Integration of accumulative large-scale single-cell transcriptomes requires scalable batch-correction approaches. Here we propose Fugue, a simple and efficient batch-correction method that is scalable for integrating super large-scale single-cell transcriptomes from diverse sources. The core idea of the method is to encode batch information as trainable parameters and add it to single-cell expression profile; subsequently, a contrastive learning approach is used to learn feature representation of the additive expression profile. We demonstrate the scalability of Fugue by integrating all single cells obtained from the Human Cell Atlas. We benchmark Fugue against current state-of-the-art methods and show that Fugue consistently achieves improved performance in terms of data alignment and clustering preservation. Our study will facilitate the integration of single-cell transcriptomes at increasingly large scale.
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http://dx.doi.org/10.1093/bib/bbac327 | DOI Listing |
Geroscience
January 2025
Buck Institute for Research On Aging, Novato, CA, 94945, USA.
Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood.
View Article and Find Full Text PDFGenome Biol
January 2025
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Background: Genetic studies have associated thousands of enhancers with breast cancer (BC). However, the vast majority have not been functionally characterized. Thus, it remains unclear how BC-associated enhancers contribute to cancer.
View Article and Find Full Text PDFGenome Med
January 2025
Department of Systems Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
Background: Despite extensive analysis, the dynamic changes in prostate epithelial cell states during tissue homeostasis as well as tumor initiation and progression have been poorly characterized. However, recent advances in single-cell RNA-sequencing (scRNA-seq) technology have greatly facilitated studies of cell states and plasticity in tissue maintenance and cancer, including in the prostate.
Methods: We have performed meta-analyses of new and previously published scRNA-seq datasets for mouse and human prostate tissues to identify and compare cell populations across datasets in a uniform manner.
Mol Cancer
January 2025
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Background And Aims: Oncogenic KRAS mutations are present in approximately 90% of pancreatic ductal adenocarcinoma (PDAC). However, Kras mutation alone is insufficient to transform precancerous cells into metastatic PDAC. This study investigates how KRAS-mutated epithelial cells acquire the capacity to escape senescence or even immune clearance, thereby progressing to advanced PDAC.
View Article and Find Full Text PDFCell Biol Toxicol
January 2025
Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, No.555 Friendship East Road, South Gate, Beilin District, Xi'an, 710054, Shaanxi, China.
This study delved into the molecular mechanisms underlying mechanical stress-induced intervertebral disc degeneration (msi-IDD) through single-cell and high-throughput transcriptome sequencing in mouse models and patient samples. Results exhibited an upsurge in macrophage presence in msi-IDD intervertebral disc (IVD) tissues, with secreted phosphoprotein 1 (SPP1) identified as a pivotal driver exacerbating degeneration via the protein kinase RNA-like endoplasmic reticulum kinase/ activating transcription factor 4/ interleukin-10 (PERK/ATF4/IL-10) signaling axis. Inhibition of SPP1 demonstrated promising outcomes in mitigating msi-IDD progression in both in vitro and in vivo models.
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