scholarly journals Predicted Drosophila Interactome Resource and web tool for functional interpretation of differentially expressed genes

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Xiao-Bao Ding ◽  
Jie Jin ◽  
Yu-Tian Tao ◽  
Wen-Ping Guo ◽  
Li Ruan ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Protein Interactions ◽  
Model Organism ◽  
Functional Gene ◽  
Gene Interactions ◽  
Web Tool ◽  
High Quality ◽  
Functional Interpretation ◽  
Gene Set ◽  
Wide Range

Abstract Drosophila melanogaster is a well-established model organism that is widely used in genetic studies. This species enjoys the availability of a wide range of research tools, well-annotated reference databases and highly similar gene circuitry to other insects. To facilitate molecular mechanism studies in Drosophila, we present the Predicted Drosophila Interactome Resource (PDIR), a database of high-quality predicted functional gene interactions. These interactions were inferred from evidence in 10 public databases providing information for functional gene interactions from diverse perspectives. The current version of PDIR includes 102 835 putative functional associations with balanced sensitivity and specificity, which are expected to cover 22.56% of all Drosophila protein interactions. This set of functional interactions is a good reference for hypothesis formulation in molecular mechanism studies. At the same time, these interactions also serve as a high-quality reference interactome for gene set linkage analysis (GSLA), which is a web tool for the interpretation of the potential functional impacts of a set of changed genes observed in transcriptomics analyses. In a case study, we show that the PDIR/GSLA system was able to produce a more comprehensive and concise interpretation of the collective functional impact of multiple simultaneously changed genes compared with the widely used gene set annotation tools, including PANTHER and David. PDIR and its associated GSLA service can be accessed at http://drosophila.biomedtzc.cn.

scholarly journals Predicted functional interactome of Caenorhabditis elegans and a web tool for the functional interpretation of differentially expressed genes

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Peng-Cheng Chen ◽  
Li Ruan ◽  
Jie Jin ◽  
Yu-Tian Tao ◽  
Xiao-Bao Ding ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Differentially Expressed Genes ◽  
Protein Interactions ◽  
Differentially Expressed ◽  
Web Tool ◽  
High Quality ◽  
Functional Interpretation ◽  
Gene Set ◽  
C Elegans ◽  
Functional Interactions

Abstract Background The nematode worm, Caenorhabditis elegans, is a saprophytic species that has been emerging as a standard model organism since the early 1960s. This species is useful in numerous fields, including developmental biology, neurobiology, and ageing. A high-quality comprehensive molecular interaction network is needed to facilitate molecular mechanism studies in C. elegans. Results We present the predicted functional interactome of Caenorhabditis elegans (FIC), which integrates functional association data from 10 public databases to infer functional gene interactions on diverse functional perspectives. In this work, FIC includes 108,550 putative functional associations with balanced sensitivity and specificity, which are expected to cover 21.42% of all C. elegans protein interactions, and 29.25% of these associations may represent protein interactions. Based on FIC, we developed a gene set linkage analysis (GSLA) web tool to interpret potential functional impacts from a set of differentially expressed genes observed in transcriptome analyses. Conclusion We present the predicted C. elegans interactome database FIC, which is a high-quality database of predicted functional interactions among genes. The functional interactions in FIC serve as a good reference interactome for GSLA to annotate differentially expressed genes for their potential functional impacts. In a case study, the FIC/GSLA system shows more comprehensive and concise annotations compared to other widely used gene set annotation tools, including PANTHER and DAVID. FIC and its associated GSLA are available at the website http://worm.biomedtzc.cn.

scholarly journals HIR V2: a human interactome resource for the biological interpretation of differentially expressed genes via gene set linkage analysis

2020 ◽  
Author(s):  
Yu-Tian Tao ◽  
Xiao-Bao Ding ◽  
Jie Jin ◽  
Hai-bo Zhang ◽  
Qiao-lei Yang ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Protein Interactions ◽  
Biological Significance ◽  
High Quality ◽  
Human Interactome ◽  
Gene Set ◽  
Human Genes ◽  
Protein Interactome ◽  
Biological Interpretation ◽  
Transcriptomic Changes

Abstract Background To facilitate biomedical studies of disease mechanisms, a high-quality interactome that connects functionally related genes is needed to help investigators formulate pathway hypotheses and to interpret the biological logic of a phenotype at the biological process level. Results Interactions in the updated version of the human interactome resource (HIR V2) were inferred from 36 mathematical characterizations of 6 types of data that suggest functional associations between genes. This update of the HIR consists of 88,069 pairs of genes representing functional associations that are of strengths similar to those between well-studied protein interactions. Among these functional interactions, 57.04% may represent protein interactions, which are expected to cover 32.48% of the true human protein interactome. The gene set linkage analysis (GSLA) tool is developed based on the high-quality HIR V2 to identify the potential functional impacts of observed transcriptomic changes, helping to elucidate their biological significance and complementing the currently widely used enrichment-based gene set interpretation tools. Conclusions We present the HIR V2, a high-quality functional interactome of human genes, along with the gene set linkage analysis (GSLA) webtool, which utilizes the HIR V2 to interpret the biological significance of transcriptionally changed genes. A case study shows that the annotations reported by the HIR V2/GSLA system are more comprehensive and concise compared to those obtained by widely used gene set annotation tools such as PANTHER and DAVID. The HIR V2 and GSLA are available at http://human.biomedtzc.cn .

scholarly journals Genome sequencing of the neotype strain CBS 554.65 reveals the MAT1-2 locus of Aspergillus niger

2021 ◽  
Author(s):  
Valeria Ellena ◽  
Sjoerd J. Seekles ◽  
Arthur F.J. Ram ◽  
Matthias G. Steiger
Keyword(s):  
Aspergillus Niger ◽  
Genome Sequence ◽  
Model Organism ◽  
Nuclear Genome ◽  
Fungal Species ◽  
Cell Factory ◽  
Dna Assembly ◽  
High Quality ◽  
Genetic Organization ◽  
Wide Range

Abstract Background Aspergillus niger is a ubiquitous filamentous fungus widely employed as a cell factory thanks to its abilities to produce a wide range of organic acids and enzymes. Due to its economic importance and its role as model organism to study fungal fermentation, its genome was one of the first Aspergillus genomes to be sequenced in 2007. Nowadays, the genome sequences of at least five other A. niger strains are available. These, however, do not include the neotype strain CBS 554.65. Results In this study, the genome of CBS 554.65 was sequenced with PacBio. A high-quality nuclear genome sequence consisting of 17 contigs with a N50 value of 4.07 Mbp was obtained. The sequencing covered all the 8 centromeric regions of the chromosomes. In addition, a complete circular mitochondrial DNA assembly was obtained. In silico analyses revealed the presence of a MAT1-2-1 gene in this genome, contrary to the so far sequenced A. niger strains, which all contain a MAT1-1-1 gene. An alignment at the MAT locus showed a different position of the MAT1-1-1 gene of ATCC 1015 compared to the MAT1-2-1 gene of CBS 554.65, relative to the surrounding genes. In addition, 24 other sequenced isolates of A. niger showed a 1:1 ratio of MAT1-1 and MAT1-2 loci. While the genetic organization of the MAT1-2 locus of CBS 554.65 is similar to what is found in other aspergilli, the genetic organization of the MAT1-1 locus is flipped in all sequenced strains. Conclusions This study, besides providing a high-quality genome sequence of an important A. niger strain, suggests the occurrence of genetic flipping or switching events at the MAT1-1 locus of A. niger. These results provide new insights in the mating system of A. niger and could contribute to the investigation and potential discovery of sexuality of this so far asexual fungal species.

scholarly journals Association between a Prognostic Gene Signature and Functional Gene Sets

2008 ◽  
Vol 2 ◽  
pp. BBI.S1018 ◽  
Author(s):  
Manuela Hummel ◽  
Klaus H. Metzeler ◽  
Christian Buske ◽  
Stefan K. Bohlander ◽  
Ulrich Mansmann
Keyword(s):  
Gene Ontology ◽  
Risk Score ◽  
Gene Signature ◽  
Functional Gene ◽  
Gene Set Enrichment ◽  
Functional Interpretation ◽  
Data Set ◽  
Gene Set ◽  
Signature Genes ◽  
Gene Sets

Background The development of expression-based gene signatures for predicting prognosis or class membership is a popular and challenging task. Besides their stringent validation, signatures need a functional interpretation and must be placed in a biological context. Popular tools such as Gene Set Enrichment have drawbacks because they are restricted to annotated genes and are unable to capture the information hidden in the signature's non-annotated genes. Methodology We propose concepts to relate a signature with functional gene sets like pathways or Gene Ontology categories. The connection between single signature genes and a specific pathway is explored by hierarchical variable selection and gene association networks. The risk score derived from an individual patient's signature is related to expression patterns of pathways and Gene Ontology categories. Global tests are useful for these tasks, and they adjust for other factors. GlobalAncova is used to explore the effect on gene expression in specific functional groups from the interaction of the score and selected mutations in the patient's genome. Results We apply the proposed methods to an expression data set and a corresponding gene signature for predicting survival in Acute Myeloid Leukemia (AML). The example demonstrates strong relations between the signature and cancer-related pathways. The signature-based risk score was found to be associated with development-related biological processes. Conclusions Many authors interpret the functional aspects of a gene signature by linking signature genes to pathways or relevant functional gene groups. The method of gene set enrichment is preferred to annotating signature genes to specific Gene Ontology categories. The strategies proposed in this paper go beyond the restriction of annotation and deepen the insights into the biological mechanisms reflected in the information given by a signature.

scholarly journals How to develop objective-driven comprehensive science outreach initiatives aiming at multiple audiences

2015 ◽  
Author(s):  
Sanjai Patel ◽  
Andreas Prokop
Keyword(s):  
Extracurricular Activities ◽  
Public Awareness ◽  
Model Organism ◽  
Added Value ◽  
High Quality ◽  
Science Outreach ◽  
Time Saving ◽  
The Public ◽  
Wide Range ◽  
Multiple Audiences

Science outreach has become increasingly important for researchers and needs to be of ever improving quality, although the time available aside our science, teaching and administration activities is steadily decreasing. To square this circle, effective strategies are required. Here we argue that this can be achieved by setting simple but ambitious overarching objectives for comprehensive outreach initiatives which target multiple audiences, supported by cumulative build-up of shared high-quality resources, as well as the exchange and collaboration amongst scientists with a common outreach aim. To exemplify this strategy, we explain the low-budget, yet high-quality outreach initiative of the Manchester Fly Facility which aims to promote public awareness of the importance of the model organism Drosophila for biomedical research. (1) This initiative targets the general public at science fairs, through public videos, or through extracurricular activities in schools as well as the development of curriculum-relevant sample lessons for teachers - all supported by a dedicated website. (2) The initiative targets university students: by adapting the public outreach resources for their teaching, and through newly developed advanced training strategies that amalgamate the outreach objectives. (3) It targets fellow scientists through blogs, conference presentations and a second website that provides a one-stop-shop for resources, arguments and strategies. As will be explained, this multi-pronged approach is time-saving in the long run and it is powerful because it reaches a wide range of audiences, helps to gain momentum, to build resource, and to gradually improve quality through cross-fertilisation between different activities, and through exchange within the science community. This helps to build communities, and high-quality outreach will have further important added value: arguments that impress the public, tend to be most effective also with reviewers and grant panel members, and often help to readjust aspects of your own scientific work.

scholarly journals Genome sequencing of the neotype strain CBS 554.65 reveals the MAT1–2 locus of Aspergillus niger

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Valeria Ellena ◽  
Sjoerd J. Seekles ◽  
Gabriel A. Vignolle ◽  
Arthur F. J. Ram ◽  
Matthias G. Steiger
Keyword(s):  
Aspergillus Niger ◽  
Genome Sequence ◽  
Model Organism ◽  
Nuclear Genome ◽  
Cell Factory ◽  
Dna Assembly ◽  
High Quality ◽  
Wide Range ◽  
Conserved Genes ◽  
A Cell

Abstract Background Aspergillus niger is a ubiquitous filamentous fungus widely employed as a cell factory thanks to its abilities to produce a wide range of organic acids and enzymes. Its genome was one of the first Aspergillus genomes to be sequenced in 2007, due to its economic importance and its role as model organism to study fungal fermentation. Nowadays, the genome sequences of more than 20 A. niger strains are available. These, however, do not include the neotype strain CBS 554.65. Results The genome of CBS 554.65 was sequenced with PacBio. A high-quality nuclear genome sequence consisting of 17 contigs with a N50 value of 4.07 Mbp was obtained. The assembly covered all the 8 centromeric regions of the chromosomes. In addition, a complete circular mitochondrial DNA assembly was obtained. Bioinformatic analyses revealed the presence of a MAT1-2-1 gene in this genome, contrary to the most commonly used A. niger strains, such as ATCC 1015 and CBS 513.88, which contain a MAT1-1-1 gene. A nucleotide alignment showed a different orientation of the MAT1–1 locus of ATCC 1015 compared to the MAT1–2 locus of CBS 554.65, relative to conserved genes flanking the MAT locus. Within 24 newly sequenced isolates of A. niger half of them had a MAT1–1 locus and the other half a MAT1–2 locus. The genomic organization of the MAT1–2 locus in CBS 554.65 is similar to other Aspergillus species. In contrast, the region comprising the MAT1–1 locus is flipped in all sequenced strains of A. niger. Conclusions This study, besides providing a high-quality genome sequence of an important A. niger strain, suggests the occurrence of genetic flipping or switching events at the MAT1–1 locus of A. niger. These results provide new insights in the mating system of A. niger and could contribute to the investigation and potential discovery of sexuality in this species long thought to be asexual.

AMPCOLOY 570

Alloy Digest ◽  
1980 ◽  
Vol 29 (3) ◽  
Keyword(s):  
Corrosion Resistance ◽  
Cast Iron ◽  
Iron Alloy ◽  
Heat Treating ◽  
Nickel Aluminum ◽  
High Quality ◽  
Glass Making ◽  
Temperature Performance ◽  
Wide Range ◽  
Cobalt Iron

Abstract AMPCOLOY 570 is a cast copper-nickel-aluminum-cobalt-iron alloy specially developed for applications involving severe stresses and high temperatures, such as glass-making molds and plate-glass rolls. It is significantly superior to cast iron which has been commonly used for glass-making molds. Good foundry techniques will yield high-quality castings of Ampcoloy 570 in a wide range of section sizes. This datasheet provides information on composition, physical properties, hardness, elasticity, and tensile properties. It also includes information on high temperature performance and corrosion resistance as well as casting, heat treating, machining, and joining. Filing Code: Cu-392. Producer or source: Ampco Metal Inc..

Current Trends in Biotherapeutic Higher Order Structure Characterization by Irreversible Covalent Footprinting Mass Spectrometry

2019 ◽  
Vol 26 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Natalie K. Garcia ◽  
Galahad Deperalta ◽  
Aaron T. Wecksler
Keyword(s):  
Mass Spectrometry ◽  
Protein Structure ◽  
Protein Interactions ◽  
Quaternary Structure ◽  
Solvent Accessibility ◽  
Higher Order ◽  
Structure Characterization ◽  
Order Structure ◽  
Protein Footprinting ◽  
Wide Range

Background: Biotherapeutics, particularly monoclonal antibodies (mAbs), are a maturing class of drugs capable of treating a wide range of diseases. Therapeutic function and solutionstability are linked to the proper three-dimensional organization of the primary sequence into Higher Order Structure (HOS) as well as the timescales of protein motions (dynamics). Methods that directly monitor protein HOS and dynamics are important for mapping therapeutically relevant protein-protein interactions and assessing properly folded structures. Irreversible covalent protein footprinting Mass Spectrometry (MS) tools, such as site-specific amino acid labeling and hydroxyl radical footprinting are analytical techniques capable of monitoring the side chain solvent accessibility influenced by tertiary and quaternary structure. Here we discuss the methodology, examples of biotherapeutic applications, and the future directions of irreversible covalent protein footprinting MS in biotherapeutic research and development. Conclusion: Bottom-up mass spectrometry using irreversible labeling techniques provide valuable information for characterizing solution-phase protein structure. Examples range from epitope mapping and protein-ligand interactions, to probing challenging structures of membrane proteins. By paring these techniques with hydrogen-deuterium exchange, spectroscopic analysis, or static-phase structural data such as crystallography or electron microscopy, a comprehensive understanding of protein structure can be obtained.

Approach in improving potency and selectivity of kinase inhibitors: Allosteric kinase inhibitors

2020 ◽  
Vol 21 ◽  
Author(s):  
Shangfei Wei ◽  
Tianming Zhao ◽  
Jie Wang ◽  
Xin Zhai
Keyword(s):  
Protein Interactions ◽  
Kinase Inhibitors ◽  
Binding Modes ◽  
Allosteric Inhibitors ◽  
Wide Range ◽  
Allosteric Sites ◽  
Protein Functions ◽  
Regulate Protein

: Allostery is an efficient and particular regulatory mechanism to regulate protein functions. Different from conserved orthosteric sites, allosteric sites have distinctive functional mechanism to form the complex regulatory network. In drug discovery, kinase inhibitors targeting the allosteric pockets have received extensive attention for the advantages of high selectivity and low toxicity. The approval of trametinib as the first allosteric inhibitor validated that allosteric inhibitors could be used as effective therapeutic drugs for treatment of diseases. To date, a wide range of allosteric inhibitors have been identified. In this perspective, we outline different binding modes and potential advantages of allosteric inhibitors. In the meantime, the research processes of typical and novel allosteric inhibitors are described briefly in terms of structureactivity relationships, ligand-protein interactions and in vitro and in vivo activity. Additionally, challenges as well as opportunities are presented.

Utilizing Cancer - Functional Gene Set - Compound Networks to Identify Putative Drugs for Breast Cancer

2018 ◽  
Vol 21 (2) ◽  
pp. 74-83
Author(s):  
Tzu-Hung Hsiao ◽  
Yu-Chiao Chiu ◽  
Yu-Heng Chen ◽  
Yu-Ching Hsu ◽  
Hung-I Harry Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Cancer Survival ◽  
Expression Profiles ◽  
Functional Gene ◽  
Gene Set Enrichment Analysis ◽  
Gene Set ◽  
Gene Sets

Aim and Objective: The number of anticancer drugs available currently is limited, and some of them have low treatment response rates. Moreover, developing a new drug for cancer therapy is labor intensive and sometimes cost prohibitive. Therefore, “repositioning” of known cancer treatment compounds can speed up the development time and potentially increase the response rate of cancer therapy. This study proposes a systems biology method for identifying new compound candidates for cancer treatment in two separate procedures. Materials and Methods: First, a “gene set–compound” network was constructed by conducting gene set enrichment analysis on the expression profile of responses to a compound. Second, survival analyses were applied to gene expression profiles derived from four breast cancer patient cohorts to identify gene sets that are associated with cancer survival. A “cancer–functional gene set– compound” network was constructed, and candidate anticancer compounds were identified. Through the use of breast cancer as an example, 162 breast cancer survival-associated gene sets and 172 putative compounds were obtained. Results: We demonstrated how to utilize the clinical relevance of previous studies through gene sets and then connect it to candidate compounds by using gene expression data from the Connectivity Map. Specifically, we chose a gene set derived from a stem cell study to demonstrate its association with breast cancer prognosis and discussed six new compounds that can increase the expression of the gene set after the treatment. Conclusion: Our method can effectively identify compounds with a potential to be “repositioned” for cancer treatment according to their active mechanisms and their association with patients’ survival time.

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