Use of a combined antibacterial synergy approach and the ANNOgesic tool to identify novel targets within the gene networks of multidrug-resistant .

Since the 1980s, the development of new drug classes for the treatment of multidrug-resistant has become limited, highlighting the urgent need for novel antibiotics. To address this challenge, this study aimed to explore the synergistic interactions between chemical compounds and representative antibiotics, such as carbapenem and colistin. The primary objective of this study was not only to mitigate the adverse impact of multidrug-resistant on public health but also to establish a sustainable balance among humans, animals, and the environment.

WNT5A drives interleukin-6-dependent epithelial-mesenchymal transition via the JAK/STAT pathway in keloid pathogenesis.

Background: Keloid scarring is a fibroproliferative disease caused by aberrant genetic activation with an unclear underlying mechanism. Genetic predisposition, aberrant cellular responses to environmental factors, increased inflammatory cytokines and epithelial-mesenchymal transition (EMT) phenomena are known as major contributors. In this study, we aimed to identify the molecular drivers that initiate keloid pathogenesis.

RNA sequencing and bioinformatics analysis revealed PACSIN3 as a potential novel biomarker for platinum resistance in epithelial ovarian cancer.

Background: Failure to respond to treatment in epithelial ovarian cancer can often be attributed to platinum-based chemotherapy resistance. However, the possible mechanisms or candidate biomarkers associated with platinum resistance are yet to be elucidated, even though many researchers have performed related studies.

Methods: We performed RNA sequencing of clinical specimens obtained from patients with platinum-sensitive or resistant epithelial ovarian cancer (EOC).

Relationship between Egg Consumption and Body Composition as Well as Serum Cholesterol Level: Korea National Health and Nutrition Examination Survey 2008-2011.

We analyzed the relationship between egg consumption, body composition, and serum cholesterol levels. We obtained data on egg consumption by using a food frequency questionnaire (FFQ) (13,132 adults) and the 24-h dietary recall (24HR) (13,366 adults) from the fourth and fifth Korea National Health and Nutrition Examination Surveys (2008-2011). In men, consuming 2-3 eggs/week was associated with higher fat mass (FM), percentage body fat (PBF), and fat-to-muscle ratio (FtoM), compared to consuming <1 egg/week.

Construction of Functional Protein Networks Using Domain Profile Associations.

Proteins are major functional molecules that physically and functionally interact to carry out cellular processes. The physical interactions are generally mediated by domain-level interactions. Thus, novel protein-protein interactions can be predicted using various computational methods based on domain-domain interactions, using resolved structures of protein complexes.

Pathway-specific protein domains are predictive for human diseases.

Protein domains are basic functional units of proteins. Many protein domains are pervasive among diverse biological processes, yet some are associated with specific pathways. Human complex diseases are generally viewed as pathway-level disorders.

Evaluation of an Automated Screening Assay, Compared to Indirect Immunofluorescence, an Extractable Nuclear Antigen Assay, and a Line Immunoassay in a Large Cohort of Asian Patients with Antinuclear Antibody-Associated Rheumatoid Diseases: A Multicenter Retrospective Study.

We assessed the diagnostic utility of the connective tissue disease (CTD) screen as an automated screening test, in comparison with the indirect immunofluorescence (IIF), EliA extractable nuclear antigen (ENA), and line immunoassay (LIA) for patients with antinuclear antibody- (ANA-) associated rheumatoid disease (AARD). A total of 1115 serum samples from two university hospitals were assayed using these four autoantibody-based methods. The AARD group consisted of patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), and mixed connective tissue disease (MCTD).

GWAB: a web server for the network-based boosting of human genome-wide association data.

During the last decade, genome-wide association studies (GWAS) have represented a major approach to dissect complex human genetic diseases. Due in part to limited statistical power, most studies identify only small numbers of candidate genes that pass the conventional significance thresholds (e.g.

From sequencing data to gene functions: co-functional network approaches.

Advanced high-throughput sequencing technology accumulated massive amount of genomics and transcriptomics data in the public databases. Due to the high technical accessibility, DNA and RNA sequencing have huge potential for the study of gene functions in most species including animals and crops. A proven analytic platform to convert sequencing data to gene functional information is co-functional network.

MUFFINN: cancer gene discovery via network analysis of somatic mutation data.

A major challenge for distinguishing cancer-causing driver mutations from inconsequential passenger mutations is the long-tail of infrequently mutated genes in cancer genomes. Here, we present and evaluate a method for prioritizing cancer genes accounting not only for mutations in individual genes but also in their neighbors in functional networks, MUFFINN (MUtations For Functional Impact on Network Neighbors). This pathway-centric method shows high sensitivity compared with gene-centric analyses of mutation data.

Weighted mutual information analysis substantially improves domain-based functional network models.

Motivation: Functional protein-protein interaction (PPI) networks elucidate molecular pathways underlying complex phenotypes, including those of human diseases. Extrapolation of domain-domain interactions (DDIs) from known PPIs is a major domain-based method for inferring functional PPI networks. However, the protein domain is a functional unit of the protein.

Pathway-Dependent Effectiveness of Network Algorithms for Gene Prioritization.

A network-based approach has proven useful for the identification of novel genes associated with complex phenotypes, including human diseases. Because network-based gene prioritization algorithms are based on propagating information of known phenotype-associated genes through networks, the pathway structure of each phenotype might significantly affect the effectiveness of algorithms. We systematically compared two popular network algorithms with distinct mechanisms--direct neighborhood which propagates information to only direct network neighbors, and network diffusion which diffuses information throughout the entire network--in prioritization of genes for worm and human phenotypes.

TRRUST: a reference database of human transcriptional regulatory interactions.

The reconstruction of transcriptional regulatory networks (TRNs) is a long-standing challenge in human genetics. Numerous computational methods have been developed to infer regulatory interactions between human transcriptional factors (TFs) and target genes from high-throughput data, and their performance evaluation requires gold-standard interactions. Here we present a database of literature-curated human TF-target interactions, TRRUST (transcriptional regulatory relationships unravelled by sentence-based text-mining, http://www.

FlyNet: a versatile network prioritization server for the Drosophila community.

Drosophila melanogaster (fruit fly) has been a popular model organism in animal genetics due to the high accessibility of reverse-genetics tools. In addition, the close relationship between the Drosophila and human genomes rationalizes the use of Drosophila as an invertebrate model for human neurobiology and disease research. A platform technology for predicting candidate genes or functions would further enhance the usefulness of this long-established model organism for gene-to-phenotype mapping.

RiceNet v2: an improved network prioritization server for rice genes.

Rice is the most important staple food crop and a model grass for studies of bioenergy crops. We previously published a genome-scale functional network server called RiceNet, constructed by integrating diverse genomics data and demonstrated the use of the network in genetic dissection of rice biotic stress responses and its usefulness for other grass species. Since the initial construction of the network, there has been a significant increase in the amount of publicly available rice genomics data.

Network-assisted genetic dissection of pathogenicity and drug resistance in the opportunistic human pathogenic fungus Cryptococcus neoformans.

Cryptococcus neoformans is an opportunistic human pathogenic fungus that causes meningoencephalitis. Due to the increasing global risk of cryptococcosis and the emergence of drug-resistant strains, the development of predictive genetics platforms for the rapid identification of novel genes governing pathogenicity and drug resistance of C. neoformans is imperative.

EcoliNet: a database of cofunctional gene network for Escherichia coli.

During the past several decades, Escherichia coli has been a treasure chest for molecular biology. The molecular mechanisms of many fundamental cellular processes have been discovered through research on this bacterium. Although much basic research now focuses on more complex model organisms, E.

AraNet v2: an improved database of co-functional gene networks for the study of Arabidopsis thaliana and 27 other nonmodel plant species.

Arabidopsis thaliana is a reference plant that has been studied intensively for several decades. Recent advances in high-throughput experimental technology have enabled the generation of an unprecedented amount of data from A. thaliana, which has facilitated data-driven approaches to unravel the genetic organization of plant phenotypes.

YeastNet v3: a public database of data-specific and integrated functional gene networks for Saccharomyces cerevisiae.

Saccharomyces cerevisiae, i.e. baker's yeast, is a widely studied model organism in eukaryote genetics because of its simple protocols for genetic manipulation and phenotype profiling.

Prioritizing candidate disease genes by network-based boosting of genome-wide association data.

Network "guilt by association" (GBA) is a proven approach for identifying novel disease genes based on the observation that similar mutational phenotypes arise from functionally related genes. In principle, this approach could account even for nonadditive genetic interactions, which underlie the synergistic combinations of mutations often linked to complex diseases. Here, we analyze a large-scale, human gene functional interaction network (dubbed HumanNet).

Exception discovery: a novel method for the identification of differentially expressed proteins.

The identification of differentially expressed proteins (DEPs) observed under specific conditions is one of the key issues in proteomics research. There are currently several ways to detect the changes of a specific protein's expression level in two-dimensional electrophoresis (2-DE) gel images such as statistical analysis and graphical visualization. However, it is quite difficult to handle the information of an individual protein manually by these methods due to the large distortions of patterns in 2-DE images.

A landmark extraction method for protein 2DE gel images based on multi-dimensional clustering.

Objective: Two-dimensional electrophoresis (2DE) is a separation technique that can identify target proteins existing in a tissue. Its result is represented by a gel image that displays an individual protein in a tissue as a spot. However, because the technique suffers from low reproducibility, a user should manually annotate landmark spots on each gel image to analyze the spots of different images together.

A potential role for cx43-hemichannels in staurosporin-induced apoptosis.

To address the role of gap junction hemichannels in apoptosis, the cell death induced by staurosporine (ST) was evaluated in wild type HeLa cells (HeLa-WT) and transfectants expressing either full-length connexin43 (HeLa-Cx43) or a C-terminal truncation of Cx43 (HeLa-DeltaCT). Cell death was measured with fluorescence-activated cell sorting (FACS), both DNA and nuclear fragmentation methods and assays for PARP and caspase 3. The ST-mediated cell death was accelerated in HeLa-Cx43 cells compared to HeLa-WT and HeLa-DeltaCT.