String Web Research Articles

VWCE as a potential biomarker associated with immune infiltrates in breast cancer

PurposeVon Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer.MethodsThe expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry.ResultsThe results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = − 0.12, p = 6e−05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer.ConclusionsIn our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.

An approach to BPS black hole microstate counting in an N = 2 STU model

We consider four-dimensional dyonic single-center BPS black holes in the N = 2 STU model of Sen and Vafa. By working in a region of moduli space where the real part of two of the three complex scalars S, T , U are taken to be large, we evaluate the quantum entropy function for these BPS black holes. In this regime, the subleading corrections point to a microstate counting formula partly based on a Siegel modular form of weight two. This is supplemented by another modular object that takes into account the dependence on Y0, a complex scalar field belonging to one of the four off-shell vector multiplets of the underlying supergravity theory. We also observe interesting connections to the rational Calogero model and to formal deformation of a Poisson algebra, and suggest a string web picture of our counting proposal.

Comprehensive Analysis of Candidate Diagnostic and Prognostic Biomarkers Associated with Lung Adenocarcinoma.

BackgroundWe aimed to screen and identify central genetic and molecular targets involved in advancement of lung adenocarcinoma (LUAD) and to perform an integrated analysis and clinical validation.Material/MethodsThe GEO2R technique was utilized to assess differentially expressed genes (DEGs) among the gene sets GSE75037, GSE85716, and GSE118370. Subsequently, gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) analytical methods were executed to determine related biofunctions and signaling pathways, which were annotated with tools from the Database for Annotation, Visualization and Integrated Discovery (DAVID) resource. Then, a protein-protein interaction (PPI) network complex consisting of all detected DEGs was built with the STRING web interface. Cytohubba and MCODE plug-ins for Cytoscape software and Gene Expression Profiling Interactive Analysis (GEPIA) were employed to identify the hub genes. Finally, the mRNA expression of the identified hub genes was quantitatively validated by The Cancer Genome Atlas (TCGA) database analysis and real-time quantitative polymerase chain reaction (RT-qPCR).ResultsWe screened 146 upregulated DEGs and 431 downregulated DEGs with the criteria of |logFC| >1 and P<0.05, and the GO analysis indicated that DEGs were implicated in mitotic nuclear division (biological process, BP), the nucleus (cellular component, CC), and protein binding (molecular function, MF) and were associated with multiple KEGG pathways, such as the p53 signaling pathway in cancer. Then, the top 8 genes that predicted significantly different outcomes in LUAD patients were filtered from the DEGs and selected as hub genes. The TCGA database analysis and RT-qPCR results demonstrated that these genes were differentially expressed with the same trends in LUAD tissues compared with normal tissues.ConclusionsOverall, we propose that 8 genes (PECAM1, CDK1, MKI67, SPP1, TOP2A, CHEK1, CCNB1, and RRM2) might be novel hub genes strongly associated with the progression and prognosis of LUAD.

Mining the proliferative diabetic retinopathy-associated genes and pathways by integrated bioinformatic analysis.

Diabetic retinopathy (DR) especially proliferative diabetic retinopathy (PDR) is a serious eye disease. We aimed to identify key pathway and hub genes associated with PDR by analyzing the expression of retinal fibrovascular tissue in PDR patients. First raw data were downloaded from the Gene Expression Omnibus database. Median normalization was subsequently applied to preprocess. Differentially expressed genes (DEGs) analyzed with the Limma package. Weighted correlation network analysis (WGCNA) was utilized to build the co-expression network for all genes. Then, we compared the DEGs and modules filtered out by WGCNA. A protein-protein interaction network based on the STRING web site and the Cytoscape software was constructed by the overlapping DEGs. Next, the Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Finally, we used the Comparative Toxicogenomics Database to identify some important pathways and hub genes tightly related to PDR. Functional enrichment analysis showed that the pathway of cytokine-cytokine receptor interaction was significantly related to PDR eight hub genes which were associated with pathway including tumor necrosis factor (TNF), tumor necrosis factor receptor superfamily member 12A (TNFRSF12A), C-C chemokine 20 (CCL20), chemokine (C-X-C motif) ligand 2 (CXCL2), oncostatin M (OSM) interleukin 10 (IL10), interleukin 15 (IL 15), and interleukin 1B (IL1B). We identified one pathway and eight hub genes, which were associated with PDR. The pathway provided references that will advance the understanding of mechanisms of PDR. Moreover, the hub genes may serve as therapeutic targets for precise diagnosis and treatment of PDR in the future.

MiRNA deregulation targets specific pathways in leiomyosarcoma development: an in silico analysis

BackgroundMicroRNA (miRNA) mediate post-transcriptional gene repression and are involved in a variety of human diseases, including cancer. Soft tissue sarcomas are rare malignancies with a variety of histological subtypes which may occur virtually anywhere in the human body. Leiomyosarcoma is one of the most common subtypes, shows a smooth muscle phenotype and its cancerogenesis is still unclear. The aim of our study was to investigate the potential role of miRNA differential expression in leiomyosarcoma development.MethodsWe first employed the Sarcoma microRNA Expression Database, a repository that describes the patterns of over 1000 miRNA expression in various human sarcoma types, to identify differentially expressed miRNA comparing leiomyosarcoma and smooth muscle samples. Subsequently, we identified putative target genes of those miRNAs with the TargetScan prediction tool. Finally, we evaluated whether the retrieved pool of putative targets was enriched in genes belonging to specific molecular pathways by means of the Enrichr analysis tool. Protein–protein network analysis was analyzed by means of the STRING web tool.ResultsOut of 1120 miRNAs tested, the expression of 301 miRNAs was statistically significantly different between leiomyosarcoma and smooth muscle samples. The hypothetical targets could be predicted for 172 miRNAs. 438 genes were predicted to be the targets with high confidence (cumulative weighted context score cut-off level less than − 1.0) and analyzed for belonging to specific molecular pathways. Pathway analysis suggested that RNA Polymerase III, tRNA functions and synaptic neurotransmission (with special regard to dopamine mediated signaling) could be involved in leiomyosarcoma development.ConclusionsOur results demonstrate that data mining of publicly available repositories can be useful to suggest molecular pathways underlying the pathogenesis of rare tumors such as leiomyosarcoma.

Flavor symmetries and the topology of special K\xe4hler structures at rank 1

We propose a method for determining the flavor charge lattice of the continuous flavor symmetry of rank-1 4d mathcal{N} = 2 superconformal field theories (SCFTs) and IR free gauge theories from topological invariants of the special Kähler structure of the mass-deformed Coulomb branches (CBs) of the theories. The method is based on the middle homology of the total space of the elliptic fibration over the CB, and is a generalization of the F-theory string web description of flavor charge lattices. The resulting lattices, which we call “string web lattices”, contain not only information about the flavor symmetry of the SCFT but also additional information encoded in the lattice metric derived from the middle homology intersection form. This additional information clearly reflects the low energy electric and magnetic charges of BPS states on the CB, but there are other properties of the string web lattice metric which we have not been able to understand in terms of properties of the BPS spectrum. We compute the string web lattices of all rank-1 SCFTs and IR free gauge theories. We find agreement with results obtained by other methods, and find in a few cases that the string web lattice gives additional information on the flavor symmetry.

Neural stem cells isolated from amyloid precursor protein-mutated mice for drug discovery

To develop an in vitro model based on neural stem cells derived from transgenic animals, to be used in the study of pathological mechanisms of Alzheimer's disease and for testing new molecules. Neural stem cells (NSCs) were isolated from the subventricular zone of Wild type (Wt) and Tg2576 mice. Primary and secondary neurosphere generation was studied, analysing population doubling and the cell yield per animal. Secondary neurospheres were dissociated and plated on MCM Gel Cultrex 2D and after 6 d in vitro (DIVs) in mitogen withdrawal conditions, spontaneous differentiation was studied using specific neural markers (MAP2 and TuJ-1 for neurons, GFAP for astroglial cells and CNPase for oligodendrocytes). Gene expression pathways were analysed in secondary neurospheres, using the QIAGEN PCR array for neurogenesis, comparing the Tg2576 derived cell expression with the Wt cells. Proteins encoded by the altered genes were clustered using STRING web software. As revealed by 6E10 positive staining, all Tg2576 derived cells retain the expression of the human transgenic Amyloid Precursor Protein. Tg2576 derived primary neurospheres show a decrease in population doubling. Morphological analysis of differentiated NSCs reveals a decrease in MAP2- and an increase in GFAP-positive cells in Tg2576 derived cells. Analysing the branching of TuJ-1 positive cells, a clear decrease in neurite number and length is observed in Tg2576 cells. The gene expression neurogenesis pathway revealed 11 altered genes in Tg2576 NSCs compared to Wt. Tg2576 NSCs represent an appropriate AD in vitro model resembling some cellular alterations observed in vivo, both as stem and differentiated cells.

CorrelaGenes: a new tool for the interpretation of the human transcriptome

CorrelaGenes: a new tool for the interpretation of the human transcriptome

A study of Wall-Crossing: flavored kinks in D = 2 QED

We study spectrum of D=2 N=(2,2) QED with N+1 massive charged chiral multiplets, with care given to precise supermultiplet countings. In the infrared the theory flows to CP^N model with twisted masses, where we construct generic flavored kink solitons for the large mass regime, and study their quantum degeneracies. These kinks are qualitatively different and far more numerous than those of small mass regime, with features reminiscent of multi-pronged (p,q) string web, complete with the wall-crossing behavior. It has been also conjectured that spectrum of this theory is equivalent to the hypermultiplet spectrum of a certain D=4 Seiberg-Witten theory. We find that the correspondence actually extends beyond hypermultiplets in D=4, and that many of the relevant indices match. However, a D=2 BPS state is typically mapped to several different kind of dyons whose individual supermultiplets are rather complicated; the match of index comes about only after summing over indices of these different dyons. We note general wall-crossing behavior of flavored BPS kink states, and compare it to those of D=4 dyons.

STRING and STITCH: known and predicted interactions between proteins and chemicals

AbstractInformation on protein-protein and protein-chemical interactions is essential for understanding cellular functions. The STRING and STITCH web resources integrate interaction evidence derived from pathways, automatic literature mining, primary experimental data, and genomic context. The resulting interaction networks cover 1.5 million proteins from 373 organisms and 68,000 chemicals.

The Firegoose: two-way integration of diverse data from different bioinformatics web resources with desktop applications

BackgroundInformation resources on the World Wide Web play an indispensable role in modern biology. But integrating data from multiple sources is often encumbered by the need to reformat data files, convert between naming systems, or perform ongoing maintenance of local copies of public databases. Opportunities for new ways of combining and re-using data are arising as a result of the increasing use of web protocols to transmit structured data.ResultsThe Firegoose, an extension to the Mozilla Firefox web browser, enables data transfer between web sites and desktop tools. As a component of the Gaggle integration framework, Firegoose can also exchange data with Cytoscape, the R statistical package, Multiexperiment Viewer (MeV), and several other popular desktop software tools. Firegoose adds the capability to easily use local data to query KEGG, EMBL STRING, DAVID, and other widely-used bioinformatics web sites. Query results from these web sites can be transferred to desktop tools for further analysis with a few clicks.Firegoose acquires data from the web by screen scraping, microformats, embedded XML, or web services. We define a microformat, which allows structured information compatible with the Gaggle to be embedded in HTML documents.We demonstrate the capabilities of this software by performing an analysis of the genes activated in the microbe Halobacterium salinarum NRC-1 in response to anaerobic environments. Starting with microarray data, we explore functions of differentially expressed genes by combining data from several public web resources and construct an integrated view of the cellular processes involved.ConclusionThe Firegoose incorporates Mozilla Firefox into the Gaggle environment and enables interactive sharing of data between diverse web resources and desktop software tools without maintaining local copies. Additional web sites can be incorporated easily into the framework using the scripting platform of the Firefox browser. Performing data integration in the browser allows the excellent search and navigation capabilities of the browser to be used in combination with powerful desktop tools.

The Gaggle: An open-source software system for integrating bioinformatics software and data sources

BackgroundSystems biologists work with many kinds of data, from many different sources, using a variety of software tools. Each of these tools typically excels at one type of analysis, such as of microarrays, of metabolic networks and of predicted protein structure. A crucial challenge is to combine the capabilities of these (and other forthcoming) data resources and tools to create a data exploration and analysis environment that does justice to the variety and complexity of systems biology data sets. A solution to this problem should recognize that data types, formats and software in this high throughput age of biology are constantly changing.ResultsIn this paper we describe the Gaggle -a simple, open-source Java software environment that helps to solve the problem of software and database integration. Guided by the classic software engineering strategy of separation of concerns and a policy of semantic flexibility, it integrates existing popular programs and web resources into a user-friendly, easily-extended environment.We demonstrate that four simple data types (names, matrices, networks, and associative arrays) are sufficient to bring together diverse databases and software. We highlight some capabilities of the Gaggle with an exploration of Helicobacter pylori pathogenesis genes, in which we identify a putative ricin-like protein -a discovery made possible by simultaneous data exploration using a wide range of publicly available data and a variety of popular bioinformatics software tools.ConclusionWe have integrated diverse databases (for example, KEGG, BioCyc, String) and software (Cytoscape, DataMatrixViewer, R statistical environment, and TIGR Microarray Expression Viewer). Through this loose coupling of diverse software and databases the Gaggle enables simultaneous exploration of experimental data (mRNA and protein abundance, protein-protein and protein-DNA interactions), functional associations (operon, chromosomal proximity, phylogenetic pattern), metabolic pathways (KEGG) and Pubmed abstracts (STRING web resource), creating an exploratory environment useful to 'web browser and spreadsheet biologists', to statistically savvy computational biologists, and those in between. The Gaggle uses Java RMI and Java Web Start technologies and can be found at .

Pentaquark Baryons in String Theory

The recently observed pentaquark baryons $\Theta^{+}$ and $\Xi^{--}$ are studied in the dual gravity theory of QCD. By developing a general formulation useful for studying the branched string web in a curved space, simple mass formulae of the pentaquark baryons are derived in the Maldacena prototype model for supersymmetric QCD and a more realistic model for ordinary QCD. Even though the approximations adopted here in deriving these formulae are extremely naive, the predicted values of the masses do not differ significantly from their experimental values. We thus conclude that this approach is promising for the purpose of obtaining a description of the observed masses of pentaquarks and of their extremely narrow decay widths. With the aim of constructing more reliable mass formulae, a preliminary sketch is given of how spin, the hyperfine interaction and parity are considered in the string picture.

STRING WEBS AND THE DECAY OF SUPERSYMMETRIC PARTICLES

The spectrum of stable electrically and magnetically charged supersymmetric particles can change discontinously due to the decay of these particles as the vacuum on the Coulomb branch is varied. We show that this decay process is well described by semiclassical field configurations even when it occurs at strong coupling. the resulting picture of the stable supersymmetric spectrum is a generalization of the "string web" picture of these states found in string constructions.

Zero-mode dynamics of string webs

At sufficiently low energy the dynamics of a string web is dominated by zero modes involving the rigid motion of the internal strings. The dimension of the associated moduli space equals the maximal number of internal faces in the web. The generic web moduli space has boundaries and multiple branches, and for webs with three or more faces the geometry is curved. Webs can also be studied in a lift to M theory, where a string web is replaced by a membrane wrapped on a holomorphic curve in spacetime. In this case the moduli space becomes a complex manifold with a K\"ahler metric.

String webs from field theory

The spectrum of stable electrically and magnetically charged supersymmetric particles can change discontinuously as one changes the vacuum on the Coulomb branch of gauge theories with extended supersymmetry in four dimensions. We show that this decay process can be understood and is well described by semiclassical field configurations purely in terms of the low energy effective action on the Coulomb branch even when it occurs at strong coupling. The resulting picture of the stable supersymmetric spectrum is a generalization of the ``string web'' picture of these states found in string constructions for certain theories.

BPS spectrum of 5 dimensional field theories, (p,q) webs and curve counting

We study the BPS spectrum of supersymmetric 5 dimensional field theories and their representations as string webs. It is found that a state of given charges exists when it has a representation as an irreducible string web. Its spin is determined by the string web. The number of fermionic zero modes is 8g+4b, where g is the number of internal faces and b is the number of boundaries. In the lift to M theory of 4d field theories such states are described by membranes ending on the 5-brane, breaking SUSY from 8 to 4, and g becomes the genus of the membrane. Mathematically, we obtain a diagrammatic method to find the spectrum of curves on a toric complex surface, and the number of their moduli.