Biology subjects

Zhao, Q.

Publications and source records attributed to Zhao, Q..

15 recordsLinked to original sources

bioRxiv2018

Using pan RNA-seq analysis to reveal the ubiquitous existence of 5′ end and 3′ end small RNAs

In this study, we used pan RNA-seq analysis to reveal the ubiquitous existence of 5 end and 3 end small RNAs. 5 and 3 sRNAs alone can be used to annotate mitochondrial with 1-bp resolution and nuclear non-coding genes and identify new steady-state RNAs, which are usually from functional genes. Using 5, 3 and intronic sRNAs, we revealed that the enzymatic dsRNA cleavage and RNAi could involve in the RNA degradation and gene expression regulation of U1 snRNA in human. The further study of 5, 3 and intronic sRNAs help rediscover double-stranded RNA (dsRNA) cleavage, RNA interference (RNAi) and the regulation of gene expression, which challenges the classical theories. In this study, we provided a simple and cost effective way for the annotation of mitochondrial and nuclear non-coding genes and the identification of new steady-state RNAs, particularly long non-coding RNAs (lncRNAs). We also provided a different point of view for cancer and virus, based on the new discoveries of dsRNA cleavage, RNAi and the regulation of gene expression.

bioinformatics↗

bioRxiv2018

Designing metabolic division of labor in microbial communities

Microbes face a tradeoff between being metabolically independent and relying on neighboring organisms for the supply of some essential metabolites. This balance of conflicting strategies affects microbial community structure and dynamics, with important implications for microbiome research and synthetic ecology. A \"gedanken experiment\" to investigate this tradeoff would involve monitoring the rise of mutual dependence as the number of metabolic reactions allowed in an organism is increasingly constrained. The expectation is that below a certain number of reactions, no individual organism would be able to grow in isolation, and cross-feeding partnerships and division of labor would emerge. We implemented this idealized experiment using in silico genome-scale models. In particular, we used mixed integer linear programming to identify tradeoff solutions in communities of Escherichia coli strains. The strategies we found reveal a large space of nuanced and nonintuitive metabolic division of labor opportunities, including, for example, splitting the TCA cycle into two separate halves. The systematic computation of possible division of labor solutions for 1-, 2-, and 3-strain consortia resulted in a rich and complex landscape. This landscape displays a nonlinear boundary, indicating that the loss of an intracellular reaction is not necessarily compensated by a single imported metabolite. Different regions in this landscape are associated with specific solutions and patterns of exchanged metabolites. Our approach also predicts the existence of regions in this landscape where independent bacteria are viable, but outcompeted by cross-feeding pairs, providing a possible incentive for the rise of division of labor.

systems biology↗

bioRxiv2018

Exploratory Gene Ontology Analysis with Interactive Visualization

The Gene Ontology (GO) is a central resource for functional-genomics research. Scientists rely on the functional annotations in the GO for hypothesis generation and couple it with high-throughput biological data to enhance interpretation of results. At the same time, the sheer number of concepts (>30,000) and relationships (>70,000) presents a challenge: it can be difficult to draw a comprehensive picture of how certain concepts of interest might relate with the rest of the ontology structure. Here we present new visualization strategies to facilitate the exploration and use of the information in the GO. We rely on novel graphical display and software architecture that allow significant interaction. To illustrate the potential of our strategies, we provide examples from high-throughput genomic analyses, including chromatin immunoprecipitation experiments and genome-wide association studies. The scientist can also use our visualizations to identify gene sets that likely experience coordinated changes in their expression and use them to simulate biologically-grounded single cell RNA sequencing data, or conduct power studies for differential gene expression studies using our built-in pipeline. Our software and documentation are available at http://aegis.stanford.edu.

bioinformatics↗

bioRxiv2018

Hetero-oligomeric CPN60 resembles highly symmetric group I chaperonin structure revealed by Cryo-EM

The chloroplast chaperonin system is indispensable for the biogenesis of Rubisco, the key enzyme in photosynthesis. Using Chlamydomonas reinhardtii as the model system, we revealed that chloroplast chaperonin is consisted of CPN60, CPN60{beta}1, and CPN60{beta}2, and co-chaperonin is composed of three subunits CPN20, CPN11 and CPN23 in vivo. CPN20 homo-oligomers and all possible other chloroplast co-chaperonin hetero-oligomers are functional, but only CPN11/20/23-CPN60{beta}1{beta}2 pair can fully replace GroES/GroEL in E. coli at stringent growth condition. Endogenous CPN60 was purified and its stoichiometry was determined to be 6:2:6 for CPN60:CPN60{beta}1:CPN60{beta}2. The cryo-EM structures of endogenous CPN60{beta}1{beta}2/ADP and CPN60{beta}1{beta}2/co-chaperonin/ADP were solved at resolutions of 4.06 [A] and 3.82[A], respectively. In both hetero-oligomeric complexes the chaperonin subunits within each ring are highly symmetric. The chloroplast co-chaperonin CPN11/20/23 formed seven GroES-like domains through hetero-oligomerization which symmetrically interact with CPN60{beta}1{beta}2. Our structures also reveal an uneven distribution of roof-like structures in the dome-shaped CPN11/20/23 and potentially diversified surface properties in the folding cavity of CPN60{beta}1{beta}2 that might enable the chloroplast chaperonin system to assist in the folding of specific substrates.

biochemistry↗

bioRxiv2018

A draft reference genome sequence for Scutellaria baicalensis Georgi

Scutellaria baicalensis Georgi is an important medicinal plant used worldwide. Information about the genome of this species is important for scientists studying the metabolic pathways that synthesise the bioactive compounds in this plant. Here, we report a draft reference genome sequence for S. baicalensis obtained by a combination of Illumina and PacBio sequencing, which was assembled using 10 X Genomics and Hi-C technologies. We assembled 386.63 Mb of the 408.14 Mb genome, amounting to about 94.73% of the total genome size, and the sequences were anchored onto 9 pseudochromosomes with a super-N50 of 33.2 Mb. The reference genome sequence of S. baicalensis offers an important foundation for understanding the biosynthetic pathways for bioactive compounds in this medicinal plant and for its improvement through molecular breeding.

plant biology↗

bioRxiv2018

Circular RNAs regulate cancer stem cells by FMRP against CCAR1 complex in hepatocellular carcinoma

Circular RNA (circRNA) possesses great pre-clinical diagnostic and therapeutic potentials in multiple cancers. However, the underlying correlation between circRNAs and cancer stem cells (CSCs) has not been reported. The absence of circZKSCAN1 endowed several malignant properties including cancer stemness and tightly correlated with worse overall and recurrence-free survival rate in HCC cells in vitro and in vivo. Bioinformatics analysis and RNA immunoprecipitation-sequencing (RIP-seq) results revealed that circZKSCAN1 exerted its inhibitive role by competitively binding FMRP, therefore, block the binding between FMRP and {beta}-catenin-binding protein-cell cycle and apoptosis regulator 1 (CCAR1) mRNA, and subsequently restraining the transcriptional activity of Wnt signaling. In addition, RNA-splicing protein Quaking 5 was found downregulated in HCC tissues and responsible for the reduction of circZKSCAN1. Collectively, this study revealed the mechanisms underlying the regulatory role of circZKSCAN1 in HCC CSCs and identified the newly discovered Qki5- circZKSCAN1-FMRP-CCAR1-Wnt signaling axis as a potentially important therapeutic target for HCC treatment.\n\nStatement of significanceO_LICircZKSCAN1, a novel negative regulator for cancer stem cells, was firstly identified with reverse correlation with HCC prognosis.\nC_LIO_LICircZKSCAN1 directly targets FMRP, and competitive binding with {beta}-catenin-binding protein cell cycle and apoptosis regulator 1 (CCAR1) for its activity.\nC_LIO_LIThe decreased expression of Quaking 5 is responsible for the absence of circZKSCAN1 in HCC.\nC_LI

cancer biology↗

bioRxiv2018

Identification, Genotyping, and Pathogenicity of Trichosporon spp. Isolated from Giant Pandas

Trichosporon is the dominant genus of epidermal fungi in giant pandas and causes local and deep infections. To provide the information needed for the diagnosis and treatment of trichosporosis in giant pandas, the sequence of ITS, D1/D2, and IGS1 loci in 29 isolates of Trichosporon spp. which isolated from the body surface of giant pandas were combination to investigate interspecies identification and genotype. Morphological development was examined via slide culture. Additionally, mice were infected by skin inunction, intraperitoneal injection, and subcutaneous injection for evaluation of pathogenicity. The twenty-nine isolates of Trichosporon spp. were identified as belonging to 11 species, and Trichosporon jirovecii and T. asteroides were the commonest species. Four strains of T. laibachii and one strain of T. moniliiforme were found to be of novel genotypes, and T. jirovecii was identified to be genotype 1. T. asteroides had the same genotype which involved in disseminated trichosporosis. The morphological development processes of the Trichosporon spp. were clearly different, especially in the processes of single-spore development. Pathogenicity studies showed that 7 species damaged the liver and skin in mice, and their pathogenicity was stronger than other 4 species. T. asteroides had the strongest pathogenicity and might provoke invasive infection. The pathological characteristics of liver and skin infections caused by different Trichosporon spp. were similar. So it is necessary to identify the species of Trichosporon on the surface of giant panda. Combination of ITS, D1/D2, and IGS1 loci analysis, and morphological development process can effectively identify the genotype of Trichosporon spp.

microbiology↗

bioRxiv2018

IDEA: a web server for Interactive Differential Expression Analysis with R Packages

Differential expression (DE) analysis is a fundamental task in the downstream analysis of the next-generation sequencing (NGS) data. Up to now, a number of R packages have been developed for detecting differentially expressed genes. Although R language has an interaction-oriented programming design, for many biology researchers, a lack of basic programming skills has greatly hindered the application of these R packages. To address this issue, we developed the Interactive Differential Expression Analyzer (IDEA), a Shiny-based web application integrating the differential expression analysis related R packages into a graphical user interface (GUI), allowing users to run the analysis without writing any new code. A wide variety of charts and tables are generated to facilitate the interpretation of the results. In addition, IDEA also provides a combined analysis framework which helps to reconcile any discrepancy from different computational methods. As a public data analysis server, IDAE is implemented in HTML, CSS and JavaScript, and is freely available at http://idea.renlab.org.

bioinformatics↗

bioRxiv2018

Verification of the phenylpropanoid pinoresinol biosynthetic pathway and its glycosides in Phomopsis sp. XP-8 using 13C stable isotope labeling and liquid chromatography coupled with time-of-flight mass spectrometry

Phomopsis sp. XP-8, an endophytic fungus from the bark of Tu-Chung (EucommiaulmoidesOliv), revealed the pinoresinol diglucoside (PDG) biosynthetic pathway after precursor feeding measurements and genomic annotation. To verify the pathway more accurately, [13C6]-labeled glucose and [13C6]-labeled phenylalanine were separately fed to the strain as sole substrates and [13C6]-labeled products were detected by ultra-high performance liquid chromatography-quantitative time of flight mass spectrometry. As results, [13C6]-labeled phenylalanine was found as [13C6]-cinnamylic acid and p-coumaric acid, and [13C12]-labeled pinoresinol revealed that the pinoresinol benzene ring came from phenylalanine via the phenylpropane pathway. [13C6]-Labeled cinnamylic acid and p-coumaric acid, [13C12]-labeled pinoresinol, [13C18]-labeled pinoresinol monoglucoside (PMG), and [13C18]-labeled PDG products were found when [13C6]-labeled glucose was used, demonstrating that the benzene ring and glucoside of PDG originated from glucose. It was also determined that PMG was not the direct precursor of PDG in the biosynthetic pathway. The study verified the occurrence of the plant-like phenylalanine and lignan biosynthetic pathway in fungi.\n\nImportanceVerify the phenylpropanoid-pinoresinol biosynthetic pathway and its glycosides in an endophytic fungi.

microbiology↗

bioRxiv2018

Predict plant-derived xenomiRs from plant miRNA sequences using random forest and one-dimensional convolutional neural network models

BackgroundAn increasing number of studies reported that exogenous miRNAs (xenomiRs) can be detected in animal bodies, however, some others reported negative results. Some attributed this divergence to the selective absorption of plant-derived xenomiRs by animals.\n\nResultsHere, we analyzed 166 plant-derived xenomiRs reported in our previous study and 942 non-xenomiRs extracted from miRNA expression profiles of four species of commonly consumed plants. Employing statistics analysis and cluster analysis, our study revealed the potential sequence specificity of plant-derived xenomiRs. Furthermore, a random forest model and a one-dimensional convolutional neural network model were trained using miRNA sequence features and raw miRNA sequences respectively and then employed to predict unlabeled plant miRNAs in miRBase. A total of 241 possible plant-derived xenomiRs were predicted by both models. Finally, the potential functions of these possible plant-derived xenomiRs along with our previously reported ones in human body were analyzed.\n\nConclusionsOur study, for the first time, presents the systematic plant-derived xenomiR sequences analysis and provides evidence for selective absorption of plant miRNA by human body, which could facilitate the future investigation about the mechanisms underlying the transference of plant-derived xenomiR.

bioinformatics↗

bioRxiv2017

Insights into DNA substrate selection by APOBEC3G from structural, biochemical, and functional studies.

Human apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 (A3) proteins are a family of cytidine deaminases that catalyze the conversion of cytidine to uridine in single-stranded DNA (ssDNA). A3 proteins act in the innate immune response to viral infection by mutating the viral ssDNA. One of the most well-studied human A3 family members is A3G, which is a potent inhibitor of HIV-1. Each A3 protein prefers a specific substrate sequence for catalysis - for example, A3G deaminates the third cytidine in the CCCA sequence motif. However, the interaction between A3G and ssDNA is difficult to characterize due to poor solution behavior of the full-length protein and loss of DNA affinity of the truncated protein. Here, we present a novel DNA-anchoring fusion strategy, which we have used to capture an A3G-ssDNA interaction. We characterized an A3G-DNA binding pocket that is important for the enzyme to scan the DNA for its hotspot. The results provide insights into the mechanism by which A3G selects and deaminates its preferred substrates and help define how A3 proteins are tailored to recognize specific DNA sequences. This knowledge contributes to a better understanding of the mechanism of DNA substrate selection by A3G, as well as A3G antiviral activity against HIV-1.

biophysics↗

bioRxiv2017

Insm1a regulates motor neuron development in zebrafish

Insulinoma-associated1a (Insm1a) is a zinc-finger transcription factor playing a series of functions in cell formation and differentiation of vertebrate central and peripheral nervous systems and neuroendocrine system. However, its roles on the development of motor neuron have still remained uncovered. Here, we provided evidences that insmla was a vital regulator of motor neuron development and provide a mechanistic understanding of how it contributes to this process. Firstly, we showed the localization of insmla in spinal cord and primary motor neurons (PMNs) of zebrafish embryos by in situ hybridization and imaging analysis of transgenic reporter line Tg(insmla: mCherry) ntu805. Then we demonstrated that the deficiency of insmla in zebrafish larvae lead to the defects of PMNs development, including the reduction of caudal primary motor neurons (CaP) and middle primary motor neurons (MiP), the excessive branching of motor axons, and the disorganized distance between adjacent CaPs. Additionally, knockout of insm1 impaired motor neuron differentiation in the spinal cord. Locomotion analysis showed that insmla-null zebrafish significantly reduced the swimming activity. Furthermore, we proved that the insmla loss of function significantly decreased the transcripts levels of both olig2 and nkx6.1. Microinjection of olig2 and nkx6.1 mRNA rescued the motor neuron defects in insmla deficient embryos. Taken together, these data indicate that insmla regulates the motor neuron development, at least in part, through modulation of the expressions of olig2 and nkx6.1.

developmental biology↗

bioRxiv2017

A functional role for the epigenetic regulator ING1 in activity-induced gene expression in primary cortical neurons

Epigenetic regulation of activity-induced gene expression involves multiple levels of molecular interaction, including histone and DNA modifications, as well as mechanisms of DNA repair. Here we demonstrate that the genome-wide deposition of Inhibitor of growth family member 1 (ING1), which is a central epigenetic regulatory protein, is dynamically regulated in response to activity in primary cortical neurons. ING1 knockdown leads to decreased expression of genes related to synaptic plasticity, including the regulatory subunit of calcineurin, Ppp3r1. In addition, ING1 binding at a site upstream of the transcription start site (TSS) of Ppp3r1 depends on yet another group of neuroepigenetic regulatory proteins, the Piwi-like family, which are also involved in DNA repair. These findings provide new insight into a novel mode of activity-induced gene expression, which involves the interaction between different epigenetic regulatory mechanisms traditionally associated with gene repression and DNA repair.\n\nAuthor contributionsL.J.L., Q.Z., T.W.B and W.W. designed the experiments. N.K., A.K., X.L., C.D., S.L. and W.W. designed and assembled shRNA constructs. L.J.L., W.W., X.L., C.D., P.R.M., E.Z., and S.L. conducted experiments. Q.Z. and Y.W. analysed ChIP-seq data. L.J.L., Q.Z., and W.W. wrote the paper. All authors reviewed and edited the manuscript.\n\nConflicts of interestNone.

neuroscience↗

bioRxiv2017

Deficiency of Voltage-gated Proton Channel Hv1 Leads to hypoinsulinaemia, hyperglycemia and glucose intolerance in mice

Here, we demonstrate that the voltage-gated proton channel Hv1 represents a regulatory mechanism for insulin secretion of pancreatic islet {beta} cell. In vivo, Hv1-de[fi]cient mice display hyperglycemia and glucose intolerance due to reduced insulin secretion, but normal peripheral insulin sensitivity. In vitro, islets of Hv1-de[fi]cient and heterozygous mice, INS-1 (832/13) cells with siRNA-mediated knockdown of Hv1 exhibit a marked defect in glucose- and K+-induced insulin secretion. Hv1 de[fi]ciency decreases both insulin and proinsulin contents, and limits glucose-induced Ca2+ entry and membrane depolarization. Furthermore, loss of Hv1 increases insulin-containing granular pH and decreases cytosolic pH. In addition, histologic studies show a decrease in {beta} cell mass in islets of Hv1-deficient mice. Collectively, our results indicate that Hv1 supports insulin secretion in the {beta} cell by calcium entry, membrane depolarization and intracellular pH regulation.

cell biology↗

bioRxiv2016

Genetic footprint of population fragmentation and contemporary collapse in a freshwater cetacean

Understanding demographic trends and patterns of gene flow in an endangered species is crucial for devising conservation strategies. Here, we examined the extent of population structure and recent evolution of the critically endangered Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis). By analysing genetic variation at the mitochondrial and nuclear microsatellite loci for 148 individuals, we identified three populations along the Yangtze River, each one connected to a group of admixed ancestry. Each population displayed extremely low genetic diversity, consistent with extremely small effective size ([≤]92 individuals). Habitat degradation and distribution gaps correlated with highly asymmetric gene-flow that was inefficient in maintaining connectivity between populations. Genetic inferences of historical demography revealed that the populations in the Yangtze descended from a small number of founders colonizing the river from the sea during the last Ice Age. The colonization was followed by a rapid population split during the last millennium predating the Chinese Modern Economy Development. However, genetic diversity showed a clear footprint of population contraction over the last 50 years leaving only ~2% of the pre-collapsed size, consistent with the population collapses reported from field studies. This genetic perspective provides background information for devising mitigation strategies to prevent this species from extinction.

evolutionary biology↗