Ontology Specific Alternative Splicing Changes in Alzheimer's Disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35774499", "kind": "science-record", "revision": 4, "content_hash": "sha256:0e5782602a1a49bfb35dda96c97963dd67d97d4bd7d4ac6da5d7c39009465cfd", "created_at": "2026-11-01T18:14:48Z", "updated_at": "2026-11-01T22:06:55Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Ontology Specific Alternative Splicing Changes in Alzheimer's Disease.", "doi": "10.3389/fgene.2022.926049", "pmid": "35774499", "authors": ["Yanjun Lu", "Daoyuan Yue", "Jiazhao Xie", "Liming Cheng", "Xiong Wang"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Alternative splicing (AS) is a common phenomenon and correlates with aging and aging-related disorders including Alzheimer's disease (AD). We aimed to systematically characterize AS changes in the cerebral cortex of 9-month-old APP/PS1 mice. The GSE132177 dataset was downloaded from GEO and ENA databases, aligned to the GRCm39 reference genome from ENSEMBL via STAR. Alternative 3'SS (A3SS), alternative 5'SS (A5SS), skipped exon (SE), retained intron (RI), and mutually exclusive exons (MXE) AS events were evaluated using rMATS, rmats2sashimiplot, and maser. Differential genes or transcripts were analyzed using the limma R package. Gene ontology analysis was performed with the clusterProfiler R package. A total of 60,705 raw counts of AS were identified, and 113 significant AS events were finally selected in accordance with the selection criteria: 1) average coverage >10 and 2) delta percent spliced in (ΔPSI) >0.1. SE was the most abundant AS event (61.95%), and RI was the second most abundant AS type (13.27%), followed by A3SS (12.39%), thereafter A5SS and MXE comprised of 12.39%. Interestingly, genes that experienced SE were enriched in histone acetyltransferase (HAT) complex, while genes spliced by RI were enriched in autophagy and those which experienced A3SS were enriched in methyltransferase activity revealed by GO analysis. In conclusion, we revealed ontology specific AS changes in AD. Our analysis provides novel pathological mechanisms of AD.", "claims": [{"id": "claim-method", "statement": "The aligned and sorted bam files after STAR alignment was used for AS analysis using rMATS (v4.1.2) and rmats2sashimiplot (v2.0.4) (Shen et al., 2014). A3SS, A5SS, SE, RI, and MXE events were evaluated. Significant AS events were identified with the following criteria (Wilkinson et al., 2020): average coverage >10 (Leung et al., 2011); delta percent spliced in (ΔPSI) >0.1. The AS event statistics were performed using maser (v1.12.1) and rtracklayer (v1.54.0) R packages, and the results were plotted using echarts4r (v0.4.3), maser, and ggplot2 (v3.3.5) R packages.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35774499", "locator": "sections[7] \"Alternative Splicing Analysis\" paragraph 2", "quote": "The aligned and sorted bam files after STAR alignment was used for AS analysis using rMATS (v4.1.2) and rmats2sashimiplot (v2.0.4) (Shen et al., 2014). A3SS, A5SS, SE, RI, and MXE events were evaluated. Significant AS events were identified with the following criteria (Wilkinson et al., 2020): average coverage >10 (Leung et al., 2011); delta percent spliced in (ΔPSI) >0.1. The AS event statistics were performed using maser (v1.12.1) and rtracklayer (v1.54.0) R packages, and the results were plotted using echarts4r (v0.4.3), maser, and ggplot2 (v3.3.5) R packages."}], "state": "complete"}, {"id": "claim-data-access", "statement": "A publicly available dataset (GSE132177) submitted by Jun Wan and Nana Ma (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE132177) was used in this study. The code of this study was written by our team and was deposited in Github (https://github.com/tjhwangxiong/AD-GSE132177-Alternative-Splicing-pipeline).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35774499", "locator": "sections[18] \"Data Availability Statement\" paragraph 2", "quote": "A publicly available dataset (GSE132177) submitted by Jun Wan and Nana Ma (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE132177) was used in this study. The code of this study was written by our team and was deposited in Github (https://github.com/tjhwangxiong/AD-GSE132177-Alternative-Splicing-pipeline)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The analysis identified 113 significant alternative-splicing events in the cerebral cortex of 9-month-old APP/PS1 mice.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35774499", "locator": "sections[10] \"Global Summary of Alternative Splicing Events\" paragraph 2", "quote": "Eventually, 113 significant AS events were collected according to our strict criteria (average coverage >10, ΔPSI >0.1) (Figure 1B; Table 1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The analysis identified 113 significant alternative-splicing events in the cerebral cortex of 9-month-old APP/PS1 mice.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35774499"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE132177"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE132177"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35774499", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2022.926049", "sha256": "sha256:711c8493ba5bb7c80ce35bf28cb1aab787f11985e878e6dbeeedc715cbfec8e5", "bytes": 29585, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2022.926049", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9237535", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE132177", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE132177", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE132177", "version": null, "note": "A publicly available dataset (GSE132177) submitted by Jun Wan and Nana Ma (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE132177) was used in this study. 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