Identification of epistatic SNP combinations in rheumatoid arthritis using LAMPLINK and Japanese cohorts.

Genome-wide association studies have enabled the identification of important genetic factors in many trait studies. However, only a fraction of the heritability can be explained by known genetic factors, even in the most common diseases. Genetic loci combinations, or epistatic contributions expressed by combinations of single nucleotide polymorphisms (SNPs), have been argued to be one of the critical factors explaining some of the missing heritability, especially in oligogenic/polygenic diseases.

Comprehensive HLA Typing from a Current Allele Database Using Next-Generation Sequencing Data.

HLA allele information is essential for a variety of medical applications, such as genomic studies of multifactorial diseases, including immune system and inflammation-related disorders, and donor selection in organ transplantation and regenerative medicine. To obtain this information, an accurate HLA typing method that is applicable for any allele registered in HLA allele databases is needed. Here we describe a method-called HLA-HD-for determining alleles from a current HLA database using next-generation sequencing (NGS) results.

A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study.

Gut-microbiota derived metabolites are important regulators of host biology and metabolism. To understand the impacts of the microbial metabolite 4-cresol sulfate (4-CS) on four chronic diseases [type 2 diabetes mellitus, metabolic syndrome (MetS), non-alcoholic fatty liver disease, and chronic kidney disease (CKD)], we conducted association analyses of plasma 4-CS quantified by liquid chromatography coupled to mass spectrometry (LC-MS) in 3641 participants of the Nagahama study. Our results validated the elevation of 4-CS in CKD and identified a reducing trend in MetS.

Improved genetic prediction of the risk of knee osteoarthritis using the risk factor-based polygenic score.

Background: Polygenic risk score (PRS) analysis is used to predict disease risk. Although PRS has been shown to have great potential in improving clinical care, PRS accuracy assessment has been mainly focused on European ancestry. This study aimed to develop an accurate genetic risk score for knee osteoarthritis (OA) using a multi-population PRS and leveraging a multi-trait PRS in the Japanese population.

Identification of risk factors for elevated serum IgG4 levels in subjects in a large-scale health checkup cohort study.

Introduction: To allow the identification of IgG4-related disease (IgG4-RD) from a subclinical phase as it is important to understand the risk of elevated serum IgG4 levels. We planned to evaluate serum IgG4 levels in the participants of the Nagasaki Islands Study (NaIS), a large-scale health checkup cohort study.

Methods: This study included 3,240 individuals who participated in the NaIS between 2016 and 2018 and consented to participate in the study.

Genetic influences on human blood metabolites in the Japanese population.

An increase in ethnic diversity in genetic studies has the potential to provide unprecedented insights into how genetic variations influence human phenotypes. In this study, we conducted a quantitative trait locus (QTL) analysis of 121 metabolites measured using gas chromatography-mass spectrometry with plasma samples from 4,888 Japanese individuals. We found 60 metabolite-gene associations, of which 13 have not been previously reported.

Physical and financial impacts caused by the COVID-19 pandemic exacerbate knee pain: A longitudinal study of a large-scale general population.

Objectives: This study aimed to evaluate the changes in knee pain, a dominant cause of physical disability, following the coronavirus disease (COVID-19) pandemic, and to identify factors affecting the changes in knee pain.

Methods: We analysed the pre- and post-COVID-19 longitudinal data set of the Nagahama Study. Knee pain was assessed using the Knee Society Score (KSS).

Genome wide association study of HTLV-1-associated myelopathy/tropical spastic paraparesis in the Japanese population.

HTLV-1-associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers.

High-Definition Genomic Analysis of HLA Genes Via Comprehensive HLA Allele Genotyping.

HLA is essential for various medical applications, such as genomic studies of multifactorial diseases, including immune system and inflammation-related disorders. Therefore, an accurate HLA typing method that is applicable for any allele registered in HLA allele databases is required to deduce scientific evidence related to disorders. Here, we describe a method for determining HLA alleles from next-generation sequencing (NGS) results by using currently available HLA sequence data in public HLA databases and show its application in association analysis.

Combination of host immune metabolic biomarkers for the PD-1 blockade cancer immunotherapy.

BACKGROUNDCurrent clinical biomarkers for the programmed cell death 1 (PD-1) blockade therapy are insufficient because they rely only on the tumor properties, such as programmed cell death ligand 1 expression frequency and tumor mutation burden. Identifying reliable, responsive biomarkers based on the host immunity is necessary to improve the predictive values.METHODSWe investigated levels of plasma metabolites and T cell properties, including energy metabolism markers, in the blood of patients with non-small cell lung cancer before and after treatment with nivolumab (n = 55).

IgG4-related disease in the Japanese population: a genome-wide association study.

Background: IgG4-related disease is a newly recognised immunopathological entity that includes autoimmune pancreatitis, IgG4-related sialadenitis, and IgG4-related kidney disease. To understand the genetic landscape of IgG4-related disease, we did a genome-wide association study.

Methods: We did a genome-wide association study of Japanese individuals, initially screening 857 patients with IgG4-related disease at 50 Japanese research institutions and DNA samples from 2082 healthy control participants from the Nagahama Prospective Genome Cohort for the Comprehensive Human Bioscience.

Comprehensive HLA Typing from a Current Allele Database Using Next-Generation Sequencing Data.

HLA allele information is essential for a variety of medical applications, such as genomic studies of multifactorial diseases, including immune system and inflammation-related disorders, and donor selection in organ transplantation and regenerative medicine. To obtain this information, an accurate HLA typing method that is applicable for any allele registered in HLA allele databases is needed. Here, we describe a method for determining alleles from a current HLA database using next-generation sequencing (NGS) results.

HLA-HD: An accurate HLA typing algorithm for next-generation sequencing data.

The accurate typing of human leukocyte antigen (HLA) alleles is critical for a variety of medical applications, such as genomic studies of multifactorial diseases, including immune system and inflammation-related disorders, and donor selection in organ transplantation and regenerative medicine. Here, we developed a new algorithm for determining HLA alleles using next-generation sequencing (NGS) results. The method consists of constructing an extensive dictionary of HLA alleles, precise mapping of the NGS reads, and calculating a score based on weighted read counts to select the most suitable pair of alleles.

A promoter-level mammalian expression atlas.

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles.

Positional correlation analysis improves reconstruction of full-length transcripts and alternative isoforms from noisy array signals or short reads.

Motivation: A reconstruction of full-length transcripts observed by next-generation sequencer or tiling arrays is an essential technique to know all phenomena of transcriptomes. Several techniques of the reconstruction have been developed. However, problems of high-level noises and biases still remain and interrupt the reconstruction.

ARTADE2DB: improved statistical inferences for Arabidopsis gene functions and structure predictions by dynamic structure-based dynamic expression (DSDE) analyses.

Recent advances in technologies for observing high-resolution genomic activities, such as whole-genome tiling arrays and high-throughput sequencers, provide detailed information for understanding genome functions. However, the functions of 50% of known Arabidopsis thaliana genes remain unknown or are annotated only on the basis of static analyses such as protein motifs or similarities. In this paper, we describe dynamic structure-based dynamic expression (DSDE) analysis, which sequentially predicts both structural and functional features of transcripts.

Arabidopsis tiling array analysis to identify the stress-responsive genes.

Plants respond and adapt to drought, cold, and high-salinity stresses. Stress-inducible gene products function in the stress response and tolerance in plants. Using cDNA microarrays and oligonucleotide microarrays, stress-inducible genes have been identified in various plant species so far.

PosMed-plus: an intelligent search engine that inferentially integrates cross-species information resources for molecular breeding of plants.

Molecular breeding of crops is an efficient way to upgrade plant functions useful to mankind. A key step is forward genetics or positional cloning to identify the genes that confer useful functions. In order to accelerate the whole research process, we have developed an integrated database system powered by an intelligent data-retrieval engine termed PosMed-plus (Positional Medline for plant upgrading science), allowing us to prioritize highly promising candidate genes in a given chromosomal interval(s) of Arabidopsis thaliana and rice, Oryza sativa.

OmicBrowse: a Flash-based high-performance graphics interface for genomic resources.

OmicBrowse is a genome browser designed as a scalable system for maintaining numerous genome annotation datasets. It is an open source tool capable of regulating multiple user data access to each dataset to allow multiple users to have their own integrative view of both their unpublished and published datasets, so that the maintenance costs related to supplying each collaborator exclusively with their own private data are significantly reduced. OmicBrowse supports DAS1 imports and exports of annotations to Internet site servers worldwide.