Motivation The growing number of microbial reference genomes enables the improvement of metagenomic profiling accuracy but also imposes greater requirements on the indexing efficiency, database size, and runtime of taxonomic profilers. Additionally, most profilers focus mainly on bacterial, archaeal, and fungal populations, while less attention is paid to viral communities. Results We present KMCP, a novel k-mer-based metagenomic profiling tool that utilizes genome coverage information by splitting the reference genomes into chunks and stores k-mers in a modified and optimized COBS index for fast alignment-free sequence searching. KMCP combines k-mer similarity and genome coverage information to reduce the false positive rate of k-mer-based taxonomic classification and profiling methods. Benchmarking results based on simulated and real data demonstrate that KMCP, despite a longer running time than all other methods, not only allows the accurate taxonomic profiling of prokaryotic and viral populations but also provides more confident pathogen detection in clinical samples of low depth. Availability The software is open-source under the MIT license and available at https://github.com/shenwei356/kmcp. Supplementary information Supplementary data are available at Bioinformatics online.
The classic carbon tetrachloride (CCl 4 )-induced liver injury model is widely used to study the pathogenesis of fibrosis and evaluate anti-fibrosis drugs. Here, we investigated the dynamic changes in the gut microbiota, bile acids (BAs) and the gut barrier over different fibrosis severities in a CCl 4 -based model. 16S rDNA sequencing demonstrated that the beneficial taxon Lactobacillus was always underrepresented, and pathogens including Escherichia_Shigella , Clostridium_sensu_stricto_1 , Colidextribacter , and Lachnospiraceae_UCG_010 were significantly overrepresented across liver fibrosis severities. Gut dysbiosis was more severe at the early stage of liver injury and advanced stage of fibrosis. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis revealed that with the progress of fibrosis, unconjugated BAs in faeces were significantly decreased and conjugated BAs in serum were significantly increased. The FXR-SHP signalling pathway in the liver and ileum was statistically repressed in the fibrosis groups. Determination of lipopolysaccharide (LPS) and fluorescein isothiocyanate (FITC)-dextran levels in plasma showed that the intestinal barrier remained relatively intact in the advanced fibrosis stage. The advances in knowledge of the gut-liver axis provided by this study yield new insights for application in research and drug evaluation.
A growing number of microbial reference genomes enable better metagenomic profiling accuracy yet put higher requirements on the indexing efficiency, database size, and runtime of taxonomic profilers. Besides, most profilers focused mainly on bacterial, archaeal, and fungal populations with less attention on viral communities. We present KMCP, a novel k-mer based metagenomic profiling tool that introduces genomic positions to k-mers by splitting the reference genomes into chunks. Benchmarking results on both simulated and real data demonstrate that KMCP not only allows for accurate taxonomic profiling of archaea, bacteria, and viral populations from metagenomic shotgun sequence data, but also provides confident pathogen detection for infectious clinical samples of low depth. KMCP is implemented in Go and is available as open-source software, under MIT, at https://github.com/shenwei356/kmcp.
Background Ganxianfang (GXF) formula as a traditional Chinese medicine (TCM) is used for liver fibrosis in clinical practice while its mechanism is unclear. The aim of this study is to explore the molecular mechanism of GXF against CCl4-induced liver fibrosis rats. Methods Detected the main compounds of GXF by UPLC-MS/MS. Evaluated the efficacy of GXF (1.58, 3.15, 4.73 g/kg/day) and Fuzheng Huayu (FZHY, positive control, 0.47 g/kg/day) through serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels and histopathological changes. Explored the underlying mechanisms by integrating our total liver RNA sequencing (RNA-seq) data with recent liver single-cell sequencing (scRNA-seq) studies. Verified potential pharmacodynamic substances of GXF by hepatic stellate cell (HSC)-T6 line. Results Main compounds were identified in GXF by UPLC-MS/MS, including baicalin, wogonoside and matrine etc. With GXF-high dose treatment, the elevation of ALT and AST induced by CCl4 were significantly reduced, and the protective effect of GXF-high dose treatment was better than FZHY. Liver histopathological changes were alleviated by GXF-high dose treatment, the ISHAK scoring showed the incidence of liver cirrhosis (F5/F6) decreased from 76.5 to 55.6%. The results of liver hydroxyproline content were consistent with the histopathological changes. RNA-seq analysis revealed the differential genes (DEGs) were mainly enriched in ECM-receptor interaction and chemokine signaling pathway. GXF effectively inhibited collagen deposition and significantly downregulated CCL2 to inhibit the recruitment of macrophages in liver tissue. Integrating scRNA-seq data revealed that GXF effectively inhibited the expansion of scar-associated Trem2+CD9+ macrophages subpopulation and PDGFRα+PDGFRβ+ scar-producing myofibroblasts in the damaged liver, and remodeled the fibrotic niche via regulation of ligand-receptor interactions including TGFβ/EGFR, PDGFB/PDGFRα, and TNFSF12/TNFRSF12a signaling. In vitro experiments demonstrated that baicalin, matrine and hesperidin in GXF inhibited the activation of hepatic stellate cells. Conclusions This study clarified the potential anti-fibrotic effects and molecular mechanism of GXF in CCl4-induced liver fibrosis rats, which deserves further promotion and application.
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