Biology subjects

Katsuoka, F.

Publications and source records attributed to Katsuoka, F..

8 recordsLinked to original sources

bioRxiv2025

ibSLS: A Biobank for Democratizing Access to Multi-Omics Data and Biospecimens from Spaceflight Research

During spaceflight, astronauts are exposed to extreme conditions such as microgravity, cosmic radiation, and confinement, which can cause a wide range of health problems. To elucidate the molecular mechanisms underlying these issues and to develop intervention strategies for maintaining physiological homeostasis during space missions, space life science research using mouse models is actively conducted on the International Space Station (ISS). However, because of the high cost and technical complexity of spaceflight experiments, it is critical to maximize the scientific value of each mission by ensuring broad accessibility to both data and biospecimens. To this end, we developed the integrated biobank for Space Life Sciences (ibSLS; https://ibsls.megabank.tohoku.ac.jp), a data-visualization and sample-sharing platform that provides access to transcriptomic and metabolomic datasets generated from JAXAs Mouse Habitat Unit (MHU) missions. The platform features a user-friendly interface, tools for cross-mission analysis, and integration with human multi-omics databases, enabling cross-species comparisons. In addition, ibSLS facilitates biospecimen requests to support downstream research. By promoting open access to spaceflight-derived data and biological resources, ibSLS encourages the participation of researchers from diverse fields in space life science. We believe that ibSLS will make a valuable contribution to both biomedical research on spaceflight-related health issues and the study of diseases on Earth.

bioinformatics↗

bioRxiv2024

JG2: an updated version of the Japanese population-specific reference genome

This study presents the construction of JG2, an updated population-specific reference genome for the Japanese population. Utilizing data from three individuals previously employed in the construction of JG1, several methodologies were employed to enhance genomic coverage and assembly quality. Hi-C sequencing technology facilitated phase-aware assembly, generating two haploid assemblies per individual and enabling improved representation of genetic variation. A meta-assembly strategy and a majority decision approach further refined assembly quality by combining the best sequences from multiple assemblies and minimizing the inclusion of rare variants. The resulting JG2 genome comprises chromosome-level sequences, mitochondrial chromosomes, and unplaced scaffolds, offering more comprehensive coverage of the Japanese genome. Comparative analyses with other reference genomes demonstrated the accuracy and representativeness of JG2, highlighting its utility for genetic research involving the Japanese population. Overall, by adopting the phased assembly technique, JG2 represents a significant advancement over the collapsed assembly-based JG1, providing researchers with a more precise and comprehensive resource for understanding the genetic landscape of the Japanese population. The sequences and annotations are available on the jMorp website (https://jmorp.megabank.tohoku.ac.jp/).

genomics↗

bioRxiv2022

PNPO-PLP Axis Senses Prolonged Hypoxia by Regulating Lysosomal Activity

Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen sensing systems inducing acute hypoxic response, including HIF pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here, we show that pyridoxine 5-phosphate oxidase (PNPO) that catalyzes bioactivation of vitamin B6 serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decline of PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5-phosphate (PLP), and inhibited lysosomal activity, leading to the augmentation of inflammatory response of macrophages. The PNPO-PLP axis creates a distinct layer of oxygen sensing, which gradually turns down and up the PLP-dependent metabolism according to prolonged changes in oxygen availability.

biochemistry↗

bioRxiv2020

Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes in a 3,552 Japanese whole-genome sequence dataset (3.5KJPNv2)

Identification of pathogenic germline variants yet no clinical evidence in BRCA genes has become important in patient care of hereditary breast and ovarian cancer syndrome (HBOC). Computational scoring and prospective cohort studies may help to identify such pathogenic variants. We annotated the variants in the BRCA1 and BRCA2 genes from a dataset of 3,552 whole-genome sequences obtained from members of the genome cohorts by Tohoku Medical Megabank Project (TMM) with the InterVar software. Computational impact scores (CADD_phred and Eigen_raw) and minor allele frequencies (MAF) of pathogenic (P) and likely pathogenic (LP) variants in ClinVar are used for filtration criteria. Familial predispositions in cancers among the 35,000 TMM genome cohort participants are analyzed to verify the pathogenicity. Seven potentially pathogenic variants were newly identified. Carriers of these potential pathogenic variants and definite P and LP variants among participants of the TMM prospective cohort show a statistically significant preponderance in cancer onset in sisters in the self-reported cancer history. Filtering by computational scoring and MAF is useful to identify potential pathogenic variants in BRCA genes for Japanese population. These results will be helpful to follow up the carriers of variants of uncertain significance in the HBOC genes.

genetics↗

bioRxiv2020

Enhancer Remodeling Promotes Tumor-Initiating Activity in NRF2-Activated Non-Small Cell Lung Cancers

Transcriptional dysregulation, which can be caused by genetic and epigenetic alterations, is a fundamental feature of many cancers. A key cytoprotective transcriptional activator, NRF2, is often aberrantly activated in non-small cell lung cancers (NSCLCs) and supports both aggressive tumorigenesis and therapeutic resistance. Herein, we found that persistently activated NRF2 in NSCLCs generates enhancers at gene loci that are not normally regulated by transiently activated NRF2 under physiological conditions. Elevated accumulation of CEBPB in NRF2-activated NSCLCs was found to be one of the prerequisites for establishment of the unique NRF2-dependent enhancers, among which NOTCH3 enhancer was shown to be critical for the promotion of tumor-initiating activity. Enhancer remodeling mediated by NRF2-CEBPB cooperativity promotes tumor-initiating activity and drives malignancy of NRF2-activated NSCLCs via establishment of the NRF2-NOTCH3 regulatory axis.

cancer biology↗

bioRxiv2019

Construction and Integration of Three De Novo Japanese Human Genome Assemblies toward a Population-Specific Reference

The complete sequence of the human genome is used as a reference for next-generation sequencing analyses. However, some ethnic ancestries are under-represented in the international human reference genome (e.g., GRCh37), especially Asian populations, due to a strong bias toward European and African ancestries in a single mosaic haploid genome consisting chiefly of a single donor. Here, we performed de novo assembly of the genomes from three Japanese male individuals using >100x PacBio long reads and Bionano optical maps per sample. We integrated the genomes using the major allele for consensus, and anchored the scaffolds using sequence-tagged site markers from conventional genetic and radiation hybrid maps to reconstruct each chromosome sequence. The resulting genome sequence, designated JG1, is highly contiguous, accurate, and carries the major allele in the majority of single nucleotide variant sites for a Japanese population. We adopted JG1 as the reference for confirmatory exome re-analyses of seven Japanese families with rare diseases and found that re-analysis using JG1 reduced false-positive variant calls versus GRCh37 while retaining disease-causing variants. These results suggest that integrating multiple genome assemblies from a single ethnic population can aid next-generation sequencing analyses of individuals originated from the population.

genomics↗

bioRxiv2019

A Recurrent Neural Network Based Method for Genotype Imputation on Phased Genotype Data

Genotype imputation estimates genotypes of unobserved variants from genotype data of other observed variants, and such estimation is enabled using haplotype data of a large number of other individuals. Although existing imputation methods explicitly use haplotype data, the accessibility of haplotype data is often limited because the agreement is necessary from donors of genome data. We propose a new imputation method that uses bidirectional recurrent neural network, and haplotype data of a large number of individuals are encoded as its model parameters through the training step, which can be shared publicly due to the difficulty in restoring genotype data at the individual-level. In the performance evaluation using the phased genotype data in the 1000 Genomes Project, the imputation accuracy of the proposed method in R2 is comparative with existing methods for variants with MAF [≥] 0.05 and is slightly worse than those of the existing methods for variants with MAF < 0.05. In a scenario of limited availability of haplotype data to the existing methods, the accuracy of the proposed method is higher than those of the existing methods at least for variants with MAF [≥] 0.005. Python code of our implementation for imputation is available at https://github.com/kanamekojima/rnnimp/.

bioinformatics↗

bioRxiv2019

3.5KJPNv2, An allele frequency panel of 3,552 Japanese Individuals

The first step towards realizing personalized healthcare is to catalog the genetic variations in a population. Since the dissemination of individual-level genomic information is strictly controlled, it will be useful to construct population-level allele frequency panels and to provide them through easy-to-use interfaces. In the Tohoku Medical Megabank Project, we have sequenced nearly 4,000 individuals from a Japanese population, and constructed an allele frequency panel of 3,552 individuals after removing related samples. The panel is called the 3.5KJPNv2. It was constructed by using a standard pipeline including the 1KGP and gnomAD algorithms to reduce technical biases and to allow comparisons to other populations. Our database is the first largescale panel providing the frequencies of variants present on the X chromosome and on the mitochondria in the Japanese population. All the data are available on our original database at https://jmorp.megabank.tohoku.ac.jp.

genomics↗