Biology subjects

Qiu, W.

Publications and source records attributed to Qiu, W..

72 records · Page 4Linked to original sources

bioRxiv2020

CoV Genome Tracker: tracing genomic footprints of Covid-19 pandemic

SummaryGenome sequences constitute the primary evidence on the origin and spread of the 2019-2020 Covid-19 pandemic. Rapid comparative analysis of coronavirus SARS-CoV-2 genomes is critical for disease control, outbreak forecasting, and developing clinical interventions. CoV Genome Tracker is a web portal dedicated to trace Covid-19 outbreaks in real time using a haplotype network, an accurate and scalable representation of genomic changes in a rapidly evolving population. We resolve the direction of mutations by using a bat-associated genome as outgroup. At a broader evolutionary time scale, a companion browser provides gene-by-gene and codon-by-codon evolutionary rates to facilitate the search for molecular targets of clinical interventions. Availability and ImplementationCoV Genome Tracker is publicly available at http://cov.genometracker.org and updated weekly with the data downloaded from GISAID (http://gisaid.org). The website is implemented with a custom JavaScript script based on jQuery (https://jquery.com) and D3-force (https://github.com/d3/d3-force). Contactweigang@genectr.hunter.cuny.edu, City University of New York, Hunter College Supplementary InformationAll supporting scripts developed in JavaScript, Python, BASH, and PERL programming languages are available as Open Source at the GitHub repository https://github.com/weigangq/cov-browser.

evolutionary biology↗

bioRxiv2020

Postpartum fluoxetine increased maternal hippocampal IL-1β and decreased plasma tryptophan: clues for efficacy

Perinatal depression (PND) affects approximately 15% of women, and de novo postpartum depression affects approximately 40% of PND cases. Selective serotonin reuptake inhibitors (SSRIs) are a common class of antidepressants prescribed to treat PND. However, the safety and efficacy of SSRIs have been questioned in both clinical and preclinical research. Here, using a preclinical rodent model of postpartum depression, we aim to better understand neuroinflammatory cytokines and tryptophan mechanisms that may be related to SSRIs efficacy. Rodent dams were treated with high corticosterone (CORT; 40mg/kg, s.c.) for 21 days in the postpartum period to simulate depressive-like behaviors in the late postpartum period. Concurrently, a subset of dams was treated with the SSRI, fluoxetine (FLX; 10mg/kg, s.c.), in the postpartum period. We showed, consistent with previous studies, that although maternal FLX treatment prevented CORT-induced disturbances in maternal care behavior during the early postpartum, it failed to prevent the expression of CORT-induced depressive-like behavior in the late postpartum. Furthermore, FLX treatment, regardless of CORT treatment, increased maternal hippocampal IL-1{beta} and decreased maternal plasma tryptophan levels, plasma tryptophan, 4-pyridoxic acid, and pyridoxal concentrations. Maternal CORT treatment reduced maternal hippocampal TNF- and IFN-{gamma} levels. Our work suggests that the limited efficacy of FLX in the late postpartum may be associated with elevated levels of the proinflammatory cytokine IL-1{beta} in the maternal hippocampus, decreased plasma tryptophan concentration, and changes in vitamin B6 dependent tryptophan-kynurenine pathway. These findings suggest novel pathways for improving SSRI efficacy in alleviating perinatal depression. HIGHLIGHTSO_LIPostpartum fluoxetine (FLX) increased interleukin-1{beta} levels in hippocampus C_LIO_LIPostpartum corticosterone (CORT) decreased TNF- and IFN-{gamma} in the hippocampus C_LIO_LIPostpartum FLX did not prevent CORT-induced depressive-like behavior C_LIO_LIPostpartum FLX prevented CORT-induced changes in maternal behavior C_LIO_LIPostpartum FLX decreased plasma tryptophan, 4-pyridoxic acid, and pyridoxal levels C_LI

neuroscience↗

bioRxiv2020

Generalizability of "GWAS hits" in clinical populations: Lessons from childhood cancer survivors

With mounting interest in translating GWAS hits from large meta-analyses (meta-GWAS) in diverse clinical settings, evaluating their generalizability in target populations is crucial. Here we consider long-term survivors of childhood cancers from the St. Jude Lifetime Cohort Study and show the limited generalizability of 1,376 robust SNP associations reported in the general population across 12 complex anthropometric and cardiometabolic phenotypes (N=2,231; observed-to-expected replication ratio=0.68, P=2.4x10-9). An examination of five comparable phenotypes in a second independent cohort of survivors from the Childhood Cancer Survivor Study corroborated the overall limited generalizability of meta-GWAS hits to survivors (N=4,212, observed-to-expected replication ratio=0.53, P=1.1x10-16). Meta-GWAS hits were less likely to be replicated in survivors exposed to cancer therapies associated with phenotype risk. Examination of complementary DNA methylation data in a subset of survivors revealed that treatment-related methylation patterns at genomic sites linked to meta-GWAS hits may disrupt established genetic signals in survivors.

genetics↗

bioRxiv2019

Oxytocin has sex-specific effects on social behaviour and hypothalamic oxytocin immunoreactive cells but not hippocampal neurogenesis in adult rats.

Oxytocin regulates social behaviours, pair bonding and hippocampal neurogenesis but most studies have used adult males. Our study investigated the effects of oxytocin on social investigation and adult hippocampal neurogenesis in male and female rats. Oxytocin has poor penetration of the blood-brain barrier, therefore we tested a nanoparticle drug, TRIOZANTM (Ovensa Inc.), which permits greater blood-brain-barrier penetration. Adult male and female rats were injected daily (i.p.) for 10 days with either: oxytocin in PBS (0.5 or 1.0 mg/kg), oxytocin in TRIOZANTM (0.5 or 1.0 mg/kg), or vehicle (PBS) and tested for social investigation. Oxytocin decreased body mass and increased social investigation and number of oxytocin-immunoreactive cells in the supraoptic nucleus (SON) of the hypothalamus in male rats only. In both sexes, oxytocin decreased the number of immature neurons (doublecortin+ cells) in the ventral hippocampus and reduced plasma 17{beta}-estradiol levels in a dose- and delivery-dependent way. Oxytocin in TRIOZANTM reduced sedation observed post-injection and increased some central effects (oxytocin levels in the hypothalamus and ventral hippocampus neurogenesis) relative to oxytocin in PBS indicating that the nanoparticle may be used as an alternative brain delivery system. We showed that oxytocin has sex-specific effects on social investigation, body mass, sedation, and the oxytocin system. In contrast, similar effects were observed in both sexes in neurogenesis and plasma 17{beta}-estradiol. Our work suggests that sex differences in oxytocin regulation of brain endpoints is region-specific (hypothalamus versus hippocampus) and that oxytocin does not promote social investigation in females.

neuroscience↗

bioRxiv2019

MACF1 Facilitates SMAD7 Nuclear Translocation to Drive Bone Formation in Mice

MACF1 is a large crosslinker that contributes to cytoskeleton integrity and cell differentiation. Loss of MACF1 impairs multiple cellular functions in neuron development and epidermal migration, and is the molecular basis for many diseases such as heart failure and Parkinsons disease. MACF1 is highly abundant in bones, however, its involvements in osteogenic differentiation and bone formation are still unknown. In this study, by conditional gene targeting to delete the Macf1 gene specifically in MSCs, we observed ossification retardation and bone loss in MACF1 deficient mice in different developmental stages, which we traced to disorganized cytoskeleton and decreased osteogenic differentiation capability in MSCs. Further, we show that MACF1 interacts and facilitates SMAD7 nuclear translocation to initiate downstream transcription. These findings are hopefully to expand the biological scope of MACF1 in bones, and provide experimental basis for targeting MACF1 in degenerative bone diseases such as osteoporosis.

developmental biology↗

bioRxiv2018

Dietary folic acid increases neurogenesis in the ventral hippocampus of adult female rats

Folate is an important regulator of hippocampal neurogenesis, and in utero spinal cord development. Both high levels of folic acid and low levels of folate can be harmful to health, as low levels of folate have been linked to several diseases while high folic acid supplements can mask a vitamin B12 deficiency. Depressed patients exhibit folate deficiencies, lower levels of hippocampal neurogenesis, elevated levels of homocysteine, and elevated levels of the stress hormone, cortisol, which may be inter-related. Here, we are interested in whether different doses of natural folate or synthetic folic acid diets can influence neurogenesis in the hippocampus, levels of plasma homocysteine, and serum corticosterone in adult female rats. Adult female Sprague-Dawley rats underwent dietary interventions for 29 days. Animals were randomly assigned to six different dietary groups: folate deficient + succinylsulfathiazole (SST), low 5-methyltetrahydrofolate (5-MTHF), low 5-MTHF + (SST), high 5-MTHF + SST, low folic acid, and high folic acid. SST was added to a subset of the 5-MTHF diets to eliminate folic acid production in the gut. Before and after dietary treatment, blood samples were collected for corticosterone and homocysteine analysis, and brain tissue was collected for neurogenesis analysis. High folic acid and low 5-MTHF without SST increased the number of immature neurons (doublecortin-expressing cells) within the ventral hippocampus compared to folate deficient controls. Low 5-MTHF without SST significantly increased the number of immature neurons compared to low and high 5-MTHF + SST, indicating that SST interfered with elevations in neurogenesis. Low folic acid and high 5-MTHF+SST reduced plasma homocysteine levels compared to controls, but there was no significant effect of diet on serum corticosterone levels. Low folic acid and high 5-MTHF+SST reduced the number of mature new neurons in the ventral hippocampus (BrdU/NeuN-positive cells) compared to folate deficient controls. Overall, folic acid dose-dependently influenced neurogenesis, with low levels decreasing but high levels increasing, neurogenesis in the ventral hippocampus, suggesting this region, which is important for regulating stress, is particularly sensitive to folic acid in diets. Furthermore, the addition of SST negated the effects of 5-MTHF to increase neurogenesis in the ventral hippocampus.

neuroscience↗

bioRxiv2018

Novel Data Transformations for RNA-seq Data Analysis

We propose eight data transformations for RNA-seq data analysis aiming to make the transformed sample mean to be representative of the distribution center since it is not always possible to transform count data to satisfy the normality assumption. Simulation studies showed that limma based on transformed data by using the rv transformation (denoted as limma+rv) performed best compared with limma based on transformed data by using other transformation methods in term of high accuracy and low FNR, while keeping FDR at the nominal level. For large sample size, limma based on transformed data by using the 8 proposed transformation methods had similar performance to limma based on transformed data by using existing transformation methods for equal library size scenarios. Otherwise, limma based on transformed data by using the rv, lv, rv2, or lv2 transformation, or by using the existing voom transformation performed better than limma based on data from other transformation methods. Real data analysis results showed that limma+ l2 performed best, while limma+ rv also had good performance.

bioinformatics↗

bioRxiv2018

The Orphan Kinesin PAKRP2 Achieves Processive Motility Via Noncanonical Stepping

PAKRP2 is an orphan kinesin in Arabidopsis thaliana that is thought to transport vesicles along phragmoplast microtubules for cell plate formation. Here, using single-molecule fluorescence microscopy, we show that PAKRP2 exhibits processive plus-end-directed motility on single microtubules as individual homodimers despite having an exceptionally long (32 residues) neck linker. Furthermore, using high-resolution nanoparticle tracking to visualize motor stepping dynamics, we find that PAKRP2 achieves processivity via a noncanonical stepping mechanism that includes small step sizes and frequent lateral steps to adjacent protofilaments. We propose that the small steps sizes are due to a transient intermediate step that involves a prolonged diffusional search of the tethered head due to its long neck linker. Despite this different stepping behavior, ATP is tightly coupled to each 8-nm step. Collectively, this study reveals PAKRP2 as the first orphan kinesin to demonstrate processive motility and broadens our understanding of the diverse kinesin stepping mechanisms.

biophysics↗

bioRxiv2018

Noninvasive prenatal test of methylmalonic academia cblC type through targeted sequencing of cell-free DNA in maternal plasma

Methylmalonic acidemia (MMA) cblC type is the most frequent inborn error of intracellular cobalamin metabolism which is caused by mutations of MMACHC gene. Non-invasive test of MMA for pregnant women facilitates safe and timely prenatal diagnosis of the disease. In our study, we aimed to design and validate a haplotype-based noninvasive prenatal test (NIPT) method for cblC type of MMA. Targeted capture sequencing using customized hybridization was performed utilizing gDNA (genomic DNA) of trios including parents and an affected proband to determine parental haplotypes associated with the mutant and wild allele. The fetal haplotype was inferred later based on the high depth sequencing data of maternal plasma as well as haplotype linkage analysis. The fetal genotypes deduced by NIPT were further validated by amniocentesis. Haplotype-based NIPT was successfully performed in 21 families. The results of NIPT of 21 families were all consistent with invasive prenatal diagnosis, which was interpreted in a blinded fashion. Three fetuses were identified as compound heterozygosity of MMACHC, 9 fetuses were carriers of MMACHC variant, and 9 fetuses were normal. These results indicated that the haplotype-based NIPT for MMA through small target capture region sequencing is technically accurate and feasible.

genetics↗

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

New Statistical Methods for Constructing Robust Differential Correlation Networks

The interplay among microRNAs (miRNAs) plays an important role in the developments of complex human diseases. Co-expression networks can characterize the interactions among miRNAs. Differential correlation network is a powerful tool to investigate the differences of co-expression networks between cases and controls. To construct a differential correlation network, the Fishers Z-transformation test is usually used. However, the Fishers Z-transformation test requires the normality assumption, the violation of which would result in inflated Type I error rate. Several bootstrapping-based improvements for Fishers Z test have been proposed. However, these methods are too computationally intensive to be used to construct differential correlation networks for high-throughput genomic data. In this article, we proposed six novel robust equal-correlation tests that are computationally efficient. The systematic simulation studies and a real microRNA data analysis showed that one of the six proposed tests (ST5) overall performed better than other methods.

bioinformatics↗

bioRxiv2018

Introduce a New Approach to Detect Genes Associated to Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) represents the most frequent of all oral neoplasms in the world. Genetics plays an important role in the etiopathogenesis of OSCC. However, the investigation of the molecular mechanism of OSCC is still incomplete. In this article, we introduced a new approach to detect OSCC-associated genes, in which we not only compare mean difference, but also variance difference between cases and controls. Based on two OSCC datasets from Gene Expression Omnibus, we identified 456 differentially variable (DV) gene probes, in addition to 2,375 differentially expressed (DE) gene probes. There are 2,193 DE-only probes, 274 DV-only probes, and 182 DE-and-DV probes. DAVID functional analysis showed that genes corresponding to DE-only, DV-only, and DE-and-DV probes were enriched in different KEGG pathways, indicating they play different roles in OSCC. This new approach can be used to investigate the genetic risk factors for other complex human diseases.

genetics↗

bioRxiv2018

The Association between Alcohol Consumption and Telomere Length: A Meta-Analysis Focusing on Observational Studies

BackgroundBoth telomere length and alcohol consumption play important roles in carcinogenesis and biological age. Many efforts have been made to investigate the association between alcohol consumption and telomere length. However, no consensus has been reached yet.\n\nMethodsIn this article, we performed a meta-analysis to integrate the investigation results in the literature about the association between alcohol consumption and telomere length. After searching articles published between 2000 and 2016, 21 articles (including 27 analyses, total sample size 35,891) met our eligibility criteria.\n\nResultsWe found a significant association between alcohol consumption and telomere length (Fishers combined p-value = 3.52E-8 and Liptaks weighted p-value = 8.24E-3). We also found that the significance of the association between alcohol consumption and telomere length varies with study type (cohort, case-control, or cross-sectional) and study population (Europe, Asia, American, or Australia).\n\nConclusionsCombined evidence showed that alcohol consumption is associated with telomere length. The consistent quantifications of alcohol consumption and telomere length would benefit the future aggregation of the evidence from different studies.

cancer biology↗

bioRxiv2018

Identification and quantification of Lyme pathogen strains by deep sequencing of outer surface protein C (ospC) amplicons

Mixed infection of a single tick or host by Lyme disease spirochetes is common and a unique challenge for diagnosis, treatment, and surveillance of Lyme disease. Here we describe a novel protocol for differentiating Lyme strains based on deep sequencing of the hypervariable outer-surface protein C locus (ospC). Improving upon the traditional DNA-DNA hybridization method, the next-generation sequencing-based protocol is high-throughput, quantitative, and able to detect new pathogen strains. We applied the method to over one hundred infected Ixodes scapularis ticks collected from New York State, USA in 2015 and 2016. Analysis of strain distributions within individual ticks suggests an overabundance of multiple infections by five or more strains, inhibitory interactions among co-infecting strains, and presence of a new strain closely related to Borreliella bissettiae. A supporting bioinformatics pipeline has been developed. With the newly designed pair of universal ospC primers targeting intergenic sequences conserved among all known Lyme pathogens, the protocol could be used for culture-free identification and quantification of Lyme pathogens in wildlife and clinical specimens across the globe.

microbiology↗

bioRxiv2018

Detecting Differential Variable microRNAs via Model-Based Clustering

Identifying genomic probes (e.g., DNA methylation marks) is becoming a new approach to detect novel genomic risk factors for complex human diseases. The F test is the standard equal-variance test in Statistics. For high-throughput genomic data, the probe-wise F test has been successfully used to detect biologically relevant DNA methylation marks that have different variances between two groups of subjects (e.g., cases vs. controls). In addition to DNA methylation, microRNA is another mechanism of epigenetics. However, to the best of our knowledge, no studies have identified differentially variable (DV) microRNAs. In this article, we proposed a novel model-based clustering to improve the power of the probe-wise F test to detect DV microRNAs. We imposed special structures on covariance matrices for each cluster of microRNAs based on the prior information about the relationship between variance in cases and variance in controls and about the independence among cases and controls. To the best of our knowledge, the proposed method is the first clustering algorithm that aims to detect DV genomic probes. Simulation studies showed that the proposed method outperformed the probe-wise F test and had certain robustness to the violation of the normality assumption. Based on two real datasets about human hepatocellular carcinoma (HCC), we identified 7 DV-only microRNAs (hsa-miR-1826, hsa-miR-191, hsa-miR-194-star, hsa-miR-222, hsa-miR-502-3p, hsa-miR-93, and hsa-miR-99b) using the proposed method, one (hsa-miR-1826) of which has not yet been reported to relate to HCC in the literature.

bioinformatics↗

bioRxiv2018

Phylogeny Recapitulates Learning: Self-Optimization of Genetic Code

Learning algorithms have been proposed as a non-selective mechanism capable of creating complex adaptive systems in life. Evolutionary learning however has not been demonstrated to be a plausible cause for the origin of a specific molecular system. Here we show that genetic codes as optimal as the Standard Genetic Code (SGC) emerge readily by following a molecular analog of the Hebbs rule (\"neurons fire together, wire together\"). Specifically, error-minimizing genetic codes are obtained by maximizing the number of physio-chemically similar amino acids assigned to evolutionarily similar codons. Formulating genetic code as a Traveling Salesman Problem (TSP) with amino acids as \"cities\" and codons as \"tour positions\" and implemented with a Hopfield neural network, the unsupervised learning algorithm efficiently finds an abundance of genetic codes that are more error-minimizing than SGC. Drawing evidence from molecular phylogenies of contemporary tRNAs and aminoacyl-tRNA synthetases, we show that co-diversification between gene sequences and gene functions, which cumulatively captures functional differences with sequence differences and creates a genomic \"memory\" of the living environment, provides the biological basis for the Hebbian learning algorithm. Like the Hebbs rule, the locally acting phylogenetic learning rule, which may simply be stated as increasing phylogenetic divergence for increasing functional difference, could lead to complex and robust life systems. Natural selection, while essential for maintaining gene function, is not necessary to act at system levels. For molecular systems that are self-organizing through phylogenetic learning, the TSP model and its Hopfield network solution offer a promising framework for simulating emerging behavior, forecasting evolutionary trajectories, and designing optimal synthetic systems.

evolutionary biology↗

bioRxiv2017

The preprophase band-associated kinesin-14 OsKCH2 is a processive minus-end-directed microtubule motor

In animals and fungi, cytoplasmic dynein is a processive motor that plays dominant roles in various intracellular processes. In contrast, land plants lack cytoplasmic dynein but contain many minus-end-directed kinesin-14s. No plant kinesin-14 is known to produce processive motility as a homodimer. OsKCH2 is a plant-specific kinesin-14 with an N-terminal actin-binding domain and a central motor domain flanked by two predicted coiled-coils (CC1 and CC2). Here, we show that OsKCH2 specifically decorates preprophase band microtubules in vivo and transports actin filaments along microtubules in vitro. Importantly, OsKCH2 exhibits processive minus-end-directed motility on single microtubules as individual homodimers. We find that CC1 but not CC2 forms the coiled-coil for OsKCH2 dimerization. Instead, CC2 functions to enable OsKCH2 processivity by enhancing its binding to microtubules. Collectively, these results show that land plants have evolved unconventional kinesin-14 homodimers with inherent minus-end-directed processivity that may function to compensate for the loss of cytoplasmic dynein.

biophysics↗

bioRxiv2016

A SUMO-Ubiquitin Relay Recruits Proteasomes to Chromosome Axes to Regulate Meiotic Recombination

Meiosis produces haploid gametes through a succession of chromosomal events including pairing, synapsis and recombination. Mechanisms that orchestrate these events remain poorly understood. We found that the SUMO-modification and ubiquitin-proteasomes systems regulate the major events of meiotic prophase in mouse. Interdependent localization of SUMO, ubiquitin and proteasomes along chromosome axes was mediated largely by RNF212 and HEI10, two E3 ligases that are also essential for crossover recombination. RNF212-dependent SUMO conjugation effected a checkpoint-like process that stalls recombination by rendering the turnover of a subset of recombination factors dependent on HEI10-mediated ubiquitylation. We propose that SUMO conjugation establishes a precondition for designating crossover sites via selective protein stabilization. Thus, meiotic chromosome axes are hubs for regulated proteolysis via SUMO-dependent control of the ubiquitin-proteasome system.\n\nOne Sentence SummaryChromosomal events of meiotic prophase in mouse are regulated by proteasome-dependent protein degradation.

genetics↗