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Transient surges in gene or protein expression often mark the key regulatory checkpoints that propel cells from one functional state to the next, yet they are easy to miss in sparse, noisy single‑cell omics data. We introduce , a trajectory‑inference pipeline integrated into our cloud‑based single‑cell analysis platform PSCS. scTransient transforms single‑cell expression profiles into continuous pseudotime signals and couples them with wavelet‑based signal processing to isolate short‑lived but biologically meaningful bursts of activity. After ordering cells with unsupervised graph trajectories or supervised psupertime, windows expression values along pseudotime, applies a continuous wavelet transform, and assigns every gene a Transient‑Event Score (TES) that rewards sharp, isolated coefficients while penalizing background fluctuations. Synthetic benchmarks show TES robustly recovers transient events across a wide range of cell numbers, signal‑to‑noise ratios, and event widths. Applying scTransient to three public datasets-hematopoietic differentiation, monocyte‑to‑macrophage maturation, and single‑cell proteomic cell‑cycle progression-uncovers previously unreported, process‑specific expression spikes. These include erythropoiesis regulators (e.g., Nfe2), membrane‑raft remodeling proteins during macrophage differentiation, and S‑phase DNA‑replication factors in A549 cells. Functional enrichment confirms that top‑scoring genes cluster into pathways directly pertinent to each transition. By extending trajectory inference from descriptive ordering to quantitative detection of fleeting regulatory programs, scTransient-now readily accessible via the PSCS web interface-offers researchers a practical route to uncovering transient molecular events that drive development, differentiation, and disease.
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http://dx.doi.org/10.1101/2025.05.07.652753 | DOI Listing |
J Chem Inf Model
September 2025
College of Agriculture and Biological Science, Dali University, Dali 671000, China.
The E76K mutation in protein tyrosine phosphatase (PTP) SHP2 is a recurrent driver of developmental disorders and cancers, yet the mechanism by which this single-site substitution promotes persistent activation remains elusive. Here, we combine path-based conformational sampling, unbiased molecular dynamics (MD) simulations, Markov state models (MSMs), and neural relational inference (NRI) to elucidate how E76K reshapes the activation landscape and regulatory architecture of SHP2. Using a minimum-action trajectory derived from experimentally determined closed and open structures, we generated representative transition intermediates to guide the unbiased MD simulations.
View Article and Find Full Text PDFFront Immunol
September 2025
Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Intrinsic genetic alterations and dynamic transcriptional changes contribute to the heterogeneity of solid tumors. Lung adenocarcinoma (LUAD) is characterized by its significant histological, cellular and molecular heterogeneity. The present study aimed to study the spatial transcriptomics of primary LUAD with initial hopes to decipher molecular characteristics of subtype transitions in LUAD progression, offering new insights for novel therapeutic strategies.
View Article and Find Full Text PDFExp Cell Res
September 2025
Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong 510080, China. Electronic address:
Background: Chronic rejection is a major cause of long-term kidney allograft failure, characterized by persistent inflammation and progressive fibrosis. Macrophages are central mediators of this process, but their phenotypic heterogeneity and regulatory mechanisms in chronic rejection remain incompletely understood.
Methods: We performed single-cell transcriptomic analysis on renal allograft biopsies from patients with different types of rejection and on a time-course rat model of chronic rejection.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
August 2025
Research Center for Sport Ability Assessment and Enhancement, Northeast Normal University, Changchun 130024, China.
To propose a functional method for locating the shoulder joint center of rotation aimed at rapid estimation of the upper limb reachable domain envelope, thereby informing ergonomic design and task optimization. In March 2024, shoulder kinematics during gait were recorded from ten adults using a three-dimensional motion-capture system. Assuming the existence of a point near the glenohumeral joint that maintains a fixed spatial relationship to the humerus and the acromion, we estimated both static and dynamic centers of rotation.
View Article and Find Full Text PDFInt Immunopharmacol
September 2025
The First Affiliated Hospital, Zhejiang University School of Medicine, 1367 West Wenyi Rd., Yuhang District, Hangzhou, Zhejiang Province, China. Electronic address:
Macrophages, pivotal orchestrators of the immune system, are integral to the initiation of specific immune responses and exert profound influence on the pathogenesis, progression, and therapeutic landscape of aortic dissection (AD). Leveraging the precision of single-cell RNA sequencing (scRNA-seq), this study aimed to dissect the heterogeneity of macrophages within the AD microenvironment. We identified a unique macrophage subpopulation, termed AD-associated macrophages (AD-mac), which is predominantly implicated in the early stages of AD pathogenesis.
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