Dataset Information

HumanNet v2: human gene networks for disease research.

ABSTRACT: Human gene networks have proven useful in many aspects of disease research, with numerous network-based strategies developed for generating hypotheses about gene-disease-drug associations. The ability to predict and organize genes most relevant to a specific disease has proven especially important. We previously developed a human functional gene network, HumanNet, by integrating diverse types of omics data using Bayesian statistics framework and demonstrated its ability to retrieve disease genes. Here, we present HumanNet v2 (http://www.inetbio.org/humannet), a database of human gene networks, which was updated by incorporating new data types, extending data sources and improving network inference algorithms. HumanNet now comprises a hierarchy of human gene networks, allowing for more flexible incorporation of network information into studies. HumanNet performs well in ranking disease-linked gene sets with minimal literature-dependent biases. We observe that incorporating model organisms' protein-protein interactions does not markedly improve disease gene predictions, suggesting that many of the disease gene associations are now captured directly in human-derived datasets. With an improved interactive user interface for disease network analysis, we expect HumanNet will be a useful resource for network medicine.

SUBMITTER: Hwang S

PROVIDER: S-EPMC6323914 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

HumanNet v2: human gene networks for disease research.

Hwang Sohyun S Kim Chan Yeong CY Yang Sunmo S Kim Eiru E Hart Traver T Marcotte Edward M EM Lee Insuk I

Nucleic acids research 20190101 D1

Human gene networks have proven useful in many aspects of disease research, with numerous network-based strategies developed for generating hypotheses about gene-disease-drug associations. The ability to predict and organize genes most relevant to a specific disease has proven especially important. We previously developed a human functional gene network, HumanNet, by integrating diverse types of omics data using Bayesian statistics framework and demonstrated its ability to retrieve disease genes ...[more]

PMID: 30418591

Similar Datasets

Project description:We are entering the era of personalized medicine in which an individual's genetic makeup will eventually determine how a doctor can tailor his or her therapy. Therefore, it is becoming critical to understand the genetic basis of common diseases, for example, which genes predispose and rare genetic variants contribute to diseases, and so on. Our study focuses on helping researchers, medical practitioners, and pharmacists in having a broad view of genetic variants that may be implicated in the likelihood of developing certain diseases. Our focus here is to create a comprehensive database with mobile access to all available, authentic and actionable genes, SNPs, and classified diseases and drugs collected from different clinical and genomics databases worldwide, including Ensembl, GenCode, ClinVar, GeneCards, DISEASES, HGMD, OMIM, GTR, CNVD, Novoseek, Swiss-Prot, LncRNADisease, Orphanet, GWAS Catalog, SwissVar, COSMIC, WHO, and FDA. We present a new cutting-edge gene-SNP-disease-drug mobile database with a smart phone application, integrating information about classified diseases and related genes, germline and somatic mutations, and drugs. Its database includes over 59 000 protein-coding and noncoding genes; over 67 000 germline SNPs and over a million somatic mutations reported for over 19 000 protein-coding genes located in over 1000 regions, published with over 3000 articles in over 415 journals available at the PUBMED; over 80 000 ICDs; over 123 000 NDCs; and over 100 000 classified gene-SNP-disease associations. We present an application that can provide new insights into the information about genetic basis of human complex diseases and contribute to assimilating genomic with phenotypic data for the availability of gene-based designer drugs, precise targeting of molecular fingerprints for tumor, appropriate drug therapy, predicting individual susceptibility to disease, diagnosis, and treatment of rare illnesses are all a few of the many transformations expected in the decade to come.

Project description:BACKGROUND: We have recently shown by formally modelling human protein interaction networks (PINs) as metric spaces and classified proteins into zones based on their distance from the topological centre that hub proteins are primarily centrally located. We also showed that zones closest to the network centre are enriched for critically important proteins and are also functionally very specialised for specific 'house keeping' functions. We proposed that proteins closest to the network centre may present good therapeutic targets. Here, we present multiple pieces of novel functional evidence that provides strong support for this hypothesis. RESULTS: We found that the human PINs has a highly connected signalling core, with the majority of proteins involved in signalling located in the two zones closest to the topological centre. The majority of essential, disease related, tumour suppressor, oncogenic and approved drug target proteins were found to be centrally located. Similarly, the majority of proteins consistently expressed in 13 types of cancer are also predominantly located in zones closest to the centre. Proteins from zones 1 and 2 were also found to comprise the majority of proteins in key KEGG pathways such as MAPK-signalling, the cell cycle, apoptosis and also pathways in cancer, with very similar patterns seen in pathways that lead to cancers such as melanoma and glioma, and non-neoplastic diseases such as measles, inflammatory bowel disease and Alzheimer's disease. CONCLUSIONS: Based on the diversity of evidence uncovered, we propose that when considered holistically, proteins located centrally in the human PINs that also have similar functions to existing drug targets are good candidate targets for novel therapeutics. Similarly, since disease pathways are dominated by centrally located proteins, candidates shortlisted in genome scale disease studies can be further prioritized and contextualised based on whether they occupy central positions in the human PINs.

Project description:Inflammatory bowel disease (IBD) is a long-term inflammatory immune-mediated gut illness with several extra-intestinal complications. The aims of this study were to identify a novel network-based meta-analysis approach on the basis of the combinations of the differentially expressed genes (DEGs) from microarray data, to enrich the functional modules from human protein-protein interaction (PPI) and gene ontology (GO) data, and to profile the ncRNAs on the genes involved in IBD. The gene expression profiles of GSE126124, GSE87473, GSE75214, and GSE95095 are obtained from the Gene Expression Omnibus (GEO) database based on the study criteria between 2017 and 2022. The DEGs were screened by the R software. DEGs were then used to examine gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The ncRNAs including the miRNAs and ceRNAs were predicted on the PPIs visualized using Cytoscape. Enrichment analysis of genes with differential expression (n = 342) using KEGG and GO showed that the signaling pathways related with staphylococcus aureus and pertussis bacterial infections may stimulate the immune system and exacerbate IBD via the interaction with human proteins including Fibrinogen gamma chain (FGG), Keratin 10 (KRT10), and Toll like receptor 4 (TLR4). By building a ceRNA network, lncRNA XIST and NEAT1 were determined by affecting common miRNAs, hsa-miR-6875-5p, hsa-miR-1908-5p, hsa-miR-186-5p, hsa-miR-6763-5p, hsa-miR-4436a, and hsa-miR-520a-5p. Additionally, the chromosome regions including NM_001039703 and NM_006267, which produce the most potent circRNAs play a significant role in the ceRNA network of IBD. Also, we predicted the siRNAs that would be most effective against the bacterial genes in staphylococcus aureus and pertussis infections. These findings suggested that three genes (FGG, KRT10, and TLR4), six miRNAs (hsa-miR-6875-5p, hsa-miR-1908-5p, hsa-miR-186-5p, hsa-miR-4436a, hsa-miR-520a-5p, and hsa-miR-6763-5p), two lncRNAs (XIST and NEAT1), and chromosomal regions including NM_001039703 and NM_006267 with the production of the most effective circRNAs are involved in the ncRNA-associated ceRNA network of IBD. These ncRNA profiles are related to the described gene functions and may play therapeutic targets in controlling inflammatory bowel disease.

Project description:BACKGROUNDUnderstanding the effect of human genetic variations on disease can provide insight into phenotype-genotype relationships, and has great potential for improving the effectiveness of personalized medicine. While some genetic markers linked to disease susceptibility have been identified, a large number are still unknown. In this paper, we propose a pathway-based approach to extend disease-variant associations and find new molecular connections between genetic mutations and diseases.METHODSWe used a compilation of over 80,000 human genetic variants with known disease associations from databases including the Online Mendelian Inheritance in Man (OMIM), Clinical Variance database (ClinVar), Universal Protein Resource (UniProt), and Human Gene Mutation Database (HGMD). Furthermore, we used the Unified Medical Language System (UMLS) to normalize variant phenotype terminologies, mapping 87% of unique genetic variants to phenotypic disorder concepts. Lastly, variants were grouped by UMLS Medical Subject Heading (MeSH) identifiers to determine pathway enrichment in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.RESULTSBy linking KEGG pathways through underlying variant associations, we elucidated connections between the human genetic variant-based disease phenome and metabolic pathways, finding novel disease connections not otherwise detected through gene-level analysis. When looking at broader disease categories, our network analysis showed that large complex diseases, such as cancers, are highly linked by their common pathways. In addition, we found Cardiovascular Diseases and Skin and Connective Tissue Diseases to have the highest number of common pathways, among 35 significant main disease category (MeSH) pairings.CONCLUSIONSThis study constitutes an important contribution to extending disease-variant connections and new molecular links between diseases. Novel disease connections were made by disease-pathway associations not otherwise detected through single-gene analysis. For instance, we found that mutations in different genes associated to Noonan Syndrome and Essential Hypertension share a common pathway. This analysis also provides the foundation to build novel disease-drug networks through their underlying common metabolic pathways, thus enabling new diagnostic and therapeutic interventions.

Dataset Information

HumanNet v2: human gene networks for disease research.

Publications

HumanNet v2: human gene networks for disease research.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets