Biology subjects

Wu, A.

Publications and source records attributed to Wu, A..

5 recordsLinked to original sources

bioRxiv2018

Identification of genome-wide nucleotide sites associated with mammalian virulence in influenza A viruses

MotivationThe virulence of influenza viruses is a complex multigenic trait. Previous studies about the virulence determinants of influenza viruses mainly focused on amino acid sites, ignoring the influence of nucleotide mutations.\n\nResultsWe collected more than 200 viral strains from 21 subtypes of influenza A viruses with virulence in mammals and obtained over 100 mammalian virulence-related nucleotide sites across the genome by computational analysis. Interestingly, 50 of these nucleotide sites only experienced synonymous mutations. Further experiments showed that synonymous mutations in the top two of these nucleotide sites, i.e., PB1-2031 and PB1-633, enhanced the pathogenicity of the viruses in mice. Finally, machine-learning models with accepted accuracy for predicting mammalian virulence of influenza A viruses were built. Overall, this study highlighted the importance of nucleotide mutations, especially synonymous mutations in viral virulence, and provided rapid methods for evaluating the virulence of influenza A viruses. It could be helpful for early warning of newly emerging influenza A viruses.

microbiology↗

bioRxiv2018

Non-adhesive alginate hydrogels support growth of pluripotent stem cell-derived intestinal organoids

Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. Experimental control and clinical use of HIOs is limited by growth in expensive and poorly defined tumor-cell-derived extracellular matrices, prompting investigation of synthetic ECM-mimetics for HIO culture. Since HIOs possess an inner epithelium and outer mesenchyme, we hypothesized that adhesive cues provided by the matrix may be dispensable for HIO culture. Here, we demonstrate that alginate, a minimally supportive hydrogel with no inherent cell adhesion properties, supports HIO growth in vitro and leads to HIO epithelial differentiation that is virtually indistinguishable from Matrigel-grown HIOs. Additionally, alginate-grown HIOs mature to a similar degree as Matrigel-grown HIOs when transplanted in vivo, both resembling human fetal intestine. This work demonstrates that purely mechanical support from a simple-to-use and inexpensive hydrogel is sufficient to promote HIO survival and development.

developmental biology↗

bioRxiv2018

Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors

Receptor mediated entry is the first step for viral infection. However, the relationship between viruses and receptors is still obscure. Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors were structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. Additionally, the receptors used by the same virus tended to co-evolve. Further correlation analysis between viral receptors and the tissue and host specificity of the virus shows that the virus receptor similarity was a significant predictor for mammalian virus cross-species. This work could deepen our understanding towards the viral receptor selection and help evaluate the risk of viral zoonotic diseases.

microbiology↗

bioRxiv2018

Reducing False Positives in CRISPR/Cas9 Screens from Copy Number Variations

CRISPR/Cas9 knockout screens have been widely used to interrogate gene functions across a wide range of cell systems. However, the screening outcome is biased in amplified genomic regions, due to the ability of the Cas9 nuclease to induce multiple double-stranded breaks and strong DNA damage responses at these regions. We developed algorithms to correct biases associated with copy number variations (CNV), even when the CNV profiles are unknown. We demonstrated that our methods effectively reduced false positives in amplified regions while preserving signals of true positives. In addition, we developed a sliding window approach to estimate regions of high copy numbers for cases in which CNV information is not available. These copy number estimations can subsequently be used to effectively correct CNV-related biases in CRISPR screening experiments. Our approach is integrated into the existing MAGeCK/MAGeCK-VISPR analysis pipelines and provides a convenient framework to improve the precision of CRISPR screening results.

bioinformatics↗

bioRxiv2017

Gut Microbiota Composition Related With Clostridium difficile-Positive Diarrhea And C. Difficile Type (A+B+, A-B+, And A-B-) In ICU Hospitalized Patients

BackgroundGut microbiota composition of intensive care unit (ICU) patients suffering from Clostridium difficile-positive diarrhea (CDpD) is still poorly understood. This study aims to use 16S rDNA (and metagenome) sequencing to compare the microbiota composition of 58 (and 5) ICU patients with CDpD (CDpD group), 33 (and 4) ICU patients with C. difficile negative diarrhea (CDnD group), and 21 (and 5) healthy control subjects (control group), as well as CDpD patients in A+B+ (N=34; A/B: C. difficile TcdA/B), A-B+ (N=7), and A-B- (N=17) subgroups. For 16S rDNA data, OTU clustering (tool: UPARSE), taxonomic assignment (tool: RDP classifier), -diversity and {beta}-diversity analyses (tool: QIIME) were conducted. For metagenome data, metagenome assembly (tool: SOAP), gene calling (tools: MetaGeneMark, CD-HIT, and SoapAligner), unigene alignment (tool: DIAMOND), taxon difference analysis (tool: Metastats), and gene annotation (tool: DIAMOND) were performed.\n\nResultsThe microbial diversity of CDpD group was lower than that of CDnD and control groups. The abundances of 10 taxa (e.g. Deferribacteres, Cryptomycota, Acetothermia) in CDpD group were significantly higher than that in CDnD group. The abundances of Saccharomycetes and Clostridia were significantly lower in CDpD in comparison with control. A+B+, A-B+ and A-B- subgroups couldnt be separated in principal component analysis, while some taxa are significantly different between A+B+ and A-B- subgroups.\n\nConclusionCDpD might relate to the decrease of beneficial taxa (i.e. Saccharomycetes and Clostridia) and the increase of harmful taxa (e.g. Deferribacteres, Cryptomycota, Acetothermia) in gut microbiota in ICU patients. C. difficile type might be slightly associated with gut microbiota composition.

molecular biology↗