Viruses have caused much mortality and morbidity to humans and pose a serious threat to global public health. The virome with the potential of human infection is still far from complete. Novel viruses have been discovered at an unprecedented pace as the rapid development of viral metagenomics. However, there is still a lack of methodology for rapidly identifying novel viruses with the potential of human infection. This study built several machine learning models to discriminate human‐infecting viruses from other viruses based on the frequency of k‐mers in the viral genomic sequences. The k‐nearest neighbor (KNN) model can predict the human‐infecting viruses with an accuracy of over 90%. The performance of this KNN model built on the short contigs (≥1 kb) is comparable to those built on the viral genomes. We used a reported human blood virome to further validate this KNN model with an accuracy of over 80% based on very short raw reads (150 bp). Our work demonstrates a conceptual and generic protocol for the discovery of novel human‐infecting viruses in viral metagenomics studies.
A transcription factor functions differentially and/or identically in multiple cell types. However, the mechanism for cell-specific regulation of a transcription factor remains to be elucidated. We address how a single transcription factor, forkhead box protein A1 (FOXA1), forms cell-specific genomic signatures and differentially regulates gene expression in four human cancer cell lines (HepG2, LNCaP, MCF7, and T47D). FOXA1 is a pioneer transcription factor in organogenesis and cancer progression. Genomewide mapping of FOXA1 by chromatin immunoprecipitation sequencing annotates that target genes associated with FOXA1 binding are mostly common to these cancer cells. However, most of the functional FOXA1 target genes are specific to each cancer cell type. Further investigations using CRISPR-Cas9 genome editing technology indicate that cell-specific FOXA1 regulation is attributable to unique FOXA1 binding, genetic variations, and/or potential epigenetic regulation. Thus, FOXA1 controls the specificity of cancer cell types. We raise a "flower-blooming" hypothesis for cell-specific transcriptional regulation based on these observations.
A B S T R A C TThe African swine fever virus (ASFV) has severely influenced the swine industry of the world. Currently, there is no effective vaccine or drugs against the ASFV. How to effectively control the virus is challenging. In this study, we have analyzed all the publicly available ASFV genomes and demonstrated that there was a large genetic diversity of ASFV genomes. Interestingly, the genetic diversity was mainly caused by extensive genomic insertions and/or deletions (indels) instead of the point mutations. Further analyses showed that the indels may be attributed much to the homologous recombination, as supported by significant associations between the occurrence of extensive recombination events and the indels in the ASFV genomes. Besides, the homologous recombination also led to changes of gene content of ASFVs. Finally, repeated elements of dozens of nucleotides in length were observed to widely distribute and cluster in the adjacent positions of ASFV genomes, which may facilitate the occurrence of homologous recombination. This work highlighted the importance of homologous recombination in shaping the genetic diversity of the ASFVs, and could help understand the evolution of the virus.
Background In modern animal husbandry, breeders pay increasing attention to improving sow nutrition during pregnancy and lactation to favor the health of neonates. Sow milk is a main food source for piglets during their first three weeks of life, which is not only a rich repository of essential nutrients and a broad range of bioactive compounds, but also an indispensable source of commensal bacteria. Maternal milk microorganisms are important sources of commensal bacteria for the neonatal gut. Bacteria from maternal milk may confer a health benefit on the host. Methods Sow milk bacteria were isolated using culturomics followed by identification using 16S rRNA gene sequencing. To screen isolates for potential probiotic activity, the functional evaluation was conducted to assess their antagonistic activity against pathogens in vitro and evaluate their resistance against oxidative stress in damaged Drosophila induced by paraquat. In a piglet feeding trial, a total of 54 newborn suckling piglets were chosen from nine sows and randomly assigned to three treatments with different concentrations of a candidate strain. Multiple approaches were carried out to verify its antioxidant function including western blotting, enzyme activity analysis, metabolomics and 16S rRNA gene amplicon sequencing. Results The 1240 isolates were screened out from the sow milk microbiota and grouped into 271 bacterial taxa based on a nonredundant set of 16S rRNA gene sequencing. Among 80 Pediococcus isolates, a new Pediococcus pentosaceus strain (SMM914) showed the best performance in inhibition ability against swine pathogens and in a Drosophila model challenged by paraquat. Pretreatment of piglets with SMM914 induced the Nrf2-Keap1 antioxidant signaling pathway and greatly affected the pathways of amino acid metabolism and lipid metabolism in plasma. In the colon, the relative abundance of Lactobacillus was significantly increased in the high dose SMM914 group compared with the control group. Conclusion P. pentosaceus SMM914 is a promising probiotic conferring antioxidant capacity by activating the Nrf2-Keap1 antioxidant signaling pathway in piglets. Our study provided useful resources for better understanding the relationships between the maternal microbiota and offspring.
High-throughput reporter assays have been recently developed to directly and quantitatively assess enhancer activity for thousands of regulatory elements. However, there is still no database to collect these enhancers. We developed RAEdb, the first database to collect enhancers identified by high-throughput reporter assays. RAEdb includes 538 320 enhancers derived from eight studies, most of which were from six human cell lines. An activity score was assigned to each enhancer based on reporter assays. Based on these enhancers, 7658 epromoters (promoters with enhancer activity) were identified and stored in the database. RAEdb provides two ways of searches: the first is to search studies by species and cell line; the other is to search enhancers or epromoters by position, activity score, sequence and gene. RAEdb also provides a genome browser to query, visualize and compare enhancers. All data in RAEdb is freely available for download.
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