HEAT: a New Tool for Gene Set Enrichment Analysis Using Comprehensive Annotation of Human Genes in H-InvDB

H-InvDB Enrichment Analysis Tool (HEAT) is a new data-mining tool for gene set enrichment analysis based on comprehensive annotations of human genes in H-InvDB. HEAT searches for H-InvDB annotations that are significantly enriched in a user-defined gene set, as compared with the entire H-InvDB representative transcripts. The advantage of HEAT is the wide variety of annotation items used for its analysis: chromosomal bands, InterPro functional domains, Gene Ontology terms, KEGG pathways, H-InvDB gene families/groups, SCOP structural domains, subcellular localization predicted by using the Wolf-PSORT program, tissue-specific gene expression as defined in the H-ANGEL database, and transcription factor binding sites in promoter regions based on JASPAR. HEAT accepts lists of human gene identifiers (IDs) including HUGO gene symbols, accession numbers of INSD (DDBJ/EMBL/GenBank), UniProt accession numbers, Gene IDs, Ensembl Gene IDs, H-InvDB Transcript IDs (HIT) and Locus IDs (HIX), etc. Then, HEAT converts the accepted IDs into HIX using the ID Converter System ("http://biodb.jp/":http://biodb.jp/), collects various annotations of H-InvDB representative transcripts, and conducts statistical tests by using Fisher's exact probability. The output of HEAT is a simple report of annotations commonly found among the query genes, which is very useful to grasp the property of a particular gene set. HEAT is freely available at "http://hinv.jp/HEAT/":http://hinv.jp/HEAT/

CIPRO 2.5: Ciona intestinalis protein database, a unique integrated repository of large-scale omics data, bioinformatic analyses and curated annotation, with user rating and reviewing functionality

The Ciona intestinalis protein database (CIPRO) is an integrated protein database for the tunicate species C. intestinalis. The database is unique in two respects: first, because of its phylogenetic position, Ciona is suitable model for understanding vertebrate evolution; and second, the database includes original large-scale transcriptomic and proteomic data. Ciona intestinalis has also been a favorite of developmental biologists. Therefore, large amounts of data exist on its development and morphology, along with a recent genome sequence and gene expression data. The CIPRO database is aimed at collecting those published data as well as providing unique information from unpublished experimental data, such as 3D expression profiling, 2D-PAGE and mass spectrometry-based large-scale analyses at various developmental stages, curated annotation data and various bioinformatic data, to facilitate research in diverse areas, including developmental, comparative and evolutionary biology. For medical and evolutionary research, homologs in humans and major model organisms are intentionally included. The current database is based on a recently developed KH model containing 36 034 unique sequences, but for higher usability it covers 89 683 all known and predicted proteins from all gene models for this species. Of these sequences, more than 10 000 proteins have been manually annotated. Furthermore, to establish a community-supported protein database, these annotations are open to evaluation by users through the CIPRO website. CIPRO 2.5 is freely accessible at http://cipro.ibio.jp/2.5

CIPRO 2.5: Ciona intestinalis Protein integrated database with large-scale omics data, bioinformatic analyses and curated annotation, with ability for user rating and comments

CIPRO database is an integrated protein database for a tunicate species Ciona intestinalis that belongs to the Urochordata. Although the CIPRO database deals with proteomic and transcriptomic data of a single species, the animal is considered unique in the evolutionary tree, representing a possible origin of the vertebrates and is a good model for understanding chordate evolution, including that of humans. Furthermore, C. intestinalis has been one of the favorites of developmental biologists; there exists a huge amount of accumulated knowledge on its development and morphology, in addition to the recent genome sequence and gene expression data. The CIPRO database is aimed at not only collecting published data, but also presenting unique information, including the unpublished transcriptomic and proteomic data and human curated annotation, for the use by researchers in broad research fields of biology and bioinformatics

Genetic association between the interleukin-2 receptor-alpha gene and mode of onset of type 1 diabetes in the Japanese population.

CONTEXT/OBJECTIVE: The IL-2 receptor-alpha (IL2RA), also known as CD25, is expressed on the regulatory T cells, which play an important role in the control of immune responses and the maintenance of immune homeostasis. Our objective was to determine whether variants in the IL2RA gene are associated with type 1 diabetes in the Japanese population. DESIGN/PATIENTS: We genotyped the four single-nucleotide polymorphisms (rs706778, rs3118470, ss52580101, and rs11594656) of the IL2RA in 885 patients with type 1 diabetes and 606 control subjects of Japanese origin. The allele and genotype frequencies were examined in the patient groups stratified by their mode of onset in a case-control study. RESULTS: We found evidence of association with acute-onset, but not slow-onset and fulminant, type 1 diabetes for two of the four single-nucleotide polymorphisms genotyped (rs706778 and rs3118470). The rs706778 A allele and the rs3118470 G allele were associated with an increased disease risk [odds ratio (OR) for rs706778 AA genotype 1.54, P = 4.2 x 10(-4) and OR for rs3118470 GG genotype 1.50, P = 0.0019, respectively]. Furthermore, the A-G haplotype was associated with increased type 1 diabetes risk in the acute-onset form (OR 1.30, P = 0.002). CONCLUSIONS: The present data confirm the type 1 diabetes association with IL2RA and provide evidence that the different contributions of the IL2RA in the susceptibility to acute-onset and other forms of type 1 diabetes in the Japanese population

Altered structural hippocampal intra-networks in a general elderly Japanese population with mild cognitive impairment

Abstract Although altered networks inside the hippocampus (hippocampal intra-networks) have been observed in dementia, the evaluation of hippocampal intra-networks using magnetic resonance imaging (MRI) is challenging. We employed conventional structural imaging and incident component analysis (ICA) to investigate the structural covariance of the hippocampal intra-networks. We aimed to assess altered hippocampal intra-networks in patients with mild cognitive impairment (MCI). A cross-sectional study of 2122 participants with 3T MRI (median age 69 years, 60.9% female) were divided into 218 patients with MCI and 1904 cognitively normal older adults (CNOA). By employing 3D T1-weighted imaging, voxels within the hippocampus were entered into the ICA analysis to extract the structural covariance intra-networks within the hippocampus. The ICA extracted 16 intra-networks from the hippocampal structural images, which were divided into two bilateral networks and 14 ipsilateral networks. Of the 16 intra-networks, two (one bilateral network and one ipsilateral networks) were significant predictors of MCI from the CNOA after adjusting for age, sex, education, disease history, and hippocampal volume/total intracranial volume ratio. In conclusion, we found that the relationship between hippocampal intra-networks and MCI was independent from the hippocampal volume. Our results suggest that altered hippocampal intra-networks may reflect a different pathology in MCI from that of brain atrophy