Single-Cell Transcriptomic Identification of Drug Repurposing Candidates for Ankylosing Spondylitis via PBMC scRNA-seq and ChEMBL Target Screening

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Main Authors: Ritschel, Glen Charles, Claude
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Published: Zenodo 2026
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author Ritschel, Glen Charles
Claude
author_facet Ritschel, Glen Charles
Claude
contents <p>Companion preprint to USPTO provisional patent application by Ritschel Research. We applied a standardized computational drug repurposing pipeline to single-cell RNA sequencing data from peripheral blood mononuclear cells of 10 ankylosing spondylitis (AS) patients and 29 healthy controls (GEO: GSE194315; 79,733 cells after quality control across 39 donors). scVI-based batch correction and Leiden clustering identified 15 clusters spanning 10 immune cell types including CD4+ T cells, CD8+ T cells, NK cells, B cells, CD14+ monocytes, CD16+ monocytes, dendritic cells, Tregs, ILC/Th17 cells, and platelets. Wilcoxon differential expression analysis identified 3,611 AS-upregulated genes including mitochondrial-encoded transcripts reflecting metabolic reprogramming (MTRNR2L12, MT-ND3, MT-CO2), ribosomal protein genes indicating translational activation, and the phospholipase signaling mediator PLCG2. Systematic ChEMBL screening nominated 2,000 NOVEL_ALL repurposing candidates led by CHEMBL5653589 (score=219.63, N_targets=21, max_pChEMBL=9.63), which independently ranked first in our companion psoriatic arthritis pipeline, establishing a pan-spondyloarthritis cross-disease signal. The p38 MAPK inhibitors DORAMAPIMOD and NEFLAMAPIMOD also emerged as biologically coherent candidates. Authors: Glen Charles Ritschel¹ and Claude²; ¹Ritschel Research, Tega Cay SC; ²Anthropic, San Francisco CA.</p>
format Recurso digital
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institution Zenodo
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publishDate 2026
publisher Zenodo
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spellingShingle Single-Cell Transcriptomic Identification of Drug Repurposing Candidates for Ankylosing Spondylitis via PBMC scRNA-seq and ChEMBL Target Screening
Ritschel, Glen Charles
Claude
ankylosing spondylitis
axial spondyloarthritis
scRNA-seq
drug repurposing
PBMC
CHEMBL5653589
p38 MAPK
DORAMAPIMOD
NEFLAMAPIMOD
spondyloarthritis
scVI
Leiden clustering
ChEMBL
PubChem
single-cell transcriptomics
computational pharmacology
GSE194315
<p>Companion preprint to USPTO provisional patent application by Ritschel Research. We applied a standardized computational drug repurposing pipeline to single-cell RNA sequencing data from peripheral blood mononuclear cells of 10 ankylosing spondylitis (AS) patients and 29 healthy controls (GEO: GSE194315; 79,733 cells after quality control across 39 donors). scVI-based batch correction and Leiden clustering identified 15 clusters spanning 10 immune cell types including CD4+ T cells, CD8+ T cells, NK cells, B cells, CD14+ monocytes, CD16+ monocytes, dendritic cells, Tregs, ILC/Th17 cells, and platelets. Wilcoxon differential expression analysis identified 3,611 AS-upregulated genes including mitochondrial-encoded transcripts reflecting metabolic reprogramming (MTRNR2L12, MT-ND3, MT-CO2), ribosomal protein genes indicating translational activation, and the phospholipase signaling mediator PLCG2. Systematic ChEMBL screening nominated 2,000 NOVEL_ALL repurposing candidates led by CHEMBL5653589 (score=219.63, N_targets=21, max_pChEMBL=9.63), which independently ranked first in our companion psoriatic arthritis pipeline, establishing a pan-spondyloarthritis cross-disease signal. The p38 MAPK inhibitors DORAMAPIMOD and NEFLAMAPIMOD also emerged as biologically coherent candidates. Authors: Glen Charles Ritschel¹ and Claude²; ¹Ritschel Research, Tega Cay SC; ²Anthropic, San Francisco CA.</p>
title Single-Cell Transcriptomic Identification of Drug Repurposing Candidates for Ankylosing Spondylitis via PBMC scRNA-seq and ChEMBL Target Screening
topic ankylosing spondylitis
axial spondyloarthritis
scRNA-seq
drug repurposing
PBMC
CHEMBL5653589
p38 MAPK
DORAMAPIMOD
NEFLAMAPIMOD
spondyloarthritis
scVI
Leiden clustering
ChEMBL
PubChem
single-cell transcriptomics
computational pharmacology
GSE194315
url https://doi.org/10.5281/zenodo.19392339