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Kinoshita K.,Tohoku UniversityMiyagi
Transactions of Japanese Society for Medical and Biological Engineering | Year: 2014

According to the progress of genome sequencing technology, the cost of genome analyses is rapidly decreasing, and the feasibility of genome-based personalized healthcare is dramatically increasing. Actually, a lot of large-scale genome cohort studies are established to realize personalized healthcare. Tohoku University is also constructing a new genome cohort in the process of constructive recoveries from the Great East Japan Earthquake on March 11, 2011. On the other hands, the cost of information analyses of genome data is not decreased, mainly due to the increase of the amount of data produced by new generation sequencers and high sensitivity of the data. In this talk, I will introduce our approaches to build a basis of in-silico analyses though the setup of a new computer system in Tohoku Medical Megabank, and discuss some issues in information analyses to realize the genome-based personalized healthcare. © 2014, Japan Soc. of Med. Electronics and Biol. Engineering. All rights reserved.

Oji Y.,Osaka University | Hashimoto N.,Osaka University | Tsuboi A.,Osaka University | Murakami Y.,Osaka University | And 22 more authors.
International Journal of Cancer | Year: 2016

We previously evaluated Wilms’ tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA-A*24:02 restricted, 9-mer WT1-235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1-235-specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1-235 peptide (WT1-235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine. The WT1-235 IgG antibody, which was undetectable before vaccination, became detectable in 30 (50.8%) of a total of 59 patients during 3 months of WT1 peptide vaccination. The dominant WT1-235 IgG antibody subclass was Th1-type, IgG1 and IgG3. WT1-235 IgG antibody production was significantly and positively correlated with both progression-free survival (PFS) and overall survival (OS). Importantly, the combination of WT1-235 IgG antibody production and positive delayed type-hypersensitivity (DTH) to the WT1-235 peptide was a better prognostic marker for long-term OS than either parameter alone. These results suggested that WT1-235 peptide vaccination induces not only WT1-235-specific CTLs as previously described but also WT1-235-specific humoral immune responses associated with antitumor cellular immune response. Our results indicate that the WT1 IgG antibody against the WT1 peptide may be a useful predictive marker, with better predictive performance in combination with DTH to WT1 peptide, and provide a new insight into the antitumor immune response induction in WT1 peptide vaccine-treated patients. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC

Nishi H.,Applied Information Sciences | Nakata J.,Tohoku UniversityMiyagi | Kinoshita K.,Applied Information Sciences | Kinoshita K.,Tohoku UniversityMiyagi
Protein Science | Year: 2016

Recent advances in DNA sequencing techniques have identified rare single-nucleotide variants with less than 1% minor allele frequency. Despite the growing interest and physiological importance of rare variants in genome sciences, less attention has been paid to the allele frequency of variants in protein sciences. To elucidate the characteristics of genetic variants on protein interaction sites, from the viewpoints of the allele frequency and the structural position of variants, we mapped about 20,000 human SNVs onto protein complexes. We found that variants are less abundant in protein interfaces, and specifically the core regions of interfaces. The tendency to “avoid” the interfacial core is stronger among common variants than rare variants. As amino acid substitutions, the trend of mutating amino acids among rare variants is consistent in different interfacial regions, reflecting the fact that rare variants result from random mutations in DNA sequences, whereas amino acid changes of common variants vary between the interfacial core and rim regions, possibly due to functional constraints on proteins. This study illustrated how the allele frequency of variants relates to the protein structural regions and the functional sites in general and will lead to deeper understanding of the potential deleteriousness of rare variants at the structural level. Exceptional cases of the observed trends will shed light on the limitations of structural approaches to evaluate the functional impacts of variants. Published by Wiley-Blackwell. © 2015 The Protein Societ

Otaka K.,Tohoku UniversityMiyagi | Hiradate Y.,Tohoku UniversityMiyagi | Kobayashi N.,Tohoku UniversityMiyagi | Shirakata Y.,Tohoku UniversityMiyagi | Tanemura K.,Tohoku UniversityMiyagi
Journal of Reproduction and Development | Year: 2015

During mammalian spermatogenesis, spermatogenic cells undergo mitotic division and are subsequently divided into haploid spermatids by meiotic division, but the dynamics of sex chromosomes during spermatogenesis are unclear in vivo. To gain insight into the distribution of sex chromosomes in the testis, we examined the localization of sex chromosomes before and after meiosis in mouse testis sections. Here, we developed a method of fluorescence in situ hybridization (FISH) using specific probes for the X and Y chromosomes to obtain their positional information in histological testis sections. FISH analysis revealed the sex chromosomal position during spermatogenesis in each stage of seminiferous epithelia and in each spermatogenic cell. In the spermatogonia and leptotene spermatocytes, sex chromosomes were distantly positioned in the cell. In the zygotene and pachytene spermatocytes at prophase I, X and Y chromosomes had a random distribution. After meiosis, the X and Y spermatids were random in every seminiferous epithelium. We also detected aneuploidy of sex chromosomes in spermatogenic cells using our developed FISH analysis. Our results provide further insight into the distribution of sex chromosomes during spermatogenesis, which could help to elucidate a specific difference between X and Y spermatids and sex chromosome-specific behavior. © 2015 by the Society for Reproduction and Development.

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