Biology subjects

Matsubara, Y.

Publications and source records attributed to Matsubara, Y..

4 recordsLinked to original sources

bioRxiv2026

SPATNIC enables H&E-grounded cancer-cell identification across spatial and single-cell transcriptomic modalities in colorectal cancer

Tumors contain diverse non-cancer cells that constitute the tumor microenvironment; thus, identifying which cells are cancerous is a foundational and critical first step in cancer research. However, to our knowledge, no transcriptome-based classifier has been trained using pathologist-defined annotations from matched H&E images at single-cell resolution. Moreover, few tools can be shared across diverse platforms. Here, we present SPATNIC, a variational autoencoder that classifies individual cells as cancer or normal, trained on Xenium cells labeled by a pathologist review of matched H&E images. It matches or exceeds the performance of existing tools in primary colorectal tumors and liver and lung metastases. SPATNIC generalizes zero-shot across Visium, Visium HD, CosMx, Xenium, MERSCOPE, and single-cell RNA sequencing. In public single-cell atlases, it identified a rare POU2F3 tuft-like cancer stem cell population missed by existing annotations and associated with worse survival. In rectal cancer profiled before and after chemoradiotherapy, it separated cancer from normal epithelium in tissue, thus enabling per-patient screening of antibody-drug conjugate (ADC) targets.

cancer biology↗

bioRxiv2025

Human trust and emotion in the context of collision avoidance with an autonomous mobile robot: An investigation of predictability and smoothness in virtual reality

The integration of mobile robots into human environments requires that they behave in trustworthy ways. Trust develops through interaction, and erratic movements can easily break it. Previous research examined motion predictability and smoothness separately, but their combined effect remains unclear. We investigated how predictability (consistent versus random) and smoothness (gradual versus abrupt) influence human trust and emotion during collision avoidance in virtual reality. Twenty-six participants encountered a robot across repeated trials. We measured subjective valence, arousal, and trust, along with skin conductance responses. Predictability dominated the results. Consistent robot behavior led to increased trust and positive feelings over time. Conversely, unpredictable behavior kept trust low. Smoothness acted mainly as a moderator for arousal; smooth paths reduced the stress caused by unpredictable moves. We also found that prolonged proximity in gradual movements raised physiological arousal, even if users reported feeling calm. These findings suggest predictability drives social acceptance more than smoothness. In order to promote trust, robot designers should prioritize consistent, learnable behaviors. HighlightsO_LIWe examined AMR motion predictability and smoothness in VR collision avoidance. C_LIO_LIPredictable motion significantly improved human trust and valence over time. C_LIO_LIUnpredictable and abrupt behavior increased physiological arousal. C_LIO_LISmoothness modulated arousal primarily when behavior was unpredictable. C_LIO_LIPredictability is more critical than smoothness for social acceptance of AMRs. C_LI

neuroscience↗

bioRxiv2023

Exploring the genetic diversity of the Japanese Population: Insights from a Large-Scale Whole Genome Sequencing Analysis

The Japanese archipelago is a terminal location for human migration, and the contemporary Japanese people represent a unique population whose genomic diversity has been shaped by multiple migrations from Eurasia. Through high-coverage whole-genome sequencing (WGS) analysis of 9,850 samples from the National Center Biobank Network, we analyzed the genomic characteristics that define the genetic makeup of the modern Japanese population from a population genetics perspective. The dataset comprised populations from the Ryukyu Islands and other parts of the Japanese archipelago (Hondo). Low frequency detrimental or pathogenic variants were found in these populations. The Hondo population underwent two episodes of population decline during the Jomon period, corresponding to the Late Neolithic, and the Edo period, corresponding to the Early Modern era, while the Ryukyu population experienced a population decline during the shell midden period of the Late Neolithic in this region. Genes related to alcohol and lipid metabolism were affected by positive natural selection. Two genes related to alcohol metabolism were found to be 12,500 years out of phase with the time when they began to be affected by positive natural selection; this finding indicates that the genomic diversity of Japanese people has been shaped by events closely related to agriculture and food production. Author summaryThe human population in the Japanese archipelago exhibits significant genetic diversity, with the Ryukyu Islands and other parts of the archipelago (Hondo) having undergone distinct evolutionary paths that have contributed to the genetic divergence of the populations in each region. In this study, whole genome sequencing of healthy individuals from national research hospital biobanks was utilized to investigate the genetic diversity of the Japanese population. Haplotypes were inferred from the genomic data, and a thorough population genetic analysis was conducted. The results indicated not only genetic differentiation between Hondo and the Ryukyu Islands, but also marked differences in past population size. In addition, gene genealogies were inferred from the haplotypes, and the patterns were scrutinized for evidence of natural selection. This analysis revealed unique traces of natural selection in East Asian populations, many of which were believed to be linked to dietary changes brought about by agriculture and food production.

genomics↗

bioRxiv2018

The Desmosome is a Mesoscale Lipid Raft-Like Membrane Domain

Desmogleins are cadherin family adhesion molecules essential for epidermal integrity. Previous studies have shown that desmogleins associate with lipid rafts, but the significance of this association was not clear. Here, we report that the desmoglein transmembrane domain (TMD) is the primary determinant of raft association. Further, we identify a novel mutation in the DSG1 TMD (G562R) that causes severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome. Molecular modeling predicts that this G to R mutation shortens the DSG1 TMD, and experiments directly demonstrate that this mutation compromises both lipid raft association and desmosome incorporation. Finally, cryo-electron tomography (cryo-ET) indicates that the lipid bilayer within the desmosome is ~10% thicker than adjacent regions of the plasma membrane. These findings suggest that differences in bilayer thickness influence the organization of adhesion molecules within the epithelial plasma membrane, with cadherin TMDs recruited to the desmosome via establishment of a specialized mesoscale lipid raft-like membrane domain.

cell biology↗