scholarly journals High-throughput analysis of B3GLCT regulation predicts phenotype of Peters' Plus Syndrome in line with the miRNA Proxy Hypothesis

2021 ◽  
Author(s):  
Chu T Thu ◽  
Jonathan Y. Chung ◽  
Deepika Dhawan ◽  
Christopher A. Vaiana ◽  
Lara K. Mahal
Keyword(s):  
High Throughput ◽  
Posttranslational Modifications ◽  
False Positive Rate ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
High Throughput Analysis ◽  
Target Network ◽  
Biological Phenotype

MicroRNAs (miRNAs, miRs) finely tune protein expression and target networks of 100s-1000s of genes that control specific biological processes. They are critical regulators of glycosylation, one of the most diverse and abundant posttranslational modifications. In recent work, miRs have been shown to predict the biological functions of glycosylation enzymes, leading to the miRNA proxy hypothesis which states, if a miR drives a specific biological phenotype, the targets of that miR will drive the same biological phenotype. Testing of this powerful hypothesis is hampered by our lack of knowledge about miR targets. Target prediction suffers from low accuracy and a high false prediction rate. Herein, we develop a high-throughput experimental platform to analyze miR:target interactions, miRFluR. We utilize this system to analyze the interactions of the entire human miRome with beta-3-glucosyltransferase (B3GLCT), a glycosylation enzyme whose loss underpins the congenital disorder Peters Plus Syndrome. Although this enzyme is predicted by multiple algorithms to be highly targeted by miRs, we identify only 27 miRs that downregulate B3GLCT, a >96% false positive rate for prediction. Functional enrichment analysis of these validated miRs predict phenotypes associated with Peters Plus Syndrome, although B3GLCT is not in their known target network. Thus, biological phenotypes driven by B3GLCT may be driven by the target networks of miRs that regulate this enzyme, providing additional evidence for the miRNA Proxy Hypothesis.

scholarly journals Understanding the Modus Operandi of MicroRNA Regulatory Clusters

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1103 ◽  
Author(s):  
Arthur C. Oliveira ◽  
Luiz A. Bovolenta ◽  
Lucas Alves ◽  
Lucas Figueiredo ◽  
Amanda O. Ribeiro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Modus Operandi ◽  
Wide Range

MicroRNAs (miRNAs) are non-coding RNAs that regulate a wide range of biological pathways by post-transcriptionally modulating gene expression levels. Given that even a single miRNA may simultaneously control several genes enrolled in multiple biological functions, one would expect that these tiny RNAs have the ability to properly sort among distinctive cellular processes to drive protein production. To test this hypothesis, we scrutinized previously published microarray datasets and clustered protein-coding gene expression profiles according to the intensity of fold-change levels caused by the exogenous transfection of 10 miRNAs (miR-1, miR-7, miR-9, miR-124, miR-128a, miR-132, miR-133a, miR-142, miR-148b, miR-181a) in a human cell line. Through an in silico functional enrichment analysis, we discovered non-randomic regulatory patterns, proper of each cluster identified. We demonstrated that miRNAs are capable of equivalently modulate the expression signatures of target genes in regulatory clusters according to the biological function they are assigned to. Moreover, target prediction analysis applied to ten vertebrate species, suggest that such miRNA regulatory modus operandi is evolutionarily conserved within vertebrates. Overall, we discovered a complex regulatory cluster-module strategy driven by miRNAs, which relies on the controlled intensity of the repression over distinct targets under specific biological contexts. Our discovery helps to clarify the mechanisms underlying the functional activity of miRNAs and makes it easier to take the fastest and most accurate path in the search for the functions of miRNAs in any distinct biological process of interest.

scholarly journals signatureSearch: environment for gene expression signature searching and functional interpretation

2020 ◽  
Vol 48 (21) ◽  
pp. e124-e124
Author(s):  
Yuzhu Duan ◽  
Daniel S Evans ◽  
Richard A Miller ◽  
Nicholas J Schork ◽  
Steven R Cummings ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Signature ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Cell Types ◽  
Functional Enrichment ◽  
Functional Interpretation ◽  
Expression Signature ◽  
Target Network ◽  
Novel Algorithms

Abstract signatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (GES) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results. In a typical GES search (GESS), a query GES is searched against a database of GESs obtained from large numbers of measurements, such as different genetic backgrounds, disease states and drug perturbations. Database matches sharing correlated signatures with the query indicate related cellular responses frequently governed by connected mechanisms, such as drugs mimicking the expression responses of a disease. To identify which processes are predominantly modulated in the GESS results, we developed specialized FEA methods combined with drug-target network visualization tools. The provided analysis tools are useful for studying the effects of genetic, chemical and environmental perturbations on biological systems, as well as searching single cell GES databases to identify novel network connections or cell types. The signatureSearch software is unique in that it provides access to an integrated environment for GESS/FEA routines that includes several novel search and enrichment methods, efficient data structures, and access to pre-built GES databases, and allowing users to work with custom databases.

Multi-label Learning for Diagnosis of Cancer and Identification of Novel Biomarkers with High-Throughput Omics

2020 ◽  
Vol 15 ◽  
Author(s):  
Shicai Liu ◽  
Hailin Tang ◽  
Hongde Liu ◽  
Jinke Wang
Keyword(s):  
High Throughput ◽  
Gastrointestinal Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Support Vector ◽  
Data Driven Approach ◽  
Diagnosis Of Cancer ◽  
Novel Biomarkers ◽  
Effective Diagnosis

Background: The advancement of bioinformatics and machine learning has facilitated the diagnosis of cancer and discovery of omics-based biomarkers. Objective: Our study employed a novel data-driven approach to classify the normal samples and different types of gastrointestinal cancer samples, to find potential biomarkers for effective diagnosis and prognosis assessment of gastrointestinal cancer patients. Methods: Different feature selection methods were used and the diagnostic performance of the proposed biosignatures was benchmarked using support vector machine (SVM) and random forest (RF) models. Results: All models showed satisfactory performance in which Multilabel-RF appeared to be the best. The accuracy of the Multilabel-RF based model was 83.12%, with precision, recall, F1 and Hamming-Loss of 79.70%, 68.31%, 0.7357 and 0.1688, respectively. Moreover, proposed biomarker signatures were highly associated with multifaceted hallmarks in cancer. Functional enrichment analysis and impact of the biomarker candidates in the prognosis of the patients were also examined. Conclusion: We successfully introduce a solid workflow based on multi-label learning with High-Throughput Omics for diagnosis of cancer and identification of novel biomarkers. Novel transcriptome biosignatures that may improve the diagnostic accuracy in gastrointestinal cancer are introduced for further validations in various clinical settings.

scholarly journals High-throughput sequence analysis reveals variation in the relative abundance of components of the bacterial and fungal microbiota in the rhizosphere of Ginkgo biloba

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8051
Author(s):  
Rujue Ruan ◽  
Zhifang Jiang ◽  
Yuhuan Wu ◽  
Maojun Xu ◽  
Jun Ni
Keyword(s):  
High Throughput ◽  
Ginkgo Biloba ◽  
High Throughput Sequencing ◽  
Sampling Site ◽  
Enrichment Analysis ◽  
Normal Growth ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Bulk Soil ◽  
Rrna Gene

Background The narrow region of soil, in contact with and directly influenced by plant roots, is called the rhizosphere. Microbes living in the rhizosphere are considered to be important factors for the normal growth and development of plants. In this research, the structural and functional diversities of microbiota between the Ginkgo biloba root rhizosphere and the corresponding bulk soil were investigated. Methods Three independent replicate sites were selected, and triplicate soil samples were collected from the rhizosphere and the bulk soil at each sampling site. The communities of bacteria and fungi were investigated using high-throughput sequencing of the 16S rRNA gene and the internal transcribed spacer (ITS) of the rRNA gene, respectively. Results A number of bacterial genera showed significantly different abundance in the rhizosphere compared to the bulk soil, including Bradyrhizobium, Rhizobium, Sphingomonas, Streptomyces and Nitrospira. Functional enrichment analysis of bacterial microbiota revealed consistently increased abundance of ATP-binding cassette (ABC) transporters and decreased abundance of two-component systems in the rhizosphere community, compared to the bulk soil community. In contrast, the situation was more complex and inconsistent for fungi, indicating the independency of the rhizosphere fungal community on the local microenvironment.

scholarly journals Bicuculline From Corydalis Species As A Natural Anti-COVID-19 Drug

2020 ◽  
pp. 1-6
Author(s):  
Shaodong Chen ◽  
Keyword(s):  
Molecular Docking ◽  
Hydrolytic Enzyme ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Literature Mining ◽  
Pathway Enrichment Analysis ◽  
Active Ingredients ◽  
Target Network

Objective: To perform molecular docking of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 3CL hydrolytic enzyme (3CLpro) and Angiotensin-Converting Enzyme II (ACE2) receptors, and to seek potential natural anti-COVID-19 drugs using computer virtual screening technology. Methods: In this study, the Autodock Vina software was first used to achieve the molecular docking of the targets, namely, sars-cov-2 3CL hydrolase and ACE2. Then, the herbals acting on 3CLpro and ACE2 receptors were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the active ingredients were also selected. After that, the chemical-target network was constructed based on the network pharmacology, and the functional enrichment analysis of Gene Ontology (GO) and the pathway enrichment analysis of Kyoto Gene and Genome Encyclopedia (KEGG) were carried out by DAVID to speculate about the mechanism of action of the core drug. Results: A total of six potential anti-COVID-19 active ingredients were selected from natural herbs. They were evaluated by the “ADME” and "Lipinski” rules and their content in the natural herbs were determined by the literature mining method. Finally, Bicuculline was selected as the anti-covid-19 candidate drug. Conclusion: Bicuculline has a stronger ability to combine with 3CLpro and ACE2 than chemical drugs recommended in the clinical practice. Internet pharmacological analysis confirms that Bicuculline can effectively resist COVID-19 pneumonia through multiple pathways.

scholarly journals Bias in miRNA enrichment analysis related to gene functional annotations

2021 ◽  
Author(s):  
Konstantinos Zagganas ◽  
Georgios K Georgakilas ◽  
Thanasis Vergoulis ◽  
Theodore Dalamagas
Keyword(s):  
Gene Annotation ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Randomization Test ◽  
Functional Enrichment ◽  
Data Sets ◽  
Analysis Tool ◽  
Statistical Measure ◽  
Rest Api

Motivation: miRNA functional enrichment is a type of analysis that is used to predict which biological functions may be affected by a group of miRNAs or validate whether a list of dysreg- ulated miRNAs are linked to a diseased state. The standard method for functional enrichment analysis uses the hypergeometric distribution to produce p-values, depicting the strength of the association between a group of miRNAs and a biological function. However, in 2015, it was shown that this approach suffers from a bias related to miRNA targets produced by target prediction algorithms and a new randomization test was proposed. Results: In this paper, we demonstrate the existence of another underlying bias which affects gene annotation data sets; additionally, we show that the statistical measure used for the estab- lished randomization test is not sensitive enough to account for it. For this reason, we propose the use of an alternative statistical measure, the "two-sided overlap", and we show that it is able to alleviate the aforementioned issue. Finally, we develop BUFET2, a miRNA enrichment analysis tool that leverages this measure (along with the old one); it is based on BUFET, a fast and scalable implementation of the established randomization test. Availability and Implementation: BUFET2 is written in C++ and is packaged with a Python wrapper script that facilitates experiment execution. Moreover, BUFET2 also comes pre-packaged in a Linux Docker image published on Docker Hub, thus eliminating the need for code compilation. Finally, BUFET2 is also publicly available to execute through a REST API. All datasets used in the experiments throught this paper are openly accessible on Zenodo (https://doi.org/10.5281/zenodo.5175819).

Systems Biology Approaches Reveal a Multi-stress Responsive WRKY Transcription Factor and Stress Associated Gene Co-expression Networks in Chickpea

2019 ◽  
Vol 14 (7) ◽  
pp. 591-601 ◽  
Author(s):  
Aravind K. Konda ◽  
Parasappa R. Sabale ◽  
Khela R. Soren ◽  
Shanmugavadivel P. Subramaniam ◽  
Pallavi Singh ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Wrky Transcription Factor ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Callose Deposition ◽  
Significant Probability

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.

scholarly journals Structural variations in papaya genomes

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenyang Liao ◽  
Xunxiao Zhang ◽  
Shengcheng Zhang ◽  
Zhicong Lin ◽  
Xingtan Zhang ◽  
...  
Keyword(s):  
Agronomic Traits ◽  
Enrichment Analysis ◽  
Copy Number Variant ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Structural Variations ◽  
Reproduction Traits ◽  
Depth Study ◽  
Environmental Adaptability ◽  
The Impact

Abstract Background Structural variations (SVs) are a type of mutations that have not been widely detected in plant genomes and studies in animals have shown their role in the process of domestication. An in-depth study of SVs will help us to further understand the impact of SVs on the phenotype and environmental adaptability during papaya domestication and provide genomic resources for the development of molecular markers. Results We detected a total of 8083 SVs, including 5260 deletions, 552 tandem duplications and 2271 insertions with deletion being the predominant, indicating the universality of deletion in the evolution of papaya genome. The distribution of these SVs is non-random in each chromosome. A total of 1794 genes overlaps with SV, of which 1350 genes are expressed in at least one tissue. The weighted correlation network analysis (WGCNA) of these expressed genes reveals co-expression relationship between SVs-genes and different tissues, and functional enrichment analysis shows their role in biological growth and environmental responses. We also identified some domesticated SVs genes related to environmental adaptability, sexual reproduction, and important agronomic traits during the domestication of papaya. Analysis of artificially selected copy number variant genes (CNV-genes) also revealed genes associated with plant growth and environmental stress. Conclusions SVs played an indispensable role in the process of papaya domestication, especially in the reproduction traits of hermaphrodite plants. The detection of genome-wide SVs and CNV-genes between cultivated gynodioecious populations and wild dioecious populations provides a reference for further understanding of the evolution process from male to hermaphrodite in papaya.

scholarly journals CCTs as new biomarkers for the prognosis of head and neck squamous cancer

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 672-688
Author(s):  
Yanbo Dong ◽  
Siyu Lu ◽  
Zhenxiao Wang ◽  
Liangfa Liu
Keyword(s):  
Head And Neck ◽  
Survival Data ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Advanced Tumor Stage ◽  
Expression Levels ◽  
T Complex ◽  
Advanced Tumor ◽  
Squamous Cancer

AbstractThe chaperonin-containing T-complex protein 1 (CCT) subunits participate in diverse diseases. However, little is known about their expression and prognostic values in human head and neck squamous cancer (HNSC). This article aims to evaluate the effects of CCT subunits regarding their prognostic values for HNSC. We mined the transcriptional and survival data of CCTs in HNSC patients from online databases. A protein–protein interaction network was constructed and a functional enrichment analysis of target genes was performed. We observed that the mRNA expression levels of CCT1/2/3/4/5/6/7/8 were higher in HNSC tissues than in normal tissues. Survival analysis revealed that the high mRNA transcriptional levels of CCT3/4/5/6/7/8 were associated with a low overall survival. The expression levels of CCT4/7 were correlated with advanced tumor stage. And the overexpression of CCT4 was associated with higher N stage of patients. Validation of CCTs’ differential expression and prognostic values was achieved by the Human Protein Atlas and GEO datasets. Mechanistic exploration of CCT subunits by the functional enrichment analysis suggests that these genes may influence the HNSC prognosis by regulating PI3K-Akt and other pathways. This study implies that CCT3/4/6/7/8 are promising biomarkers for the prognosis of HNSC.

scholarly journals Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma

2021 ◽  
Vol 28 (1) ◽  
pp. 20-33
Author(s):  
Lydia-Eirini Giannakou ◽  
Athanasios-Stefanos Giannopoulos ◽  
Chrissi Hatzoglou ◽  
Konstantinos I. Gourgoulianis ◽  
Erasmia Rouka ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Junctions ◽  
Respiratory Pathogens ◽  
Gram Negative ◽  
Human Proteins ◽  
Apoptotic Pathways

Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.

Sign in / Sign up

Export Citation Format

Share Document