Unified Feature Association Networks through Integration of Transcriptomic and Proteomic Data
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (human) Dengue Virus
TISSUE(S): U-937 Cell
SUBMITTER: 
Matthew Monroe
LAB HEAD: Joshua N. Adkins
PROVIDER: PXD014780 | Pride | 2019-08-22
REPOSITORIES: Pride
Publications
Unified feature association networks through integration of transcriptomic and proteomic data.
McClure Ryan S RS Wendler Jason P JP Adkins Joshua N JN Swanstrom Jesica J Baric Ralph R Kaiser Brooke L Deatherage BLD Oxford Kristie L KL Waters Katrina M KM McDermott Jason E JE
PLoS computational biology 20190917 9
High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding netwo ...[more]
Similar Datasets
Project description:DC-SIGN is a C-type lectin expressed by dendritic cells (DCs) that binds HIV-1, sequestering it within multivesicular bodies to facilitate transmission to CD4+ T cells. Here we characterize the molecular basis of signalling through DC-SIGN by large-scale gene expression profiling and phosphoproteome analysis. Solitary DC-SIGN activation leads to a phenotypically disparate transcriptional program from Toll-like receptor (TLR) triggering with downregulation of MHC II, CD86, and interferon response genes and with induction of the TLR negative regulator ATF3. Phosphoproteome analysis reveals DC-SIGN signals through the leukemia-associated Rho guanine nucleotide exchange factor (LARG) to induce Rho activity. This LARG activation also occurs on DC HIV exposure and is required for effective HIV viral synapse formation. Taken together HIV mediated DC-SIGN signalling provides a mechanism by which HIV evades the immune response yet induces viral spread. Keywords: Activation state, signalling, Toll-like Receptor (TLR)
2007-04-24 | GSE6090 | GEO
Project description:DC-SIGN is a C-type lectin expressed by dendritic cells (DCs) that binds HIV-1, sequestering it within multivesicular bodies to facilitate transmission to CD4+ T cells. Here we characterize the molecular basis of signalling through DC-SIGN by large-scale gene expression profiling and phosphoproteome analysis. Solitary DC-SIGN activation leads to a phenotypically disparate transcriptional program from Toll-like receptor (TLR) triggering with downregulation of MHC II, CD86, and interferon response genes and with induction of the TLR negative regulator ATF3. Phosphoproteome analysis reveals DC-SIGN signals through the leukemia-associated Rho guanine nucleotide exchange factor (LARG) to induce Rho activity. This LARG activation also occurs on DC HIV exposure and is required for effective HIV viral synapse formation. Taken together HIV mediated DC-SIGN signalling provides a mechanism by which HIV evades the immune response yet induces viral spread. Experiment Overall Design: Circulating monocyte derived DCs were isolated from buffy coats by adherence and culture in IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF). DC preparations analyzed were more than 98% pure. At day four 10 million immature DCs were either left unstimulated or stimulated using plate bound anti-DC-SIGN antibody for 2 hr. Three replicates of non-stimulated or stimulated cells were taken and used to extract total RNA.
2008-06-14 | E-GEOD-6090 | biostudies-arrayexpress
Project description:CEM.NKR.DC-SIGN cells were infected in vitro with DENV1 (strain WestPac74) for 18 hours, after which either total viable cells or viable cells expressing surface DENV1 NS1 were isolated by flow cytometric sorting. Sorted cells were processed for scRNAseq analysis using either a standard Oligo(dT) primer, or an Oligo(dT) primer supplemented with a DENV-specific RT primer
2020-05-17 | GSE147103 | GEO
Project description:DC-SIGN+ monocyte-derived dendritic cells (mo-DCs) play important roles in bacterial infections and inflammatory diseases, but the factors regulating their differentiation and proinflammatory status remain poorly defined. Here, we identify a micro-RNA, miR-181a, and a molecular mechanism that simultaneously regulate the acquisition of DC-SIGN+ expression and the activation state of DC-SIGN+ mo-DCs. Specifically, we show that miR-181a promotes DC-SIGN expression during terminal mo-DC differentiation and limits its sensitivity and responsiveness to TLR triggering and CD40 ligation. Mechanistically, miR-181a sustains ERK-MAPK signaling in mo-DCs, thereby enabling the maintenance of high levels of DC-SIGN and a high activation threshold. Low miR-181a levels during mo-DC differentiation, induced by inflammatory signals, do not support the high phospho-ERK signal transduction required for DC-SIGNhi mo-DCs and lead to development of proinflammatory DC-SIGNlo/- mo-DCs. Collectively, our study demonstrates that high DC-SIGN expression levels and a high activation threshold in mo-DCs are linked and simultaneously maintained by miR-181a.
2020-03-10 | GSE96847 | GEO
Project description:Here; we have described and tested a microarray based-method for the screening of dengue virus (DENV) serotypes. This DNA microarray assay is specific and sensitive and can detect dual infections with two dengue virus serotypes and single-serotype infections. Other methodologies may underestimate samples containing more than one serotype. This technology can be used to discriminate between the four DENV serotypes. Single-stranded DNA targets were covalently attached to glass slides and hybridised with specific labelled probes. DENV isolates and dengue samples were used to evaluate microarray performance. Our results demonstrate that the probes hybridized specifically to DENV serotypes; with no detection of unspecific signals. This finding provides evidence that specific probes can effectively identify single and double infections in DENV samples. Background Dengue is a mosquito-borne viral infection causing a major public health problem globally. Dengue virus (DENV) is the causative agent of dengue fever (DF) and dengue hemorrhagic fever (DHF) and includes four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4). DENV-2 and DENV-3 have been associated with severe dengue disease, consequently, laboratory testing for DENV is needed to confirm the diagnosis of DENV infection, serotype and to differentiate dengue from other febrile tropical illnesses. In addition, surveillance of mosquitoes infected with DENV is needed to monitor the infection rates within vector mosquito populations harboring specific serotype to provide an early warning sign to predict epidemics. Results In this work we have applied microarray analysis to simultaneously determine the serotype of multiple RNA samples from human or mosquitoes. The proposed microarray method can be used for i) rapid and reliable dengue diagnosis; ii) serotyping and iii) surveillance of mosquitoes infected with dengue. These microarrays were useful to confirm the presence of DENV-2 in 94 serum samples, DENV-3 in three samples from Juchitan, Oaxaca and one case from Juchitan, Oaxaca contained DENV-2 and -3. Moreover by using these microarrays we also determined DENV in pools of gravid females mosquitoes collected in several sites of nineteen Mexican states in 2005. Mosquito pools from 31 cities in the states of Yucatan, Campeche, Tabasco, Chiapas, Veracruz, Oaxaca, Guerrero, Tamaulipas and Colima were infected with DENV-2, six cities in Yucatán, Tabasco, Morelos, Tamaulipas, Colima, and Nayarit with DENV-1, three from Tabasco, Veracruz and Oaxaca with DENV 3 and two with two serotypes simultaneously (Ciudad Mante with DENV-1 and DENV-2, and Tavela with DENV-2 and DENV-3). Conclusion Here we show the success of applying microarrays assay to provide a consistently robust qualitative detection of dengue serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) in serum samples from patients or in pools of gravid female mosquitoes collected in the field of nineteen Mexican states. Interestingly, we did not detect any mosquito or serum sample containing DENV-4.
2015-11-30 | GSE26943 | GEO
Project description:Here we investigate the relevance of the microenvironment in follicular lymphoma by studying the effect of the lectin DC-SIGN, expressed by macrophages on B-cell receptor activation. We compare the effect of DC-SIGN and anti-IgM stimulation on FL by treating 3 FL samples with 20 μg/ml of goat F(ab’)2 anti-IgM, 20 μg/ml of DC-SIGN-Fc or left untreated for 4 hours at 37°C. Total RNA was extracted using an RNeasy mini kit (Qiagen) and polyA libraries were 75bp PE sequenced on a HiSeq4000 (Ilumina). After gene expression profiling analysis we found that, although DC-SIGN-Fc appears to elicit a weaker transcriptional response than anti-IgM, the responses are closely related and encompass a wide range of canonical BCR response pathways.
2020-01-31 | E-MTAB-8708 | biostudies-arrayexpress
Project description:Dengue virus (DENV) infects hundreds of millions of people annually, yet there is only a limited knowledge of the host immune response to dengue. Here, we used a systems biological approach to perform a detailed analysis of the innate immune response to DENV infection in the whole blood samples of acutely infected humans in Bangkok, Thailand. Transcriptomic analysis revealed that genes encoding pro-inflammatory mediators and type I IFN related proteins, were associated with high levels of virus during the first few days of infection. Individuals with low or negative viremia at the late stage of fever were enriched with genes associated with pathways involved in cell cycle, proliferation, cell metabolism and translational control. Meta-analysis showed significant enrichment in genes specific for innate cells (monocytes, macrophages and DCs) in the specimens with high VL and enrichment in genes specific for NK cells, CD4+ and CD8+ T cells as well as B cells in specimens with low VL. Furthermore, flow cytometric analysis revealed an expansion in the numbers of CD14+CD16+ monocytes and depletion of CD14dimCD16++ cells and BDCA-1+ myeloid DC in blood. Consistent with this, in a non-human primate model, infection with DENV boosted the numbers of CD14+CD16+ monocytes in the blood and in secondary lymphoid organs. In vitro, freshly isolated blood monocytes infected with DENV up regulated CD16 and mediated robust differentiation of resting B cells to CD27++CD38++ plasmablasts and IgG and IgM secretion. Taken together, these data provide a detailed picture of the innate response to dengue infection in humans, and highlight an unappreciated role for CD14+CD16+ monocytes in promoting the differentiation of plasmablasts and mediating antibody response to DENV. We analyzed whole blood samples from 28 dengue patients (DF n=18, DHF=10) hospitalized at the Siriraj Hospital in Bangkok, Thailand during the season of 2009 The specimens were acquired between days 2 and 9 after onset of symptoms (acute illness), and for 19 patients (DF n=13, DHF=6) also at the convalescence at 4 weeks or later after discharge. Additionally, blood was sampled from 9 healthy, non-infected donors to provide controls for transcriptomic and immunological analysis.
2014-06-27 | E-GEOD-51808 | biostudies-arrayexpress
Project description:Previous microarray data indicated a significant increase in interferon (IFN) stimulated gene expression in cells exposed to conditioned medium from primary human trophoblasts compared to non conditioned medium. Here we want to compare the effects of conditioned media, non conditioned media, and non conditioned media spiked with 100 units of IFN beta in wild type HT1080 cells as well as in HT1080 cells deficient in STAT1 (a key signaling molecular in the IFN pathway). Interferon stimulated genes (ISGs) target viruses at various stages of their infectious life cycles, including at the earliest stage of viral entry. Here we identify ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2) as a gene upregulated by type I IFN treatment in a STAT1-dependent manner. ADAP2 functions as a GTPase-activating protein (GAP) for Arf6 and binds to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and PI(3,4)P2. We show that overexpression of ADAP2 suppresses dengue virus (DENV) and vesicular stomatitis virus (VSV) infection in an Arf6 GAP activity-dependent manner, while exerting no effect on coxsackievirus B (CVB) or Sendai virus (SeV) replication. We further show that ADAP2 expression induces macropinocytosis and that ADAP2 strongly associates with actin-enriched membrane ruffles and with Rab8a- and LAMP1-, but not EEA1- or Rab7-, positive vesicles. Utilizing two techniques—light-sensitive neutral red (NR)-containing DENV and fluorescence assays for virus internalization—we show that ADAP2 primarily restricts DENV infection at the stage of virion entry and/or intracellular trafficking and that incoming DENV and VSV particles associate with ADAP2 during their entry. Taken together, this study identifies ADAP2 as an ISG that exerts antiviral effects against RNA viruses by altering Arf6-mediated trafficking to disrupt viral entry. compare the cells exposed to CM and the cells exposed to NC media spiked with IFN to the control NC exposed cells, in wild type (2f-TGH) vs Stat -/- cells (HT1080U3A)
2015-08-26 | E-GEOD-72342 | biostudies-arrayexpress
Project description:Differential expression was determined in Calu-3 cells between mock infected and infected with H1N1 influenza virus A/Netherlands/602/2009 at nine time points post-infection. As a comparison, cells were also infected with A/CA/04/2009 H1N1 influenza virus at 4 time points post-infection.
2012-09-13 | GSE40844 | GEO
Project description:Dengue viruses (DENV) are generally maintained in a cycle which requires horizontal transmission via their arthropod vector, Ae. Aegypti, to the vertebrate host. One important consequence of this process is the interference of these arboviruses with both invertebrate and vertebrate immune systems. While infection of vertebrates causes disease, the presence of DENV gives rise to life-long, persistent infection in mosquitoes. The results of a comparative transcriptome analysis between DENV-infected and uninfected salivary glands revealed activation of both the immune deficiency (IMD) and the Toll pathways, as well as involvement of the putative antibacterial cecropin-like peptide (AAEL000598), in controlling DENV infection in Ae. aegypti. The mature form of this peptide was found to be active against DENV and Chikungunya viruses, whereas its precursor also had a strong anti-Leishmania effect. This study is the first to establish a comparative transcriptome analysis of DENV-infected and uninfected salivary glands and demonstrates that certain DENV-induced peptides, that are part of the IMD pathway, possess broad-spectrum anti-pathogenic activity and may have therapeutic potential in human. Infectious blood meals were offered to 3-day-old, adult, female Ae. aegypti Liverpool mosquitoes using a silicone membrane feeder system (Alto et al., 2005). Human blood was combined with DENV-2 16681 to provide a blood meal titer of 5.106 plaque forming units (PFU)/ml. At different time-points after the blood meal, salivary glands were dissected in acid guanidium thiocyanate-phenol-chloroform (RNAble; Eurobio, France) or phosphate-buffered saline (PBS), and the samples were frozen at -70°C until use.
2011-03-21 | E-GEOD-21528 | biostudies-arrayexpress