The opposite aging effect to single cell transcriptome profile among cell subsets.

Comparing transcriptome profiling between younger and older samples reveals genes related to aging and provides insight into the biological functions affected by aging. Recent research has identified sex, tissue, and cell type-specific age-related changes in gene expression. This study reports the overall picture of the opposite aging effect, in which aging increases gene expression in one cell subset and decreases it in another cell subset.

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.

Data-driven detection of age-related arbitrary monotonic changes in single-cell gene expression distributions.

Identification of genes whose expression increases or decreases with age is central to understanding the mechanisms behind aging. Recent scRNA-seq studies have shown that changes in single-cell expression profiles with aging are complex and diverse. In this study, we introduce a novel workflow to detect changes in the distribution of arbitrary monotonic age-related changes in single-cell expression profiles.

The medical cost and outcome of desensitization protocol in kidney transplantation recipients with high immunological risks.

Background: Kidney transplantation is a well-established alternative in renal replacement therapy. Compared with hemodialysis, low-immunological-risk kidney transplantation can reduce the medical treatment costs associated with end-stage renal disease. However, there are few reports on whether high-immunological-risk kidney transplantation reduces the financial burden on governments.

Visualization of the landscape of the read alignment shape of ATAC-seq data using Hellinger distance metric.

Assay for Transposase-Accessible Chromatin using high-throughput sequencing (ATAC-seq) is the popular technique using next-generation sequencing to measure chromatin accessibility and identify open chromatin regions. While read alignment shape information of next-generation sequencing data with intensity information has been used in various bioinformatics methods, few studies have focused on pure shape information alone. In this study, we investigated what types of ATAC-seq read alignment shapes are observed for the promoter region and whether the pure shape information was related or unrelated to other gene features.

Delving into gene-set multiplex networks facilitated by a k-nearest neighbor-based measure of similarity.

Gene sets are functional units for living cells. Previously, limited studies investigated the complex relations among gene sets, but documents about their altering patterns across biological conditions still need to be prepared. In this study, we adopted and modified a classical k-nearest neighbor-based association function to detect inter-gene-set similarities.

Application of a mathematical model to clarify the statistical characteristics of a pan-tissue DNA methylation clock.

DNA methylation clocks estimate biological age based on DNA methylation profiles. This study developed a mathematical model to describe DNA methylation aging and the establishment of a pan-tissue DNA methylation clock. The model simulates the aging dynamics of DNA methylation profiles based on passive demethylation as well as the process of cross-sectional bulk data acquisition.

Plasma proteins as potential biomarkers of aging of single tissue and cell type.

Plasma proteins serve as biomarkers of aging and various age-related diseases. While a number of plasma proteins have been identified that increase or decrease with age, the interpretation of each protein is challenging. This is due to the nature of plasma, which is a mixture of factors secreted by many different tissues and cells.

Bioinformatic Identification of Potential RNA Alterations on the Atrial Fibrillation Remodeling from Human Pulmonary Veins.

Atrial fibrillation (AF) is the most frequent persistent arrhythmia. Many genes have been reported as a genetic background for AF. However, most transcriptome analyses of AF are limited to the atrial samples and have not been evaluated by multiple cardiac regions.

Data-driven identification and classification of nonlinear aging patterns reveals the landscape of associations between DNA methylation and aging.

Background: Aging affects the incidence of diseases such as cancer and dementia, so the development of biomarkers for aging is an important research topic in medical science. While such biomarkers have been mainly identified based on the assumption of a linear relationship between phenotypic parameters, including molecular markers, and chronological age, numerous nonlinear changes between markers and aging have been identified. However, the overall landscape of the patterns in nonlinear changes that exist in aging is unknown.

Mathematical model for the relationship between single-cell and bulk gene expression to clarify the interpretation of bulk gene expression data.

Background: Differential expression analysis is a standard approach in molecular biology. For example, genes whose expression levels differ between diseased and non-diseased samples are considered to be associated with that disease. On the other hand, differential variability analysis focuses on the differences of the variances of gene expression between sample groups.

Comparative Study of Transcriptome in the Hearts Isolated from Mice, Rats, and Humans.

The heart is a significant organ in mammalian life, and the heartbeat mechanism has been an essential focus of science. However, few studies have focused on species differences. Accordingly, challenges remain in studying genes that have universal functions across species and genes that determine species differences.

Novel insight into the correlation between hernia orifice of cystocele and lower urinary tract function: a pilot study.

Background: It has been hypothesized that women with significant pelvic organ prolapse (POP), particularly of the anterior vaginal wall, may have voiding dysfunction (VD). Although the VD mechanism due to cystocele is not fully understood, different vaginal compartments have rarely been closely examined. This study attempted to further elucidate the correlation between POP and VD through a new subgroup classification using cystoscopy.

Cell population-based framework of genetic epidemiology in the single-cell omics era.

Genetic epidemiology is a rapidly advancing field due to the recent availability of large amounts of omics data. In recent years, it has become possible to obtain omics information at the single-cell level, so genetic epidemiological models need to be updated to integrate with single-cell expression data. In this perspective paper, we propose a cell population-based framework for genetic epidemiology in the single-cell era.

Data-driven comparison of multiple high-dimensional single-cell expression profiles.

Comparing multiple single-cell expression datasets such as cytometry and scRNA-seq data between case and control donors provides information to elucidate the mechanisms of disease. We propose a completely data-driven computational biological method for this task. This overcomes the challenges of conventional cellular subset-based comparisons and facilitates further analyses such as machine learning and gene set analysis of single-cell expression datasets.

Recipient myeloperoxidase-producing cells regulate antibody-mediated acute versus chronic kidney allograft rejection.

Antibody-mediated rejection (ABMR) continues to be a major problem undermining the success of kidney transplantation. Acute ABMR of kidney grafts is characterized by neutrophil and monocyte margination in the tubular capillaries and by graft transcripts indicating NK cell activation, but the myeloid cell mechanisms required for acute ABMR have remained unclear. Dysregulated donor-specific antibody (DSA) responses with high antibody titers are induced in B6.

Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data.

Human immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the genetic factors that cause individual differences in whole lymphocyte profiles and their changes after vaccination without having to rely on biological assumptions, we performed a genome-wide association study (GWAS), using cytometry data.

Interpretation of omics data analyses.

Omics studies attempt to extract meaningful messages from large-scale and high-dimensional data sets by treating the data sets as a whole. The concept of treating data sets as a whole is important in every step of the data-handling procedures: the pre-processing step of data records, the step of statistical analyses and machine learning, translation of the outputs into human natural perceptions, and acceptance of the messages with uncertainty. In the pre-processing, the method by which to control the data quality and batch effects are discussed.

Decomposition of a set of distributions in extended exponential family form for distinguishing multiple oligo-dimensional marker expression profiles of single-cell populations and visualizing their dynamics.

Single-cell expression analysis is an effective tool for studying the dynamics of cell population profiles. However, the majority of statistical methods are applied to individual profiles and the methods for comparing multiple profiles simultaneously are limited. In this study, we propose a nonparametric statistical method, called Decomposition into Extended Exponential Family (DEEF), that embeds a set of single-cell expression profiles of several markers into a low-dimensional space and identifies the principal distributions that describe their heterogeneity.

Red cell distribution width predicts time to recurrence in patients with primary non-muscle-invasive bladder cancer and improves the accuracy of the EORTC scoring system.

Purpose: To investigate the clinical prognostic value of red cell distribution width (RDW) in patients with non-muscle-invasive bladder cancer (NMIBC).

Materials And Methods: We retrospectively evaluated 582 consecutive patients with primary NMIBC. The efficacy of preoperative RDW at predicting treatment outcome was assessed.

Effectiveness of Intravesical Doxorubicin Immediately Following Resection of Primary Non-muscle-invasive Bladder Cancer: A Propensity Score-matched Analysis.

Background: The purpose of this study was to investigate whether adding single immediate postoperative intravesical instillation of doxorubicin (SID) to transurethral resection of bladder tumor (TURBT) significantly reduced the risk of recurrence in patients with non-muscle-invasive bladder cancer (NMIBC).

Materials And Methods: We retrospectively analyzed the records of 720 patients diagnosed with primary NMIBC between 2002 through 2018 at the Kameda Medical Center. The primary outcome measure was time to recurrence.

Higher immunoglobulin A nephropathy recurrence in related-donor kidney transplants: The Japan Academic Consortium of Kidney Transplantation study.

Objective: To investigate the 10-year biopsy-proven recurrence rates and risk factors for immunoglobulin A nephropathy recurrence in kidney transplant recipients.

Methods: We included 299 kidney transplant recipients from 1995 to 2015, who had biopsy-proven underlying immunoglobulin A nephropathy and underwent zero-hour biopsy. The primary end-point was recurrence of immunoglobulin A nephropathy.