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Journal Articles

The H-Invitational Database (H-InvDB); A Comprehensive annotation resource for human genes and transcripts

Yamasaki, Chisato*; Murakami, Katsuhiko*; Fujii, Yasuyuki*; Sato, Yoshiharu*; Harada, Erimi*; Takeda, Junichi*; Taniya, Takayuki*; Sakate, Ryuichi*; Kikugawa, Shingo*; Shimada, Makoto*; et al.

Nucleic Acids Research, 36(Database), p.D793 - D799, 2008/01

 Times Cited Count:51 Percentile:71.37(Biochemistry & Molecular Biology)

Here we report the new features and improvements in our latest release of the H-Invitational Database, a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of fulllength cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 protein-coding and 642 non-protein-coding loci; 858 transcribed loci overlapped with predicted pseudogenes.

Journal Articles

Contribution of computational biology and structural genomics to understand genome and transcriptome

Go, Michiko*; Yura, Kei; Shionyu, Masafumi*

Frontiers of Computational Science, p.75 - 80, 2007/00

Genome sequencing and structural genomics projects are both proceeded to gain a new perspective of life, that is global views on mechanisms of life with comprehensive and unbiased fashion. We now have genome sequences of human and other species, and are going to have a three-dimensional structure of whole proteins. Those massive pieces of information can only be deciphered with collaboration of computational biology. In this paper, we will discuss the amount of data we have at the moment and one of the new views on mechanisms of cellular function regulation obtained based on the computational analyses of those data.

Journal Articles

Alternative splicing in human transcriptome; Functional and structural influence on proteins

Yura, Kei; Shionyu, Masafumi*; Hagino, Kei*; Hijikata, Atsushi*; Hirashima, Yoshinori*; Nakahara, Taku*; Eguchi, Tatsuya*; Shinoda, Kazuki*; Yamaguchi, Akihiro*; Takahashi, Kenichi*; et al.

Gene, 380(2), p.63 - 71, 2006/10

 Times Cited Count:55 Percentile:72.39(Genetics & Heredity)

Alternative splicing is a molecular mechanism that produces multiple proteins from a single gene, and is thought to produce variety in proteins translated from a limited number of genes. Here we analyzed how alternative splicing produced variety in protein structure and function, by using human full-length cDNAs, on the assumption that all of the alternatively spliced mRNAs were translated to proteins. We found that the length of alternatively spliced amino acid sequences, in most cases, fell into a size shorter than that of average protein domain. We evaluated comprehensively the presumptive three-dimensional structures of the alternatively spliced products to assess the impact of alternative splicing on gene function. We found that more than half of the products encoded proteins which were involved in signal transduction, transcription and translation, and more than half of alternatively spliced regions comprised interaction sites between proteins and their binding partners, including substrates, DNA/RNA, and other proteins. Intriguingly, 67% of the alternatively spliced isoforms showed significant alterations to regions of the protein structural core, which likely resulted in large conformational change. Based on those findings, we speculate that there are a large number of cases that alternative splicing modulates protein networks through significant alteration in protein conformation.

Journal Articles

Large-scale identification and characterization of alternative splicing variants of human gene transcripts using 56 419 completely sequenced and manually annotated full-length cDNAs

Takeda, Junichi*; Suzuki, Yutaka*; Nakao, Mitsuteru*; Barrero, R. A.*; Koyanagi, Kanako*; Jin, L.*; Motono, Chie*; Hata, Hiroko*; Isogai, Takao*; Nagai, Keiichi*; et al.

Nucleic Acids Research, 34(14), p.3917 - 3928, 2006/00

 Times Cited Count:34 Percentile:54.48(Biochemistry & Molecular Biology)

We report the first genome-wide identification and characterization of alternative splicing in human gene transcripts based on analysis of the full-length cDNAs. Applying both manual and computational analyses for 56 419 completely sequenced and precisely annotated full-length cDNAs selected for the H-Invitational human transcriptome annotation meetings, we identified 6877 alternative splicing genes with 18 297 different alternative splicing variants. A total of 37 670 exons were involved in these alternative splicing events. The encoded protein sequences were affected in 6005 of the 6877 genes. Notably, alternative splicing affected protein motifs in 3015 genes, subcellular localizations in 2982 genes and transmembrane domains in 1348 genes. Genome-wide annotations of alternative splicing, relying on full-length cDNAs, should lay firm groundwork for exploring in detail the diversification of protein function which is mediated by the alternative splicing variants.

Oral presentation

Systematic detection of protein regions affected by alternative splicing

Shionyu, Masafumi*; Yura, Kei; Hijikata, Atsushi*; Nakahara, Taku*; Shinoda, Kazuki*; Yamaguchi, Akihiro*; Takahashi, Kenichi*; Go, Michiko*

no journal, , 

Alternative splicing (AS) is a cellular process where multiple mature mRNAs are produced from a single gene by different usage of exons. From computational and experimental approaches, it is estimated that 30-70% of human genes undergo alternative splicing. There are a number of reports on spliced mRNAs involved in biological processes, yet functional analyses of a large number of proteins produced by AS remain to be performed. Functional analyses of these proteins by experiments are time-consuming, and therefore, a computational approach that can estimate effect of AS on proteins is required. We have developed a pipeline that can systematically detect AS regions, which are defined as protein regions modified by alternatively spliced exon, using genomic sequences and full-length transcripts data. The pipeline further assigned AS regions to protein three-dimensional structures and can estimate effects of AS on protein conformation stability and functional sites. We analyzed human AS regions using our pipeline and found that about half of AS regions fell into a size shorter than 100 amino acid residues. We, then, assessed the relationship between AS regions and protein structural domains and found that about 40% of AS regions were placed within a domain and the ratio of AS regions corresponding to domains was only about 10%. This result suggests that AS regulates protein function through alteration of segments within a domain rather than through switching protein domains. We will discuss how AS regulates protein function through alteration of segments within a domain.

Oral presentation

Relationship between genome and protein structures in eukaryotes

Yura, Kei; Shionyu, Masafumi*; Go, Michiko*

no journal, , 

Open reading frames in eukaryotic genome is composed of introns and exons, and selection of appropirate exons is the mechanism of alternative splicing. In this lecture, we will discuss the correlation of intron/exon structures with protein three-dimensional structures and effect of alternative splicing in protein structures.

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