Article

H-DBAS: human-transcriptome database for alternative splicing: update 2010

Integrated Database and Systems Biology Team, Biomedicinal Information Research Center National Institute of Advanced Industrial Science and Technology, AIST Bio-IT Research Bldg Aomi 2-4-7, Koto-ku, Tokyo 135-0064, Japan.
Nucleic Acids Research (Impact Factor: 8.81). 12/2009; 38(Database issue):D86-90. DOI: 10.1093/nar/gkp984
Source: PubMed

ABSTRACT H-DBAS (http://h-invitational.jp/h-dbas/) is a specialized database for human alternative splicing (AS) based on H-Invitational full-length cDNAs. In this update, for better annotations of AS events, we correlated RNA-Seq tag information to the AS exons and splice junctions. We generated a total of 148,376,598 RNA-Seq tags from RNAs extracted from cytoplasmic, nuclear and polysome fractions. Analysis of the RNA-Seq tags allowed us to identify 90,900 exons that are very likely to be used for protein synthesis. On the other hand, 254 AS junctions of human RefSeq transcripts are unique to nuclear RNA and may not have any translational consequences. We also present a new comparative genomics viewer so that users can empirically understand the evolutionary turnover of AS. With the unique experimental data closely connected with intensively curated cDNA information, H-DBAS provides a unique platform for the analysis of complex AS.

0 Followers
 · 
135 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alternative splicing is a pervasive mechanism of RNA maturation in higher eukaryotes, which increases proteomic diversity and biological complexity. It has a key regulatory role in several physiological and pathological states. The diffusion of Next Generation Sequencing, particularly of RNA-Sequencing, has exponentially empowered the identification of novel transcripts revealing that more than 95% of human genes undergo alternative splicing. The highest rate of alternative splicing occurs in transcription factors encoding genes, mostly in Krüppel-associated box domains of zinc finger proteins. Since these molecules are responsible for gene expression, alternative splicing is a crucial mechanism to "regulate the regulators". Indeed, different transcription factors isoforms may have different or even opposite functions. In this work, through a targeted re-analysis of our previously published RNA-Sequencing datasets, we identified nine novel transcripts in seven transcription factors genes. In silico analysis, combined with RT-PCR, cloning and Sanger sequencing, allowed us to experimentally validate these new variants. Through computational approaches we also predicted their novel structural and functional properties. Our findings indicate that alternative splicing is a major determinant of transcription factor diversity, confirming that accurate analysis of RNA-Sequencing data can reliably lead to the identification of novel transcripts, with potentially new functions.
    International Journal of Molecular Sciences 01/2014; 16(1):1755-71. DOI:10.3390/ijms16011755 · 2.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gene expression is regulated by trans-acting transcription factors and microRNAs (miRNAs) through interactions with their respective cis-regulatory elements. The effects that drugs induce result from complex interactions in pathways downstream from their primary targets. These interactions, from gene regulatory apparatus and from drug-induced pathways, form a complex, multilayered network. Knowing that drugs can perturb miRNA expression profiles, a genomewide analysis of drug-induced intronic miRNA perturbations has been presented here. By comparative analysis of control and drugged data sets from 27 independent gene expression experiments, it was feasible to detect the effect of drugs on miRNA target genes. Signatures of 21 of 28 miRNAs, predicted to be influenced by drug action, were detected. This study demonstrates that the action of drugs on mRNA expression can be mediated through the combinatorial effects of miRNAs. In addition, transcription factors, through miRNAs within the introns of their target genes, can exert an indirect effect on the expression of distal mRNAs.
    Pharmacogenetics and Genomics 01/2015; DOI:10.1097/FPC.0000000000000111 · 3.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The completion of the Human Genome Project lays a foundation for systematically studying the human genome from evolutionary history to precision medicine against diseases. With the explosive growth of biological data, there is an increasing number of biological databases that have been developed in aid of human-related research. Here we present a collection of human-related biological databases and provide a mini-review by classifying them into different categories according to their data types. As human-related databases continue to grow not only in count but also in volume, challenges are ahead in big data storage, processing, exchange and curation. Copyright © 2015. Production and hosting by Elsevier Ltd.
    Genomics Proteomics & Bioinformatics 02/2015; 42(1). DOI:10.1016/j.gpb.2015.01.006