SEARCH · Search bioRxiv

Results for “Bioinformatics”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources

bioRxiv2018

Compound heterozygous ZP1 mutations cause empty follicle syndrome in infertile sisters

PurposeEmpty follicle syndrome (EFS) is a condition in which no oocyte is retrieved from mature follicles after proper ovarian stimulation in an in vitro fertilization (IVF) procedure. Genetic evidence accumulates for the etiology of recurrent EFS even with improved medical treatment which had avoided the pharmacological or iatrogenic problems. Here, this study investigated the genetic cause of recurrent EFS in a family with two infertile sisters.\n\nMethodsIn this work, we present two infertile sisters in a family with recurrent EFS after three cycles of standard ovarian stimulation with hCG and/or GnRHa therapy. We performed whole-exome sequencing and targeted sequencing in the core members of this family, and further bioinformatics analysis to identify pathogenesis of gene.\n\nResultsWe identified compound heterozygous variants, c.161_165del (p.54fs) and c.1166_1173del (p.389fs), on zona pellucida glycoprotein 1 (ZP1) gene, which were shared with two infertile sisters. Cosegregation tests on the affected and unaffected members of this family confirmed that the allelic mutants were transmitted from either parent.\n\nConclusionsThis EFS phenotype was distinct from the previously reported disruption of zona pellucida due to homozygous ZP1 defects. We thus propose that the specific mutations in ZP1 gene may render a causality for the recurrent EFS.

genetics↗

bioRxiv2018

Alzheimer’s disease risk SNPs show no strong effect on miRNA expression in human lymphoblastoid cell lines

The role of microRNAs (miRNAs) in the pathogenesis of Alzheimers disease (AD) is currently extensively investigated. In this study, we assessed the potential impact of AD genetic risk variants on miRNA expression by performing large-scale bioinformatic data integration. Our analysis was based on genetic variants from three AD genome-wide association studies (GWAS). Association with miRNA expression was tested by expression quantitative trait loci (eQTL) analysis using next-generation miRNA sequencing data generated in lymphoblastoid cell lines (LCL). While, overall, we did not identify a strong effect of AD GWAS variants on miRNA expression in this cell type we highlight two notable outliers, i.e. miR-29c-5p and miR-6840-5p. MiR-29c-5p was recently reported to be involved in the regulation of BACE1 and SORL1 expression. In conclusion, despite two exceptions our large-scale assessment provides only limited support for the hypothesis that AD GWAS variants act as miRNA eQTLs.

genetics↗

bioRxiv2018

Lmx1a drives Cux2 expression in the cortical hem through activation of a conserved intronic enhancer.

During neocortical development, neurons are produced by a diverse pool of neural progenitors. A subset of progenitors express the Cux2 gene and are fate-restricted to produce certain neuronal subtypes, but the upstream pathways that specify these progenitor fates remain unknown. To uncover the transcriptional networks that regulate Cux2 expression in the forebrain, we characterized a conserved Cux2 enhancer that we find recapitulates Cux2 expression specifically in the cortical hem. Using a bioinformatic approach, we found several potential transcription factor (TF) binding sites for cortical hem-patterning TFs. We found that the homeobox transcription factor, Lmx1a, can activate the Cux2 enhancer in vitro. Furthermore, we show that multiple Lmx1a binding sites required for enhancer activity in the cortical hem in vivo. Mis-expression of Lmx1a in neocortical progenitors caused an increase in Cux2+-lineage cells. Finally, we compared several conserved human enhancers with cortical hem-restricted activity and found that recurrent Lmx1a binding sites are a top shared feature. Uncovering the network of TFs involved in regulating Cux2 expression will increase our understanding of the mechanisms pivotal in establishing Cux2-lineage fates in the developing forebrain.\n\nSummary StatementAnalysis of a cortical hem-specific Cux2 enhancer reveals role for Lmx1a as a critical upstream regulator of Cux2 expression patterns in neural progenitors during early forebrain development.

neuroscience↗

bioRxiv2018

Identification of novel RNA viruses associated to bird’s-foot trefoil (Lotus corniculatus)

Birds-foot trefoil (Lotus corniculatus) is a nutritious forage crop, employed for livestock foraging around the world. Here, we report the identification and characterization of two novel viruses associated with birds-foot trefoil. Virus sequences with affinity to enamoviruses (ssRNA (+); Luteoviridae; Enamovirus) and nucleorhabdoviruses (ssRNA (-); Rhabdoviridae; Nucleorhabdovirus) were detected in L. corniculatus transcriptome data. The tentatively named birds-foot trefoil associated virus 1 (BFTV-1) genome organization is characterized by 13,626 nt long negative-sense ssRNA. BFTV-1 presents in its antigenome orientation six predicted gene products in the canonical order 3'-N-P-P3-M-G-L-5'. The proposed birds-foot trefoil associated virus 2 (BFTV-2) 5,736 nt virus sequence presents a typical 5'-PO-P1-2-IGS-P3-P5-3' enamovirus genome structure. Phylogenetic analysis suggests that BFTV-1 is closely related to Datura yellow vein nucleorhabdovirus, and that BFTV-2 clusters into a monophyletic cluster of legumes-associated enamoviruses. This sub-clade of highly related and co-divergent legume associated viruses provides insights on the evolutionary history of the enamoviruses. The bioinformatic reanalysis of SRA libraries deposited in the NCBI database constitutes an emerging approach to the discovery of novel plant viruses which should be important for both quarantine purposes and disease management.

plant biology↗

bioRxiv2018

The structural complexity of the Gammaproteobacteria flagellar motor is related to the type of its torque-generating stators

The bacterial flagellar motor is a cell-envelope-embedded macromolecular machine that functions as a propeller to move the cell. Rather than being an invariant machine, the flagellar motor exhibits significant variability between species, allowing bacteria to adapt to, and thrive in, a wide range of environments. For instance, different torque-generating stator modules allow motors to operate in conditions with different pH and sodium concentrations and some motors are adapted to drive motility in high-viscosity environments. How such diversity evolved is unknown. Here we use electron cryo-tomography to determine the in situ macromolecular structures of the flagellar motors of three Gammaproteobacteria species: Legionella pneumophila, Pseudomonas aeruginosa, and Shewanella oneidensis MR-1, providing the first views of intact motors with dual stator systems. Complementing our imaging with bioinformatics analysis, we find a correlation between the stator system of the motor and its structural complexity. Motors with a single H+-driven stator system have only the core P- and L-rings in their periplasm; those with dual H+-driven stator systems have an extra component elaborating their P-ring; and motors with Na+- (or dual Na+-H+)- driven stator systems have additional rings surrounding both their P- and L-rings. Our results suggest an evolution of structural complexity that may have enabled pathogenic bacteria like L. pneumophila and P. aeruginosa to colonize higher-viscosity environments in animal hosts.

microbiology↗

bioRxiv2018

The landscape of S100B+ and HLA-DR+ dendritic cell subsets in tonsils at the single cell level via high-parameter mapping

Dendritic cells (DC) (classic, plasmacytoid, inflammatory) are an intense focus of interest because of their role in inflammation, autoimmunity, vaccination and cancer. We present a tissue-based classification of human DC subsets in tonsils with a high-parameter (>40 markers) immunofluorescent approach, cell type-specific image segmentation and the use of bioinformatics platforms. Through this deep phenotypic and spatial examination, classic cDC1, cDC2, pDC subsets have been further refined and a novel subset of DC co-expressing IRF4 and IRF8 identified. Based on unique tissue locations within the tonsil, and close interactions with T cells (cDC1) or B cells (cDC2), DC subsets can be further subdivided by correlative phenotypic changes associated with these interactions. In addition, monocytes and macrophages expressing HLA-DR or S100AB are identified and localized in the tissue. This study thus provides a whole tissue in situ catalog of human DC subsets and their cellular interactions within spatially defined niches.

immunology↗

bioRxiv2018

sigfit: flexible Bayesian inference of mutational signatures

Mutational signature analysis aims to infer the mutational spectra and relative exposures of processes that contribute mutations to genomes. Different models for signature analysis have been developed, mostly based on non-negative matrix factorisation or non-linear optimisation. Here we present sigfit, an R package for mutational signature analysis that applies Bayesian inference to perform fitting and extraction of signatures from mutation data. We compare the performance of sigfit to prominent existing software, and find that it compares favourably. Moreover, sigfit introduces novel probabilistic models that enable more robust, powerful and versatile fitting and extraction of mutational signatures and broader biological patterns. The package also provides user-friendly visualisation routines and is easily integrable with other bioinformatic packages.

cancer biology↗

bioRxiv2018

CRISPR/Cas9 Targeted Capture Of Mammalian Genomic Regions For Characterization By NGS

The robust detection of structural variants in mammalian genomes remains a challenge. It is particularly difficult in the case of genetically unstable Chinese hamster ovary (CHO) cell lines with only draft genome assemblies available. We explore the potential of the CRISPR/Cas9 system for the targeted capture of genomic loci containing integrated vectors in CHO-K1-based cell lines, and compare it to popular target-enrichment methods and to whole genome sequencing (WGS). The CRISPR/Cas9-based techniques allow for amplification-free capture of genomic regions, which reduces the possibility of sequencing artifacts. Other advantages of these methods are the ease of bioinformatics analysis, potential for multiplexing, and the production of longer sequencing templates for real-time sequencing. The utility of these protocols has been proven by identification of transgene integration sites and flanking sequences in a number of CHO cell lines. However, data produced by these and other targeted capture methods are not always sufficient to analyze complex genomic rearrangements (CGRs) or unexpected sequences introduced into genome by vector integration events. In contrast, WGS provides complete information about vector integration sites, vector copy number, CGRs, and foreign DNA-but despite these benefits, WGS is not easily implemented due to the cost and complexity of the analysis.

genomics↗

bioRxiv2018

An open source platform for analyzing and sharing worm behavior data

Animal behavior is increasingly being recorded in systematic imaging studies that generate large data sets. To maximize the usefulness of these data there is a need for improved resources for analyzing and sharing behavior data that will encourage re-analysis and method development by computational scientists1. However, unlike genomic or protein structural data, there are no widely used standards for behavior data. It is therefore desirable to make the data available in a relatively raw form so that different investigators can use their own representations and derive their own features. For computational ethology to approach the level of maturity of other areas of bioinformatics, we need to address at least three challenges: storing and accessing video files, defining flexible data formats to facilitate data sharing, and making software to read, write, browse, and analyze the data. We have developed an open resource to begin addressing these challenges using worm tracking as a model.

animal behavior and cognition↗

bioRxiv2018

Initial Characterization of the Two ClpP Paralogs of Chlamydia trachomatis Suggests Unique Functionality for Each

Chlamydia is an obligate intracellular bacterium that differentiates between two distinct functional and morphological forms during its developmental cycle: elementary bodies (EBs) and reticulate bodies (RBs). EBs are non-dividing, small electron dense forms that infect host cells. RBs are larger, non-infectious replicative forms that develop within a membrane-bound vesicle, termed an inclusion. Given the unique properties of each developmental form of this bacterium, we hypothesized that the Clp protease system plays an integral role in proteomic turnover by degrading specific proteins from one developmental form or the other. Chlamydia has five uncharacterized clp genes: clpX, clpC, two clpP paralogs, and clpB. In other bacteria, ClpC and ClpX are ATPases that unfold and feed proteins into the ClpP protease to be degraded, and ClpB is a deaggregase. Here, we focused on characterizing the ClpP paralogs. Transcriptional analyses and immunoblotting determined these genes are expressed mid-cycle. Bioinformatic analyses of these proteins identified key residues important for activity. Over-expression of inactive clpP mutants in Chlamydia suggested independent function of each ClpP paralog. To further probe these differences, we determined interactions between the ClpP proteins using bacterial two-hybrid assays and native gel analysis of recombinant proteins. Homotypic interactions of the ClpP proteins, but not heterotypic interactions between the ClpP paralogs, were detected. Interestingly, ClpP2, but not ClpP1, protease activity was detected in vitro. This activity was stimulated by antibiotics known to activate ClpP, which also blocked chlamydial growth. Our data suggest the chlamydial ClpP paralogs likely serve distinct and critical roles in this important pathogen.\n\nImportanceChlamydia trachomatis is the leading cause of preventable infectious blindness and of bacterial sexually transmitted infections worldwide. Chlamydiae are developmentally regulated, obligate intracellular pathogens that alternate between two functional and morphologic forms with distinct repertoires of proteins. We hypothesize that protein degradation is a critical aspect to the developmental cycle. A key system involved in protein turnover in bacteria is the Clp protease system. Here, we characterized the two chlamydial ClpP paralogs by examining their expression in Chlamydia, their ability to oligomerize, and their proteolytic activity. This work will help understand the evolutionarily diverse Clp proteases in the context of intracellular organisms, which may aid in the study of other clinically relevant intracellular bacteria.

microbiology↗

bioRxiv2018

Continuous State HMMs for Modeling Time Series Single Cell RNA-Seq Data

MotivationMethods for reconstructing developmental trajectories from time series single cell RNA-Seq (scRNA-Seq) data can be largely divided into two categories. The first, often referred to as pseudotime ordering methods, are deterministic and rely on dimensionality reduction followed by an ordering step. The second learns a probabilistic branching model to represent the developmental process. While both types have been successful, each suffers from shortcomings that can impact their accuracy.\n\nResultsWe developed a new method based on continuous state HMMs (CSHMMs) for representing and modeling time series scRNA-Seq data. We define the CSHMM model and provide efficient learning and inference algorithms which allow the method to determine both the structure of the branching process and the assignment of cells to these branches. Analyzing several developmental single cell datasets we show that the CSHMM method accurately infers branching topology and correctly and continuously assign cells to paths, improving upon prior methods proposed for this task. Analysis of genes based on the continuous cell assignment identifies known and novel markers for different cell types.\n\nAvailabilitySoftware and Supporting website: www.andrew.cmu.edu/user/chiehll/CSHMM/\n\nContactzivbj@cs.cmu.edu\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

systems biology↗

bioRxiv2018

Quick and efficient approach to develop genomic resources in orphan species: application in Lavandula angustifolia

Next-Generation Sequencing (NGS) technologies, by reducing the cost and increasing the throughput of sequencing, have opened doors of research efforts to generate genomic data to a range of previously poorly studied species. In this study, we proposed a method for the rapid development of a large scale molecular resources for orphan species. We studied as an example Lavandula angustifolia, a perennial sub-shrub plant native from the Mediterranean region and whose essential oil have numerous applications in cosmetics, pharmaceuticals, and alternative medicines.\n\nWe first built a Maillette reference Unigene, compound of coding sequences, thanks to de novo RNA-seq assembly. Then, we reconstructed the complete genes sequences (with exons and introns) using a transcriptome-guided DNA-seq assembly approach in order to maximize the possibilities of finding polymorphism between genetically close individuals. Finally, we used these resources for SNP mining within a collection of 16 lavender clones and tested the SNP within the scope of a phylogeny analysis. We obtained a cleaned reference of 8, 030 functionally annotated genes (in silico annotation). We found up to 400K polymorphic sites, depending on the genotype analyzed, and observed a high SNP frequency (mean of 1 SNP per 90 bp) and a high level of heterozygosity (more than 60% of heterozygous SNP per genotype). We found similar genetic distances between pairs of clones, related to the out-crossing nature of the species, the restricted area of cultivation and the clonal propagation of the varieties.\n\nThe method propose is transferable to other orphan species, requires little bioinformatics resources and can be realized within a year. This is the first reported large-scale SNP development on Lavandula angustifolia. All this data provides a rich pool of molecular resource to explore and exploit biodiversity in breeding programs.

genomics↗

bioRxiv2018

Genome-wide identification and functional analysis of circRNAs in Zea mays

Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs, which increasingly drawn researchers attention in recent years as their importance in regulating gene expression at the transcriptional and post-transcriptional levels. With the development of high-throughput sequencing and bioinformatics, circRNAs have been widely analysed in animals, but the understanding of characteristics and function of circRNAs is limited in plants, especially in maize. Here, 3715 unique circRNAs were predicted in Zea mays systematically, and 8 of 12 circRNAs were validated by experiments. By analysing circRNA sequence, the events of alternative circularization phenomenon were found prevailed in maize. By comparing circRNAs in different species, it showed that part circRNAs are conserved across species, for example, there are 273 circRNAs conserved between maize and rice. Although most of the circRNAs have low expression levels, we found 213 differential expressed circRNAs responding to heat, cold, or drought, and 1782 tissue-specific expressed circRNAs. The results showed that those circRNAs may have potential biological functions in specific situations. Finally, two different methods were used to search circRNA functions, which were based on circRNAs originated from protein-coding genes and circRNAs as miRNA decoys. 346 circRNAs could act as miRNA decoys, which might modulate the effects of multiple molecular functions, including binding, catalytic activity, oxidoreductase activity, and transmembrane transporter activity. Maize circRNAs were identified, classified and characterized systematically. We also explored circRNA functions, suggesting that circRNAs are involved in multiple molecular processes and play important roles in regulating of gene expression. Our results provide a rich resource for further study of maize circRNAs.

genetics↗

bioRxiv2018

Etiology of fever in Ugandan children: identification of microbial pathogens using metagenomic next-generation sequencing and IDseq, a platform for unbiased metagenomic analysis

BackgroundFebrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. We built and employed IDseq, a cloud-based, open access, bioinformatics platform and service to identify microbes from metagenomic next-generation sequencing of tissue samples. In this pilot study, we evaluated blood, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda.\n\nResultsThe most common pathogens identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from blood; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. Among other potential pathogens, we identified one novel orthobunyavirus, tentatively named Nyangole virus, from the blood of a child diagnosed with malaria and pneumonia, and Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis. We also identified two novel human rhinovirus C species.\n\nConclusionsThis exploratory pilot study demonstrates the utility of mNGS and the IDseq platform for defining the molecular landscape of febrile infectious diseases in resource limited areas. These methods, supported by a robust data analysis and sharing platform, offer a new tool for the surveillance, diagnosis, and ultimately treatment and prevention of infectious diseases.

genomics↗

bioRxiv2018

Common ancestry of heterodimerizing TALE homeobox transcription factors across Metazoa and Archaeplastida

Homeobox transcription factors (TFs) in the TALE superclass are deeply embedded in the gene regulatory networks that orchestrate embryogenesis. Knotted-like homeobox (KNOX) TFs, homologous to animal MEIS, have been found to drive the haploid-to-diploid transition in both unicellular green algae and land plants via heterodimerization with other TALE superclass TFs, representing remarkable functional conservation of a developmental TF across lineages that diverged one billion years ago. To delineate the ancestry of TALE-TALE heterodimerization, we analyzed TALE endowment in the algal radiations of Archaeplastida, ancestral to land plants. Homeodomain phylogeny and bioinformatics analysis partitioned TALEs into two broad groups, KNOX and non-KNOX. Each group shares previously defined heterodimerization domains, plant KNOX-homology in the KNOX group and animal PBC-homology in the non-KNOX group, indicating their deep ancestry. Protein-protein interaction experiments showed that the TALEs in the two groups all participated in heterodimerization. These results indicate that the TF dyads consisting of KNOX/MEIS and PBC-containing TALEs must have evolved early in eukaryotic evolution, a likely function being to accurately execute the haploid-to-diploid transitions during sexual development.\n\nAuthor summaryComplex multicellularity requires elaborate developmental mechanisms, often based on the versatility of heterodimeric transcription factor (TF) interactions. Highly conserved TALE-superclass homeobox TF networks in major eukaryotic lineages suggest deep ancestry of developmental mechanisms. Our results support the hypothesis that in early eukaryotes, the TALE heterodimeric configuration provided transcription-on switches via dimerization-dependent subcellular localization, ensuring execution of the haploid-to-diploid transition only when the gamete fusion is correctly executed between appropriate partner gametes, a system that then diversified in the several lineages that engage in complex multicellular organization.

evolutionary biology↗

bioRxiv2018

Flux balance analysis predicts NADP phosphatase and NADH kinase are critical to balancing redox during xylose fermentation in Scheffersomyces stipitis

Xylose is the second most abundant sugar in lignocellulose and can be used as a feedstock for next-generation biofuels by industry. Saccharomyces cerevisiae, one of the main workhorses in biotechnology, is unable to metabolize xylose natively but has been engineered to ferment xylose to ethanol with the xylose reductase (XR) and xylitol dehydrogenase (XDH) genes from Scheffersoymces stipitis. In the scientific literature, the yield and volumetric productivity of xylose fermentation to ethanol in engineered S. cerevisiae still lags S. stipitis, despite expressing of the same XR-XDH genes. These contrasting phenotypes can be due to differences in S. cerevisiaes redox metabolism that hinders xylose fermentation, differences in S. stipitis redox metabolism that promotes xylose fermentation, or both. To help elucidate how S. stipitis ferments xylose, we used flux balance analysis to test various redox balancing mechanisms, reviewed published omics datasets, and studied the phylogeny of key genes in xylose fermentation. In vivo and in silico xylose fermentation cannot be reconciled without NADP phosphatase (NADPase) and NADH kinase. We identified eight candidate genes for NADPase. PHO3.2 was the sole candidate showing evidence of expression during xylose fermentation. Pho3.2p and Pho3p, a recent paralog, were purified and characterized for their substrate preferences. Only Pho3.2p was found to have NADPase activity. Both NADPase and NAD(P)H-dependent XR emerged from recent duplications in a common ancestor of Scheffersoymces and Spathaspora to enable efficient xylose fermentation to ethanol. This study demonstrates the advantages of using metabolic simulations, omics data, bioinformatics, and enzymology to reverse engineer metabolism.

microbiology↗

bioRxiv2018

Integrative analysis of transcriptomic and clinical data uncovers the tumor suppressive activity of MITF in prostate cancer.

The dysregulation of gene expression is an enabling hallmark of cancer. Computational analysis of transcriptomics data from human cancer specimens, complemented with exhaustive clinical annotation, provides an opportunity to identify core regulators of the tumorigenic process. Here we exploit well-annotated clinical datasets of prostate cancer for the discovery of transcriptional regulators relevant to prostate cancer. Following this rationale, we identify Microphthalmia-associated transcription factor (MITF) as a prostate tumor suppressor among a subset of transcription factors. Importantly, we further interrogate transcriptomics and clinical data to refine MITF perturbation-based empirical assays and unveil Crystallin Alpha B (CRYAB) as an unprecedented direct target of the transcription factor that is, at least in part, responsible for its tumor suppressive activity in prostate cancer. This evidence was supported by the enhanced prognostic potential of a signature based on the concomitant alteration of MITF and CRYAB in prostate cancer patients. In sum, our study provides proof-of-concept evidence of the potential of the bioinformatics screen of publicly available cancer patient databases as discovery platforms, and demonstrates that the MITF-CRYAB axis controls prostate cancer biology.

cancer biology↗

bioRxiv2018

Therapeutic effects of Hypoxia-Inducible Factor-1α (HIF-1α) on bone formation around implants in diabetic mice

Patients with uncontrolled diabetes are susceptible to implant failure due to impaired bone metabolism. Hypoxia-Inducible Factor 1 (HIF-1), a transcription factor that is up-regulated in response to reduced oxygen condition during the bone repair process after fracture or osteotomy, is known to mediate angiogenesis and osteogenesis. However, its function is inhibited under hyperglycemic conditions in diabetic patients. The aim of this study is to evaluate the effects of exogenous HIF-1 on bone formation around implants by applying HIF-1 to diabetic mice via a novel PTD-mediated DNA delivery system. Smooth surface implants (1mm in diameter; 2mm in length) were placed in the both femurs of diabetic and normal mice. HIF-1 and placebo gels were injected to implant sites of the right and left femurs, respectively: Normal mouse with HIF-1 gel (NH), Normal mouse with placebo gel (NP), Diabetic mouse with HIF-1 gel (DH), and Diabetic mouse with placebo gel (DP). RNA sequencing was performed 4 days after surgery. Based on RNA sequencing, Differentially Expressed Genes (DEGs) were identified and HIF-1 target genes were selected. Histologic and histomorphometric results were evaluated 2 weeks after the surgery. The results showed that bone-to-implant contact (BIC) and bone volume (BV) were significantly greater in the DH group than the DP group (p < 0.05). A total of 216 genes were differentially expressed in DH group compared to DP group. On the other hand, there were 95 DEGs in the case of normal mice. Twenty-one target genes of HIF-1 were identified in diabetic mice through bioinformatic analysis of DEGs. Among the target genes, NOS2, GPNMB, CCL2, CCL5, CXCL16 and TRIM63 were manually found to be associated with wound healing-related genes. In conclusion, local administration of HIF-1 via PTD may help bone formation around the implant and induce gene expression more favorable to bone formation in diabetic mice.

molecular biology↗