Evolutionary algorithms (EAs), as global search methods, are proved to be more robust than their counterpart local heuristics for detecting protein complexes in protein-protein interaction (PPI) networks. Typically, the source of robustness of these EAs comes from their components and parameters. These components are solution representation, selection, crossover, and mutation. Unfortunately, almost all EA based complex detection methods suggested in the literature were designed with only canonical or traditional components. Further, topological structure of the protein network is the main information that is used in the design of almost all such components. The main contribution of this paper is to formulate a more robust EA with more biological consistency. For this purpose, a new crossover operator is suggested where biological information in terms of both gene semantic similarity and protein functional similarity is fed into its design. To reflect the heuristic roles of both semantic and functional similarities, this paper introduces two gene ontology (GO) aware crossover operators. These are direct annotation-aware and inherited annotation-aware crossover operators. The first strategy is handled with the direct gene ontology annotation of the proteins, while the second strategy is handled with the directed acyclic graph (DAG) of each gene ontology term in the gene product. To conduct our experiments, the proposed EAs with GO-aware crossover operators are compared against the state-of-the-art heuristic, canonical EAs with the traditional crossover operator, and GO-based EAs. Simulation results are evaluated in terms of recall, precision, and F measure at both complex level and protein level. The results prove that the new EA design encourages a more reliable treatment of exploration and exploitation and, thus, improves the detection ability for more accurate protein complex structures.
Protein arginine methyltransferases (PRMTs) play important roles in transcription, splicing, DNA damage repair, RNA biology, and cellular metabolism. Thus, PRMTs have been attractive targets for various diseases. In this study, we reported the design and synthesis of a potent pan-inhibitor for PRMTs that tethers a thioadenosine and various substituted guanidino groups through a propyl linker. Compound II757 exhibits a half-maximal inhibition concentration (IC50) value of 5 to 555 nM for eight tested PRMTs, with the highest inhibition for PRMT4 (IC50 = 5 nM). The kinetic study demonstrated that II757 competitively binds at the SAM binding site of PRMT1. Notably, II757 is selective for PRMTs over a panel of other methyltransferases, w
... Show MoreDespite the G protein-coupled receptors (GPCRs) being the largest family of signalling proteins at the surface of cells, their potential to be targeted in cancer therapy is still under-utilised. This review highlights the contribution of these receptors to the process of oncogenesis and points to some likely challenges that might be encountered in targeting them. GPCR-signalling pathways are often complex and can be tissue-specific. Cancer cells hijack these communication networks to their proliferative advantage. The role of selected GPCRs in the different hallmarks of cancer is examined to highlight the complexity of targeting these receptors for therapeutic benefit. Our
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Detection of virulence gene agglutinin-like sequence (ALS) 1 by using molecular technology from clinical samples (
Aim of the present study is Identification of specific gene for GPCR using specific primers .and identification of difference in PCR analysis in patients with heart thrombosis and compared with healthy, Sequencing of PCR product regarding GPCR compared for all three subject, Identification the similarity of human GPCR with local strain of yeast fifty healthy control and fifty patients with thrombosis which diagnosed medically with cardiac specific troponin t, troponin 1 levels and electro myocardiogram ECG. The aged for all subjects ranged (39-75) years patients were lying in cardiac care unit at Ibn- al- Nafees teaching hospital and Sheikh Zayed teaching hospital. Genomic DNA of whole blood was extracted from buffy coat and cell cu
... Show MoreEscherichia coli (E. coli) is a frequent gram-negative bacterium that causes nosocomial infections, affecting more than 100 million patients annually worldwide. Bacterial lipopolysaccharide (LPS) from E. coli binds to toll-like receptor 4 (TLR4) and its co-receptor’s cluster of differentiation protein 14 (CD14) and myeloid differentiation factor 2 (MD2), collectively known as the LPS receptor complex. LPCAT2 participates in lipid-raft assembly by phospholipid remodelling. Previous research has proven that LPCAT2 co-localises in lipid rafts with TLR4 and regulates macrophage inflammatory response. However, no published evidence exists of the influence of LPCAT2 on the gene expression of the LPS receptor complex induced by smooth or rough b
... Show MoreA disease of the reproductive system known as "infertility" is characterized by the inability to conceive after twelve months or more of sexual activity. This study was carried out to investigate the level of the DAZ protein in “Azoospermia” Iraqi patients. One hundred and fifty human blood samples were collected from different regions in Baghdad governorate include (private medicals Labs and “high institute for infertility diagnosis” assisted reproductive techniques and Kamal Al- Samara'ay IVF Hospital). The control group (fertile) consists of 50 males with an age range between 22-51 years old, while the patient (infertile group) consists of 100 sample males with ages ranging between 25-51 years old. The correlation of mean age for
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