Most of the current alternative splicing (AS) analysis tools are powerless to analyse complex splicing. To address this, we developed SUVA (Splice sites Usage Variation Analysis) that decomposes complex splicing events into five types of splice junction pairs. By analysing real and simulated data, SUVA showed higher sensitivity and accuracy in detecting AS events than the compared methods. Notably, SUVA detected extensive complex AS events and screened out 69 highly conserved and dominant AS events associated with cancer. The cancer-associated complex AS events in FN1 and the co-regulated RNA-binding proteins were significantly correlated with patient survival.
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http://dx.doi.org/10.1080/15476286.2021.1940037 | DOI Listing |
Int J Mol Sci
December 2024
Moores Cancer Center, University of California San Diego, San Diego, CA 92037, USA.
The discovery of tumor-derived neoantigens which elicit an immune response through major histocompatibility complex (MHC-I/II) binding has led to significant advancements in immunotherapy. While many neoantigens have been discovered through the identification of non-synonymous mutations, the rate of these is low in some cancers, including head and neck squamous cell carcinoma. Therefore, the identification of neoantigens through additional means, such as aberrant splicing, is necessary.
View Article and Find Full Text PDFExp Hematol
January 2025
Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. Electronic address:
T-cell acute lymphoblastic leukemia (T-ALL), which constitutes of 10-15% of all pediatric ALL cases, is known for its complex pathology due to pervasive genetic and chromosomal abnormalities. Although most children are successfully cured, chromosomal rearrangements involving the KMT2A gene is considered a poor prognostic factor. In a cohort of 171 pediatric T-ALL samples we have studied differences in gene and splice variant patterns in KMT2A rearranged (KMT2A-r) T-ALL compared to KMT2A negative (KMT2A-wt) T-ALL samples.
View Article and Find Full Text PDFProteomics
January 2025
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Alzheimer's disease (AD) is a leading cause of dementia, but the pathogenesis mechanism is still elusive. Advances in proteomics have uncovered key molecular mechanisms underlying AD, revealing a complex network of dysregulated pathways, including amyloid metabolism, tau pathology, apolipoprotein E (APOE), protein degradation, neuroinflammation, RNA splicing, metabolic dysregulation, and cognitive resilience. This review examines recent proteomic findings from AD brain tissues and biological fluids, highlighting potential biomarkers and therapeutic targets.
View Article and Find Full Text PDFRespir Investig
January 2025
Department of Anesthesiology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, 215004, China. Electronic address:
Background: The mechanism underlying necroptosis in pulmonary vessel endothelial cells (PVECs) resulting from long non-coding RNA (lncRNA)-induced alternative splicing (AS) of target genes in acute lung injury (ALI) remains unclear.
Methods: Lipopolysaccharide (LPS)-induced expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and lncRNAs was analyzed via RT-PCR in PVECs. Full-transcriptome sequencing was used to detect AS-related mRNAs.
Curr Opin Struct Biol
January 2025
Sorbonne Université, CNRS, IBPS, Laboratory of Computational and Quantitative Biology (LCQB), UMR 7238, 75005 Paris, France.
The mRNA splicing machinery has been estimated to generate 100,000 known protein-coding transcripts for 20,000 human genes (Ensembl, Sept. 2024). However, this set is expanding with the massive and rapidly growing data coming from high-throughput technologies, particularly single-cell and long-read sequencing.
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