Biology subjects

Chen, D.

Publications and source records attributed to Chen, D..

At least 397 records · Page 22Linked to original sources

bioRxiv2019

Precise annotation of human, chimpanzee, rhesus macaque and mouse mitochondrial genomes using 5’ and 3’ end small RNAs

Using 5 and 3 end small RNAs, we annotated human, chimpanzee, rhesus macaque and mouse mitochondrial genomes at 1 base-pair (bp) resolution to cover both strands of the mammalian mitochondrial genome entirely without leaving any gaps or overlaps. The precise annotation of all coding and non-coding genes (e.g. ncMT1, MDL2 and MDL1AS) led to the discovery of novel functions and mechanisms of mitochondrion. In this study, we defined the conserved sequence block (CSB) region to span five CSBs (CSB1, CSB2, CSB3, LSP and HSP) and identified the motifs of five CSBs in the mitochondrial displacement loop (D-loop) regions of 52 mammals. The conserved arrangement of these five CSBs in 17 primates inspired us to investigate the function of the mtDNA D-loop, which has been puzzling scientists for more than 50 years. We found that 5 sRNAs of MDL1AS control the expression levels of mitochondrial genes as a whole by a negative feedback mechanism. Thus, the precise annotations of three CSBs (CSB2, LSP and HSP) in more species will help to understand the function of the mtDNA D-loop. The precision annotation of animal mitochondrial genomes also provides abundant information for studying the molecular phylogenetics and evolution of animals.

bioinformatics↗

bioRxiv2019

MethylNet: A Modular Deep Learning Approach to Methylation Prediction

BackgroundDNA methylation (DNAm) is an epigenetic regulator of gene expression programs that can be altered by environmental exposures, aging, and in pathogenesis. Traditional analyses that associate DNAm alterations with phenotypes suffer from multiple hypothesis testing and multi-collinearity due to the high-dimensional, continuous, interacting and non-linear nature of the data. Deep learning analyses have shown much promise to study disease heterogeneity. DNAm deep learning approaches have not yet been formalized into user-friendly frameworks for execution, training, and interpreting models. Here, we describe MethylNet, a DNAm deep learning method that can construct embeddings, make predictions, generate new data, and uncover unknown heterogeneity with minimal user supervision. ResultsThe results of our experiments indicate that MethylNet can study cellular differences, grasp higher order information of cancer sub-types, estimate age and capture factors associated with smoking in concordance with known differences. ConclusionThe ability of MethylNet to capture nonlinear interactions presents an opportunity for further study of unknown disease, cellular heterogeneity and aging processes.

bioinformatics↗

bioRxiv2019

β-blockers augment L-type Ca2+ channel activity by target-selective spatially restricted β2AR-cAMP-PKA signaling in neurons

G protein-coupled receptors (GPCRs) transduce pleiotropic intracellular signals in mammalian cells. Here, we report that some antagonists of {beta} adrenergic receptors ({beta}ARs) such as {beta}-blocker carvedilol and alprenolol activate {beta}2AR at nanomolar concentrations, which promote G protein signaling and cAMP/PKA activity without action of G protein receptor kinases (GRKs). The cAMP/PKA signal is restricted within the local plasma membrane domain, leading to selectively enhance PKA-dependent augment of endogenous L-type calcium channel (LTCC) activity but not AMPA receptor in hippocampal neurons. Moreover, we have engineered a mutant {beta}2AR that lacks serine 204 and 207 in the catecholamine binding pocket. This mutant can be preferentially activated by carvedilol but not the orthosteric agonist isoproterenol. Carvedilol activates the mutant {beta}2AR in hippocampal neurons augmenting LTCC activity through cAMP/PKA signaling. Together, our study identifies a mechanism by which {beta}-blocker-dependent activation of GPCRs at low ligand concentrations promotes local cAMP/PKA signaling to selectively target membrane downstream effectors such as LTCC in neurons.

cell biology↗

bioRxiv2019

Inhibition of Histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing

Despite the rapid development of CRISPR/Cas9-mediated gene editing technology, the gene editing potential of CRISPR/Cas9 is hampered by low efficiency, especially for clinical applications. One of the major challenges is that chromatin compaction inevitably limits the Cas9 protein access to the target DNA. However, chromatin compaction is precisely regulated by histone acetylation and deacetylation. To overcome these challenges, we have comprehensively assessed the impacts of histone modifiers such as HDAC (1-9) inhibitors and HAT (p300/CBP, Tip60 and MOZ) inhibitors, on CRISPR/Cas9 mediated gene editing efficiency. Our findings demonstrate that attenuation of HDAC1, HDAC2 activity, but not other HDACs, enhances CRISPR/Cas9-mediated gene knockout frequencies by NHEJ as well as gene knock-in by HDR. Conversely, inhibition of HDAC3 decreases gene editing frequencies. Furthermore, our study showed that attenuation of HDAC1, HDAC2 activity leads to an open chromatin state, facilitates Cas9 access and binding to the targeted DNA and increases the gene editing frequencies. This approach can be applied to other nucleases, such as ZFN and TALEN.

genomics↗

bioRxiv2019

Genome-wide identification of long non-coding RNAs and their regulatory networks involved in Apis mellifera ligustica response to Nosema ceranae infection

Long non-coding RNAs (lncRNAs) are a diverse class of transcripts that structurally resemble mRNAs but do not encode proteins, and lncRNAs have been proved to play pivotal roles in a wide range of biological processes in animals and plants. However, knowledge of expression pattern and potential role of honeybee lncRNAs response to Nosema ceranae infection is completely unknown. Here, we performed whole transcriptome strand-specific RNA sequencing of normal midguts of Apis mellifera ligustica workers (Am7CK, Am10CK) and N. ceranae-inoculated midguts (Am7T, Am10T), followed by comprehensive analyses using bioinformatic and molecular approaches. A total of 6353 A. m. ligustica lncRNAs were identified, including 4749 conserved lncRNAs and 1604 novel lncRNAs. These lncRNAs had low sequence similarities with other known lncRNAs in other species; however, their structural features were similar with counterparts in mammals and plants, including shorter exon and intron length, lower exon number, and lower expression level, compared with protein-coding transcripts. Further, 111 and 146 N. ceranae-responsive lncRNAs were identified from midguts at 7 day post inoculation (dpi) and 10 dpi compared with control midguts. 12 differentially expressed lncRNAs (DElncRNAs) were shared by Am7CK vs Am7T and Am10CK vs Am10T comparison groups, while the numbers of unique ones were 99 and 134, respectively. Functional annotation and pathway analysis showed the DElncRNAs may regulate the expression of neighboring genes by acting in cis. Moreover, we discovered 27 lncRNAs harboring eight known miRNA precursors and 513 lncRNAs harboring 2257 novel miRNA precursors. Additionally, hundreds of DElncRNAs and their target miRNAs were found to form complex competitive endogenous RNA (ceRNA) networks, suggesting these DElncRNAs may act as miRNA sponges. Furthermore, DElncRNA-miRNA-mRNA networks were constructed and investigated, the result demonstrated that part of DElncRNAs were likely to participate in regulating the material and energy metabolism as well as cellular and humoral immune during host responses to N. ceranae invasion. Finally, the expression pattern of 10 DElncRNAs was validated using RT-qPCR, confirming the reliability of our sequencing data. Our findings revealed here offer not only a rich genetic resource for further investigation of the functional roles of lncRNAs involved in A. m. ligustica response to N. ceranae infection, but also a novel insight into understanding host-pathogen interaction during microsporidiosis of honeybee.

bioinformatics↗

bioRxiv2019

A Clostridia-rich microbiota contributes to increased excretion of bile acids in diarrhea-predominant irritable bowel syndrome

ObjectiveAn excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remains unclear. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D.\n\nDesignMetabolomic and metagenomic analyses were performed of specimens from 290 IBS-D patients and 89 healthy volunteers. By transplanting human microbiota and manipulating specific microbiome species in mice, the effects of microbiota on host BA metabolism were assessed at metabolic, genetic and protein levels. Effects of individual and mixed BAs on enterohepatic feedback pathways were also tested in vitro and in vivo.\n\nResultsTotal fecal BAs were excessively excreted in 24.5% of IBS-D patients. Their fecal metagenomes showed increased abundances of Clostridia and BA-transforming genes (hdhA and bais). The increases of Clostridia bacteria (e.g. C. scindens) were positively associated with the levels of fecal BAs and serum 7-hydroxy-4-cholesten-3-one (C4), while being negatively correlated with serum fibroblast growth factor 19 (FGF19). Both Clostridia-rich human microbiota and C. scindens enhanced levels of serum C4 and hepatic conjugated BAs in mice recipients and reduced ileal FGF19 expression. Inhibition of Clostridium species by vancomycin yielded opposite findings. Clostridia-derived BAs (e.g. conjugated and free ursodeoxycholic acid) significantly suppressed intestinal FGF19 expression.\n\nConclusionThe Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients. This study provided the basis for more precise clinical diagnosis and management for IBS-D.

microbiology↗

bioRxiv2019

Soil and vegetation conditions changes following the different sand dune restoration measures on the Zoige Plateau

Restoration of alpine sand dunes has been increasingly attracting the attention of ecologists due to their difficulty and importance among the mountain-river-forest-farmland-lake-grass system (referred as meta-ecosystem) restoration. Alpine sand dunes are suffered from unstable soil and lack of plants. Efficient restoration measures are vital to guide the sand dune restoration. Whether the engineering materials co-applied with seeding could achieve considerable restoration in such areas? Here, sandbag and wicker as environmental friendly materials combined with Elymus nutans seeding were implemented on the Zoige Plateau sand dune, comparing with the control treatment that only seeding. We assessed the topsoil conditions by sampled the surface soil and measured the water capacity and nutrients. We also utilized interspecific relationship and population niche to analyse the plant community structure variances among different restoration measures. Results showed that the soil conditions got clearly improved in sandbag area than that in wicker area when compared with that in control area. The community in control area was the least structured, while the species showed the closest related in sandbag area. In addition, average population niche overlap showed a control (0.26) < wicker (0.32) < sandbag (0.39) ranking. Thus, we suggested that sandbag or wicker co-applied with indigenous grass seeding is a practical and quick restoration approach in alpine sand dunes, and the sandbag may surpasses the wicker. Moreover, soil amending measures including nutrient improvement, and microbial fertilizer addition may further accelerate sand dune restoration.

ecology↗

bioRxiv2019

Sing cell RNA-seq reveals cellular diversity and developmental characteristics of human infant retina

Retina, located in the innermost layer of the eye of human, holds the decisive role in visual perception. Dissecting the heterogeneity of retina is essential for understanding the mechanism of vision formation and even the development of central nervous system (CNS). Here, we performed single cell RNA-seq, analyzed 57,832 cells from human infant donors, resulting in 20 distinct clusters representing major cell types in retina: rod photoreceptors, cone photoreceptors, bipolar cells, horizontal cells, amacrine cells, Muller glia cells and microglia. We next constructed extensive networks of intercellular communication and identified ligand-receptor interactions playing crucial roles in regulating neural cell development and immune homeostasis in retina. Though re-clustering, we identified known subtypes in cone PRs and additional unreported subpopulations and corresponding markers in rod PRs as well as bipolar cells. Additionally, we linked inherited retinal disease to certain cell subtypes or subpopulations through enrichment analysis. Intriguingly, we found that status and functions of photoreceptors changed drastically between early and late retina. Overall, our study offers the first retinal cell atlas in human infants, dissecting the heterogeneity of retina and identifying the key molecules in the developmental process, which provides an important resource that will pave the way for retina development mechanism research and regenerative medicine concerning retinal biology.

cell biology↗

bioRxiv2019

Single cell RNA sequencing reveals cellular diversity of trisomy 21 retina

Retina is a crucial tissue for the capturing and processing of light stimulus. Characterization of the retina at single cell level is essential for the understanding of its biological functions. A variety of abnormalities in terms of morphology and function were reported in T21 retina. To evaluate the effects of chromosome aneuploidy on retina development, we characterized single cell transcriptional profiles of a T21 fetus and performed comprehensive bioinformatic analyses. Our data revealed the diversity and heterogeneity of cellular compositions in T21 retina. In total, we identified seven major cell types, and detected several subtypes within each cell type, followed by the detection of corresponding molecular markers including previously reported ones and a series of novel markers. Our analyses identified extensive communication networks between distinct cellular types, among which a few ligand-receptor interactions were associated with the development of retina and immunoregulatory interactions. Taken together, our data provided the first single cell transcriptome profile for human T21 retina which facilitates our understanding on the dosage effects of chromosome 21 on the development of retina.

cell biology↗

bioRxiv2019

Pan-genome analysis reveals the molecular basis of niche adaptation of Staphylococcus epidermidis strains

Staphylococcus epidermidis is the most commonly isolated species from human skin and the second leading cause of bloodstream infections. Here, we performed a large-scale comparative study without any pre-assigned reference to identify genomic determinants associated with their diversity and adaptation as a \"double-side spy\", a skin dominant colonization, and a successful pathogen. The pan-genome of S. epidermidis is open with 435 core proteins and a pan-genome size of 8034 proteins. Genome-wide phylogenetic tree shows that whole genome sequence is a powerful tool to analyze the complex evolutionary process of S. epidermidis and investigate the source of infection. Comparative genome analyses demonstrate the high diversity of antimicrobial resistances, especially mobile genetic elements. The complicated relationships of host-bacterium and bacterium-bacterium help S. epidermidis to play a vital role in balancing the epithelial microflora. The highly variable and dynamic nature of the S. epidermidis genome may be the result of its success in adapting to broad habitats, which is necessary to deal with complex environments. This study gives the general landscape of S. epidermidis pan-genome and provides valuable insights into mechanisms for genome evolution and lifestyle adaptation of this ecologically flexible species.

microbiology↗

bioRxiv2019

Demographic histories and genome-wide patterns of divergence in incipient species of shorebirds

Understanding how incipient species are maintained with gene flow is a fundamental question in evolutionary biology. Whole genome sequencing of multiple individuals holds great potential to illustrate patterns of genomic differentiation as well as the associated evolutionary histories. Kentish (Charadrius alexandrinus) and the white-faced (C. dealbatus) plovers, which differ in their phenotype, ecology and behaviour, are two incipient species and parapatrically distributed in East Asia. Previous studies show evidence of genetic diversification with gene flow between the two plovers. Under this scenario, it is of great importance to explore the patterns of divergence at the genomic level and to determine whether specific regions are involved in reproductive isolation and local adaptation. Here we present the first population genomic analysis of the two incipient species based on the de novo Kentish plover reference genome and resequenced populations. We show that the two plover lineages are distinct in both nuclear and mitochondrial genomes. Using model-based coalescence analysis, we found that population sizes of Kentish plover increased whereas white-faced plovers declined during the Last Glaciation Period. Moreover, the two plovers diverged allopatrically, with gene flow occurring after secondary contact. This has resulted in low levels of genome-wide differentiation, although we found evidence of a few highly differentiated genomic regions in both the autosomes and the Z-chromosome. This study illustrates that incipient shorebird species with gene flow after secondary contact can exhibit discrete divergence at specific genomic regions and provides basis to further exploration on the genetic basis of relevant phenotypic traits.

evolutionary biology↗

bioRxiv2019

Systematic identification of circular RNAs and corresponding regulatory networks unveil their potential roles in the midgut of Apis cerana cerana workers

BackgroundCircular RNAs (circRNAs) are newly discovered noncoding RNAs (ncRNAs) that play key roles in various biological functions, such as the regulation of gene expression and alternative splicing. CircRNAs have been identified in some species, including western honeybees. However, the understanding of honeybee circRNA is still very limited, and to date, no study on eastern honeybee circRNA has been conducted. Here, the circRNAs in the midguts of Apis cerana cerana workers were identified and validated, and the regulatory networks were constructed. Differentially expressed circRNAs (DEcircRNAs) and the corresponding competitively endogenous RNA (ceRNA) networks in the development of the workers midgut were further investigated. ResultsHere, 7- and 10-day-old A. c. cerana workers midguts (Ac1 and Ac2) were sequenced using RNA-seq, and a total of 9589 circRNAs were predicted using bioinformatics. These circRNAs were approximately 201-800 nt in length and could be classified into six types; the annotated exonic circRNAs were the most abundant. Additionally, five novel A. c. cerana circRNAs were confirmed by PCR amplification and Sanger sequencing, indicating the authenticity of A. c. cerana circRNAs. Interestingly, novel_circ_003723, novel_circ_002714, novel_circ_002451 and novel_circ_001980 were the most highly expressed circRNAs in both Ac1 and Ac2, which is indicative of their key roles in the development of the midgut. Moreover, 55 DEcircRNAs were identified in the Ac1 vs Ac2 comparison group, including 34 upregulated and 21 downregulated circRNAs. Further investigation showed that the source genes of circRNAs were classified into 34 GO terms and were involved in 141 KEGG pathways. In addition, the source genes of DEcircRNAs were categorized into 10 GO terms and 15 KEGG pathways, which demonstrated that the corresponding DEcircRNAs may affect the growth, development, and material and energy metabolisms of the workers midgut by regulating the expression of the related source genes. Additionally, the circRNA-miRNA regulatory networks were constructed and analyzed, and the results demonstrated that 1060 circRNAs can bind to 74 miRNAs and that 71.51% of circRNAs can be linked to only one miRNA. Furthermore, the DEcircRNA-miRNA-mRNA networks were constructed and explored, and the results indicate that the 13 downregulated circRNAs can bind to eight miRNAs and to 29 target genes. In addition, the results indicate that the 16 upregulated circRNAs can bind to 9 miRNAs and to 29 target genes, demonstrating that DEcircRNAs are likely involved in the regulation of midgut development via ceRNA mechanisms. Moreover, the regulatory networks of miR-6001-y-targeted DEcircRNAs were analyzed, and the results showed that eight DEcircRNAs may affect the development of A. c. cerana workers midguts by targeting miR-6001-y. Finally, four randomly selected DEcircRNAs were verified via RT-qPCR, confirming the reliability of our sequencing data. ConclusionThis is the first systematic investigation of circRNAs and their corresponding regulatory networks in eastern honeybees. The identified circRNAs from the A. c. cerana workers midgut will enrich the known reservoir of honeybee ncRNAs. DEcircRNAs may play a comprehensive role during the development of the workers midgut via the regulation of source genes and the interaction with miRNAs by acting as ceRNAs. The eight DEcircRNAs that targeted miR-6001-y were likely to be vital for the development of the workers midgut. Our results provide a valuable resource for the future studies of A. c. cerana circRNA and lay a foundation to reveal the molecular mechanisms underlying the regulatory networks of circRNAs responsible for the workers midgut development; in addition, these findings facilitate a functional study on the key circRNAs involved in the developmental process. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

molecular biology↗

bioRxiv2019

Analysis of synapse-level neuronal morphology in human post-mortem brain tissue

Many cognitive and psychiatric disorders are thought to be disorders of the synapse, yet the precise synapse defects underlying these disorders remain unknown. Because synapses are highly specialized anatomical structures, defects in synapse formation and function can often be observed as changes in micro-scale neuroanatomy. Unfortunately, few methods are available for accurate analysis of synapses in human post-mortem tissues. Here, we present a new methodological pipeline for assessing synapse-level neuron morphology in human post-mortem tissue that is accurate, rapid, and relatively inexpensive. Our method uses small tissue blocks from postmortem human brains, immersion fixation, single cell resolution by dye labeling, and confocal microscopy. As proof of principle, we analyzed pre-and postsynaptic structures from hippocampi of 13 individuals aged 4 months to 71 years. Our results suggest that postsynaptic CA1 dendritic spine shape and density are stable across ages, while presynaptic DG mossy fiber boutons undergo significant structural rearrangements with normal aging. This suggests that mossy fiber synapses, which play a major role in learning and memory, remain dynamic throughout life. Importantly, we find no effect of postmortem intervals up to 28 hours on neuron morphology. Thus, the ease of our new protocol should facilitate higher powered studies of human synapse structure in healthy and diseased states.

neuroscience↗

bioRxiv2019

Haplotype-Based Noninvasive Prenatal Diagnosis for Duchenne Muscular Dystrophy: A pilot study in South China

ObjectiveTo explore the accuracy and feasibility of noninvasive prenatal diagnosis (NIPD) for Duchenne Muscular Dystrophy (DMD) based on the haplotype approach. MethodsWe recruited singleton pregnancies at-risk of DMD at 12-25 weeks of gestation from 17 families who all had a proband children affected by DMD. We have identified the pathogenic mutations in probands and their mothers by multiplex ligation-dependent probe amplification (MLPA). To construct parental haplotypes, we performed captured sequencing on genomic DNA from parents and probands. The integration analysis of parental haplotypes and targeted sequencing results of maternal plasma DNA were used to infer the fetal haplotype and genotypes in DMD gene. Fetal DMD genotypes were further confirmed by invasive prenatal diagnosis. ResultsWe have successfully performed the haplotype-based NIPD in all recruited families. Ten fetuses were identified as normal, including four female and six male fetuses. Four female fetuses were carriers and the other three male fetuses were affected by DMD with exons 49-52 deletion, exons 8-37 deletion and c.628G > T mutation, respectively. The results of NIPD were consistent with those of invasive diagnosis. ConclusionHaplotype-based NIPD for DMD by targeted sequencing is promising and has potential for clinical application.

genetics↗

bioRxiv2019

Comparative study of GenePOC GBS LB Assay and GeneXpert GBS LB Assay for the detection of Group B Streptococcus in prenatal screening samples.

Group B Streptococcal (GBS) infections in the United States are a leading cause of meningitis and sepsis in newborns. The CDC, therefore recommends GBS screening for all pregnant women at 35-37 weeks of gestation and administration of intrapartum prophylaxis (in those that tested positive) as an effective means of controlling disease transmission. Several FDA approved molecular diagnostic tests are available for rapid and accurate detection of GBS in antepartum women. In this study, we report a clinical comparison of the Xpert GBS LB assay and a novel FDA-cleared test, GenePOC GBS LB assay. A total of 250 vaginal-rectal swabs from women undergoing prenatal screening were submitted to the University of Wisconsins clinical microbiology laboratory for GBS testing. We found 96.8% of samples were concordant between the two tests, while 3.2% were discordant with higher sensitivity observed for the GenePOC GBS LB assay, and higher specificity for the GeneXpert GBS LB assay.

microbiology↗

bioRxiv2019

Translational regulation of non-autonomous mitochondrial stress response promotes longevity

Inhibition of mRNA translation delays aging, but the underlying mechanisms remain underexplored. Mutations in both DAF-2 (IGF-1 receptor) and RSKS-1 (ribosomal S6 kinase/S6K) cause synergistic lifespan extension in C. elegans. To understand the roles of S6K-mediated translational regulation in this process, we performed genome-wide translational profiling and genetic screens to identify genes that are not only regulated at the translational level in the daf-2 rsks-1 mutant, but also affect lifespan. Inhibition of CYC-2.1 (cytochrome c) in the germline significantly extends lifespan through non-autonomous activation of the mitochondrial unfolded protein response (UPRmt) and AMP-activated kinase (AMPK) in the metabolic tissue. Furthermore, the RNA-binding protein GLD-1-mediated translational repression of cytochrome c in the germline is important for the non-autonomous activation of UPRmt and synergistic longevity of the daf-2 rsks-1 mutant. Together, these results illustrate a translationally regulated non-autonomous mitochondrial stress response mechanism in the modulation of lifespan by insulin-like signaling and S6K. HighlightsO_LILongevity of the daf-2 rsks-1 mutant is mediated by translational repression of ribosomal proteins and CYC-2.1/cytochrome c. C_LIO_LIGermline inhibition of cyc-2.1 non-autonomously activates UPRmt and AMPK to extend lifespan. C_LIO_LIGLD-1 represses germline cyc-2.1 translation in the daf-2 rsks-1 mutant. C_LIO_LITranslational regulation of cyc-2.1 and UPRmt contribute to the synergistic longevity of the daf-2 rsks-1 mutant. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/533695v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@9f3ce7org.highwire.dtl.DTLVardef@576930org.highwire.dtl.DTLVardef@bb0c09org.highwire.dtl.DTLVardef@133ce4_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2019

Association between ApoE polymorphism and type 2 diabetes: A meta-analysis of 59 studies

(1) AimsDue to the ever increasing incidence of T2DM, it is estimated that only half of the 79 million adults with type 2 diabetes (T2DM) will have adequate access to insulin by 2030 if the current levels of access is not improved. It is urgent to identify the important risk factors for T2DM and develop effective strategies to address the problem of T2DM. Our study aimed to evaluate the association between apolipoprotein E (ApoE) genetic polymorphism and type 2 diabetes, and to provide clues for the etiology of T2DM and even molecular marker of targeted therapy for the treatment of T2DM. (2) MethodsCase-control studies of ApoE polymorphism and T2DM, which were included in PubMed, Web of Science, Medline, WanFang, VIP, and CNKI databases, were selected and evaluated according to criteria of inclusion and exclusion. Eligible data were extracted and pooled, and were analyzed and assessed using R soft-ware (version 3.4.3). Random-effect models were used when heterogeneity existed in between-study, and fixed-effect models were applied otherwise. (3) ResultsA total of 59 studies that consisted of 6,872 cases with T2DM and 8,250 controls were selected. Alleles and genotypes of ApoE between cases and controls were compared. For ApoE alleles, we observed the contrast of {varepsilon}4 versus {varepsilon}3 allele yielding a pooled OR of 1.18 (95% CI: 1.09-1.28; P<0.001). For ApoE genotypes, compared with {varepsilon}3/{varepsilon}3 genotype, {varepsilon}2/{varepsilon}2 genotype showed a possible association with T2DM (OR=1.46; 95% CI: 1.11-1.93; P=0.007), {varepsilon}3/{varepsilon}4 genotype had a 1.11-fold risk of developing T2DM (OR=1.11; 95% CI: 1.01-1.22; P=0.039), and {varepsilon}4/{varepsilon}4 genotype had a 1.71-fold risk of developing T2DM (OR=1.71; 95% CI: 1.33-2.19; P<0.001). (4) ConclusionsThere is an association between ApoE polymorphism and T2DM: allele {varepsilon}4 and genotypes ({varepsilon}2/{varepsilon}2, {varepsilon}3/{varepsilon}4, and {varepsilon}4/{varepsilon}4) are associated with the increased risk for the development of T2DM, and they may be risk factors for T2DM.

genetics↗

bioRxiv2019

FabriEVEs: A dedicated platform for endogenous viral elements in fishes, amphibians, birds, reptiles and invertebrates

Endogenous viral elements (EVEs) are heritable viral deriving elements present in the genomes of other species. As DNA fossils left by ancient viruses, EVEs were used to infer the characteristics of extinct viruses. EVEs in mammals have been well classified by several databases, however, EVEs in non-mammalian organisms are poorly documented. Here, we report FabriEVEs (http://tfbsbank.co.uk/FabriEVEs), the first dedicated and comprehensive online platform for the collection, classification and annotation of EVEs in fishes, amphibians, birds, reptiles and invertebrates. In total, nearly 1.5 million EVEs from 82 species deriving from class I (dsDNA), II (ssDNA), III (dsRNA), IV (positive ssRNA), V (negative ssRNA), VI (ssRNA-RT) and VII (dsDNA-RT) viruses were recorded in FabriEVEs, accompanying with comprehensive annotation including the species name, location, genomic features, virus family and associated literature. Flexible and powerful query options were provided to pinpoint desired EVEs. Furthermore, FabriEVEs provides free access to all EVEs data in case users need to download them for further analysis. Taken together, our database provided systematic classification and annotation of EVEs in non-mammal species, which paves the way for comparative analysis of EVEs and throws light upon the co-evolution of EVEs and their hosts.

evolutionary biology↗