeneration when applied to clinical in the future. This study provides a thoroughly extensive analysis of the new ADM products, enabling them to be applied in industrial and clinical treatment.
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