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BioMed Research International 2019Identification of protein complex is very important for revealing the underlying mechanism of biological processes. Many computational methods have been developed to...
Identification of protein complex is very important for revealing the underlying mechanism of biological processes. Many computational methods have been developed to identify protein complexes from static protein-protein interaction (PPI) networks. Recently, researchers are considering the dynamics of protein-protein interactions. Dynamic PPI networks are closer to reality in the cell system. It is expected that more protein complexes can be accurately identified from dynamic PPI networks. In this paper, we use the undulating degree above the base level of gene expression instead of the gene expression level to construct dynamic temporal PPI networks. Further we convert dynamic temporal PPI networks into dynamic Temporal Interval Protein Interaction Networks (TI-PINs) and propose a novel method to accurately identify more protein complexes from the constructed TI-PINs. Owing to preserving continuous interactions within temporal interval, the constructed TI-PINs contain more dynamical information for accurately identifying more protein complexes. Our proposed identification method uses multisource biological data to judge whether the joint colocalization condition, the joint coexpression condition, and the expanding cluster condition are satisfied; this is to ensure that the identified protein complexes have the features of colocalization, coexpression, and functional homogeneity. The experimental results on yeast data sets demonstrated that using the constructed TI-PINs can obtain better identification of protein complexes than five existing dynamic PPI networks, and our proposed identification method can find more protein complexes accurately than four other methods.
Topics: Algorithms; Cluster Analysis; Computational Biology; Gene Expression; Protein Interaction Maps; Proteins
PubMed: 31531351
DOI: 10.1155/2019/3726721 -
Bioscience Reports Mar 2020The dysregulation and essential role of WNTs in glioma have been widely implicated. However, there is a paucity of literature on the expression status of all the 19 WNTs...
AIMS
The dysregulation and essential role of WNTs in glioma have been widely implicated. However, there is a paucity of literature on the expression status of all the 19 WNTs in glioma. Our study was aimed to evaluate the expression and prognostic values of the 19 WNTs in glioma.
METHODS
mRNA expression and clinical data were retrieved from the Cancer Genome Atlas (TCGA) database, Chinese Glioma Genome Atlas (CGGA), GTEx and ONCOMINE databases. The 50 frequent neighbor genes of WNT5A and WNT10B were shown with PPI network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.
RESULTS
We found that the mRNA expression of WNT5A was significantly higher in glioma; however, the WNT10B expression was significantly lower in glioma. Furthermore, the expression of WNT5A and WNT10B was associated with the clinicopathology of glioma. The survival analysis revealed that the higher expressions of WNT5A and WNT16 were associated poor overall survival (OS) in patients with glioma. Conversely, overexpression of WNT3, WNT5B, and WNT10B was associated with better OS. Finally, Go and KEGG analysis revealed WNT5A was associated with multiple signal translations, and crucial oncogenes (EGFR and MDM2) and 2 important tumor suppressors (PTEN and IKN4a/ARF) were found closely correlated with WNT5A in glioma.
CONCLUSION
Among 19WNTs, WNT5A can serve as a candidate to diagnose and therapy glioma, while WNT10B might be valuable for anti-glioma research. The presumed direction was provided to explore the relation of WNTs signal and multiple pathways in glioma.
Topics: Computational Biology; Databases, Genetic; Gene Expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Glioma; Humans; Prognosis; Proto-Oncogene Proteins; Transcriptome; Wnt Proteins; Wnt-5a Protein
PubMed: 32181818
DOI: 10.1042/BSR20194255 -
Current Neuropharmacology 2017The G protein-coupled receptor 55 (GPR55) is a mammalian orphan receptor that awaits a formal classification. There are an increasing number of reports directed to know... (Review)
Review
BACKGROUND
The G protein-coupled receptor 55 (GPR55) is a mammalian orphan receptor that awaits a formal classification. There are an increasing number of reports directed to know the physiology and pathophysiology of this receptor. Lamentably, its functions in the central nervous system (CNS) have been scarcely elucidated.
METHODS
A bibliographic search in PubMed database about GPR55 actions in the CNS was made. The information was grouped for brain structures to facilitate the interpretation. Finally, we constructed a schematic representation of the current knowledge about the potential participation of GPR55 in some physiological and pathophysiological events.
RESULTS
Seventy nine papers were included in the review. Only few of them showed data about GPR55 (mRNA/protein) expression in multiple brain areas. The rest showed findings in different preparations both in vitro and in vivo conditions that allowed us to speculate a potential activity of GPR55 in the different brain areas.
CONCLUSION
GPR55 mRNA is expressed in several brain areas as the hippocampus, hypothalamus, frontal cortex and cerebellum; but due to the lack of information, only some speculative information about its function in these regions has been suggested. Therefore, this review provide relevant information to motivate further research about GPR55 physiology/pathophysiology in the CNS.
Topics: Animals; Cannabinoids; Central Nervous System; Gene Expression; Humans; Psychomotor Performance; PubMed; Receptors, Cannabinoid; Receptors, G-Protein-Coupled; Sensation
PubMed: 27488130
DOI: 10.2174/1570159X14666160729155441 -
BMC Bioinformatics Sep 2009Joint analysis of transcriptomic and proteomic data taken from the same samples has the potential to elucidate complex biological mechanisms. Most current methods that...
BACKGROUND
Joint analysis of transcriptomic and proteomic data taken from the same samples has the potential to elucidate complex biological mechanisms. Most current methods that integrate these datasets allow for the computation of the correlation between a gene and protein but only after a one-to-one matching of genes and proteins is done. However, genes and proteins are connected via biological pathways and their relationship is not necessarily one-to-one. In this paper, we investigate the use of Correlated Factor Analysis (CFA) for modeling the correlation of genome-scale gene and protein data. Unlike existing approaches, CFA considers all possible gene-protein pairs and utilizes all gene and protein information in its modeling framework. The Generalized Singular Value Decomposition (gSVD) is another method which takes into account all available transcriptomic and proteomic data. Comparison is made between CFA and gSVD.
RESULTS
Our simulation study indicates that the CFA estimates can consistently capture the dominant patterns of correlation between two sets of measurements; in contrast, the gSVD estimates cannot do that. Applied to real cancer data, the list of co-regulated genes and proteins identified by CFA has biologically meaningful interpretation, where both the gene and protein expressions are pointing to the same processes. Among the GO terms for which the genes and proteins are most correlated, we observed blood vessel morphogenesis and development.
CONCLUSION
We demonstrate that CFA is a useful tool for gene-protein data integration and modeling, where the main question is in finding which patterns of gene expression are most correlated with protein expression.
Topics: Algorithms; Computational Biology; Gene Expression; Gene Expression Profiling; Proteins
PubMed: 19723309
DOI: 10.1186/1471-2105-10-272 -
Science (New York, N.Y.) Sep 2005Genetically identical cells and organisms exhibit remarkable diversity even when they have identical histories of environmental exposure. Noise, or variation, in the... (Review)
Review
Genetically identical cells and organisms exhibit remarkable diversity even when they have identical histories of environmental exposure. Noise, or variation, in the process of gene expression may contribute to this phenotypic variability. Recent studies suggest that this noise has multiple sources, including the stochastic or inherently random nature of the biochemical reactions of gene expression. In this review, we summarize noise terminology and comment on recent investigations into the sources, consequences, and control of noise in gene expression.
Topics: Alleles; Animals; Biological Evolution; Feedback, Physiological; Gene Dosage; Gene Expression; Gene Expression Regulation; Humans; Models, Biological; Phenotype; Physiological Phenomena; Protein Biosynthesis; Proteins; Stochastic Processes; Transcription, Genetic
PubMed: 16179466
DOI: 10.1126/science.1105891 -
The Journal of Biological Chemistry Oct 2021Biochemical studies require large quantities of proteins, which are typically obtained using bacterial overexpression. However, the folding machinery in bacteria is...
Biochemical studies require large quantities of proteins, which are typically obtained using bacterial overexpression. However, the folding machinery in bacteria is inadequate for expressing many mammalian proteins, which additionally undergo posttranslational modifications (PTMs) that bacteria, yeast, or insect cells cannot perform. Many proteins also require native N- and C-termini and cannot tolerate extra tag amino acids for proper function. Tropomyosin (Tpm), a coiled coil protein that decorates most actin filaments in cells, requires both native N- and C-termini and PTMs, specifically N-terminal acetylation (Nt-acetylation), to polymerize along actin filaments. Here, we describe a new method that combines native protein expression in human cells with an intein-based purification tag that can be precisely removed after purification. Using this method, we expressed several nonmuscle Tpm isoforms (Tpm1.6, Tpm1.7, Tpm2.1, Tpm3.1, Tpm3.2, and Tpm4.2) and the muscle isoform Tpm1.1. Proteomics analysis revealed that human-cell-expressed Tpms present various PTMs, including Nt-acetylation, Ser/Thr phosphorylation, Tyr phosphorylation, and Lys acetylation. Depending on the Tpm isoform (humans express up to 40 Tpm isoforms), Nt-acetylation occurs on either the initiator methionine or on the second residue after removal of the initiator methionine. Human-cell-expressed Tpms bind F-actin differently than their Escherichia coli-expressed counterparts, with or without N-terminal extensions intended to mimic Nt-acetylation, and they can form heterodimers in cells and in vitro. The expression method described here reveals previously unknown features of nonmuscle Tpms and can be used in future structural and biochemical studies with Tpms and other proteins, as shown here for α-synuclein.
Topics: Cell Line; Gene Expression; Humans; Protein Processing, Post-Translational; Recombinant Proteins; Tropomyosin
PubMed: 34478714
DOI: 10.1016/j.jbc.2021.101154 -
Molecular Vision 2011To understand the expression of genes involved in different complement pathways in the retina and retinal pigment epithelium (RPE)/choroid under physiologic conditions...
PURPOSE
To understand the expression of genes involved in different complement pathways in the retina and retinal pigment epithelium (RPE)/choroid under physiologic conditions and how their expression is regulated by inflammatory cytokines.
METHODS
The expression of complement components of the classical pathway (CP), mannose-binding lectin (MBL) pathway, alternative pathway (AP), and terminal pathway in the retina and RPE/choroid was determined by conventional reverse transcription polymerase chain reaction (RT-PCR). The effect of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α, 20 ng/ml), interleukin (IL)-6 (10 ng/ml), interferon-gamma (IFN-γ, 100 ng/ml) or lipopolysaccharides (LPS, 1 μg/ml) on the expression of these complement component genes was tested in vitro in primary cultured RPE cells and a microglial cell line (BV2 cells) and quantified by real-time RT-PCR.
RESULTS
In the CP, complements C1qb, C1r, C1s, C2, and C4 were constitutively expressed by retina and RPE/choroid. Complement factor H and factor B of the AP as well as C3 were also detected in the retinal and RPE/choroidal tissues. In the MBL pathway, low levels of mannose-binding lectin (MBL)-associated serine protease (MASP)-1 in the retina and RPE/choroid and MASP2L in the retina were detected. Other components, including mannose-binding lectin 1 (MBL1), mannose-binding lectin 2 (MBL2), complement factor I (CFI), complement component 5 (C5) and complement factor H-related protein 1 (CFHR1), were not detected in either the retina or the RPE/choroid. The expression of CP- and AP-complement component genes in RPE and microglial cells was upregulated by interferon (IFN)-γ treatment. Treatment with TNF-α selectively upregulated the expression of C1s and C3 genes but downregulated complement factor H gene expression in RPE and microglial cells. The expression of genes involved in the MBL pathway was not affected by the inflammatory cytokines tested in this study.
CONCLUSIONS
Retina and RPE/choroid express a variety of complement components that are involved mainly in the CP and AP. RPE and microglial cells are the main sources of retinal complement gene expression. Retinal complement gene expression is regulated by inflammatory cytokines, such as IFN-γ and TNF-α.
Topics: Animals; Cell Line; Choroid; Complement System Proteins; Female; Gene Expression; Interferon-gamma; Interleukin-6; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Microglia; Retinal Pigment Epithelium; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Tumor Necrosis Factor-alpha
PubMed: 21738388
DOI: No ID Found -
Technology and Health Care : Official... 2019The human hematopoietic stem/progenitor cell 117 (HSPC117) protein is involved in many important biological processes.
BACKGROUND
The human hematopoietic stem/progenitor cell 117 (HSPC117) protein is involved in many important biological processes.
OBJECTIVE
This study was designed to identify the level of HSPC117 mRNA expression in 10 min pig tissue samples and HSPC117 subcellular localization in the PK15 cell line.
METHODS
In this study, 10 tissue samples of min pigs were collected, and EGFP-HSPC117 vectors were constructed to express EGFP-HSPC117 fusion proteins in PK15 cells.
RESULTS
HSPC117 mRNA was expressed in all of the tissue samples, although the levels of expression in fat and lung tissues were significantly lower than in other tissues (P< 0.01). After generating and detecting the EGFP-HSPC117 fusion protein, fluorescence was found to be distributed throughout the cytoplasm and nucleus during interphase; however, the fluorescence was concentrated in the nuclear area in mitotic cells.
CONCLUSIONS
These results indicate that the HSPC117 gene is expressed in many min pig tissues. The HSPC117 protein was distributed throughout the cells during interphase, but was concentrated in the nuclear area in mitotic cells.
Topics: Animals; Biological Phenomena; Cell Line; Epithelial Cells; Gene Expression; Proteins; RNA; Reverse Transcriptase Polymerase Chain Reaction; Swine
PubMed: 31045548
DOI: 10.3233/THC-199028 -
International Journal of Experimental... Jun 2016Glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are expressed in normal human skin. They are involved in murine hair follicle...
Glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are expressed in normal human skin. They are involved in murine hair follicle morphogenesis and cycling control. We hypothesize that 'GDNF and GFRα-1 protein expression in human skin undergoes age-associated alterations. To test our hypothesis, the expression of these proteins was examined in human skin specimens obtained from 30 healthy individuals representing three age groups: children (5-18 years), adults (19-60 years) and the elderly (61-81 years). Immunofluorescent and light microscopic immunohistologic analyses were performed using tyramide signal amplification and avidin-biotin complex staining methods respectively. GDNF mRNA expression was examined by RT-PCR analysis. GDNF mRNA and protein as well as GFRα-1 protein expressions were detected in normal human skin. We found significantly reduced epidermal expression of these proteins with ageing. In the epidermis, the expression was strong in the skin of children and declined gradually with ageing, being moderate in adults and weak in the elderly. In children and adults, the expression of both GDNF and GFRα-1 proteins was strongest in the stratum basale and decreased gradually towards the surface layers where it was completely absent in the stratum corneum. In the elderly, GDNF and GFRα-1 protein expression was confined to the stratum basale. In the dermis, both GDNF and GFRα-1 proteins had strong expressions in the fibroblasts, sweat glands, sebaceous glands, hair follicles and blood vessels regardless of the age. Thus there is a decrease in epidermal GDNF and GFRα-1 protein expression in normal human skin with ageing. Our findings suggest that the consequences of this is that GFRα-1-mediated signalling is altered during the ageing process. The clinical and therapeutic ramifications of these observations mandate further investigations.
Topics: Adult; Aged; Aged, 80 and over; Aging; Gene Expression; Glial Cell Line-Derived Neurotrophic Factor; Glial Cell Line-Derived Neurotrophic Factor Receptors; Humans; Middle Aged; Nerve Tissue Proteins; Skin; Young Adult
PubMed: 27346872
DOI: 10.1111/iep.12175 -
The American Journal of Pathology Mar 2002Autosomal-dominant polycystic kidney disease, one of the most frequent human genetic disorders, is genetically heterogeneous. Most cases result from mutations of PKD1 or...
Autosomal-dominant polycystic kidney disease, one of the most frequent human genetic disorders, is genetically heterogeneous. Most cases result from mutations of PKD1 or PKD2 encoding polycystin-1 or polycystin-2, respectively. Polycystin-1 is a large transmembrane protein containing several domains involved in cell-cell and/or cell-matrix interactions. Polycystin-2 is transmembrane glycoprotein sharing homology with some families of cation channels. Despite a large number of reports, the tissue distribution of these two proteins, especially of polycystin-1, is still debated. We investigated the expression pattern of PKD1 and PKD2 transcripts and proteins during human embryogenesis and kidney development, using Northern blot analysis, in situ hybridization, and immunohistochemical methods. For each gene, the expression pattern of transcripts and protein was concordant. In human 5- to 6-week-old embryos, both genes are widely expressed, mainly in neural tissue, cardiomyocytes, endodermal derivatives, and mesonephros. At this age, PKD2 but not PKD1 expression is observed in the ureteric bud and the uninduced metanephros. Thereafter, PKD2 is diffusely expressed at all stages of nephron development, whereas high PKD1 expression first appears in differentiated proximal tubules. Proximal tubule expression of both genes decreases from weeks 20 to 24 onwards. PKD1 transcripts, later restricted to distal tubules in fetal nephrogenesis, are no longer detected in adult kidneys, which nevertheless maintain a faint expression of polycystin-1, whereas persistent expression of PKD2 transcripts and protein is observed throughout nephrogenesis. Overall, contrary to previous observations, we found profound differences in the spatiotemporal expression of PKD1 and PKD2 during nephrogenesis, PKD2 being expressed earlier and more diffusely than PKD1. These data suggest that polycystins could interact with different partners, at least during kidney development.
Topics: Adult; Embryo, Mammalian; Female; Gene Expression Regulation, Developmental; Humans; Kidney; Membrane Proteins; Pregnancy; Protein Biosynthesis; Proteins; TRPP Cation Channels; Transcription, Genetic
PubMed: 11891195
DOI: 10.1016/S0002-9440(10)64919-X