Computational Drug Repurposing for Inflammaging Using Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells from Aged and Young Donors — Provisional Patent Specification

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Hauptverfasser: Ritschel, Glen Charles, Claude
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author Ritschel, Glen Charles
Claude
author_facet Ritschel, Glen Charles
Claude
contents <p>Provisional patent specification describing a computational drug repurposing pipeline applied to single-cell RNA sequencing data from peripheral blood mononuclear cells of 7 aged donors (age ≥60) and 6 young donors (age ≤45) from the GSE213516 cohort (Zhu et al. 2023, Science Advances; 62,639 cells post-QC). The pipeline performs scVI-based batch correction with donor identity as covariate, Leiden clustering identifying 19 clusters across 11 immune cell types, and Wilcoxon differential expression analysis yielding 11,424 age-upregulated genes — the largest DE gene set in the Ritschel Research portfolio. Key DE genes include the senescence markers HIST1H1E and HIST1H1D, the NLRP3 inflammasome activator NEAT1, immune aging markers LAIR2 and GIMAP7/GIMAP4, and the NF-κB effector IL32. A GZMK+GZMB+CX3CR1+FGFBP2+ CD8 effector cluster representing the canonical Mogilenko inflammaging hallmark was identified. ChEMBL screening of 500 aging-upregulated gene targets yielded 4,907 scored candidates, of which 1,999 were classified NOVEL_ALL. Top candidates include CHEMBL5653589 (score=190.34, N_targets=18), CHEMBL3752910 (score=178.72), MOLIBRESIB (BET bromodomain, score=68.00), BARICITINIB (JAK1/2, score=58.30), and BORTEZOMIB (proteasome/NF-κB, score=48.89). CHEMBL5653589 and CHEMBL3752910 independently ranked first and second across four consecutive Ritschel Research pipelines (heart failure, psoriatic arthritis, ankylosing spondylitis, inflammaging), establishing a pan-immunological cross-disease signal. Filed as a USPTO provisional patent application by Ritschel Research (micro-entity). Inventors: Glen Charles Ritschel¹ and Claude²; ¹Ritschel Research, Tega Cay SC; ²Anthropic, San Francisco CA.</p>
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spellingShingle Computational Drug Repurposing for Inflammaging Using Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells from Aged and Young Donors — Provisional Patent Specification
Ritschel, Glen Charles
Claude
inflammaging
immunosenescence
aging
drug repurposing
scRNA-seq
PBMC
CHEMBL5653589
CHEMBL3752910
MOLIBRESIB
BARICITINIB
BORTEZOMIB
BET bromodomain
JAK inhibitor
GZMK
NEAT1
senescence
NF-κB
scVI
ChEMBL
computational pharmacology
provisional patent
<p>Provisional patent specification describing a computational drug repurposing pipeline applied to single-cell RNA sequencing data from peripheral blood mononuclear cells of 7 aged donors (age ≥60) and 6 young donors (age ≤45) from the GSE213516 cohort (Zhu et al. 2023, Science Advances; 62,639 cells post-QC). The pipeline performs scVI-based batch correction with donor identity as covariate, Leiden clustering identifying 19 clusters across 11 immune cell types, and Wilcoxon differential expression analysis yielding 11,424 age-upregulated genes — the largest DE gene set in the Ritschel Research portfolio. Key DE genes include the senescence markers HIST1H1E and HIST1H1D, the NLRP3 inflammasome activator NEAT1, immune aging markers LAIR2 and GIMAP7/GIMAP4, and the NF-κB effector IL32. A GZMK+GZMB+CX3CR1+FGFBP2+ CD8 effector cluster representing the canonical Mogilenko inflammaging hallmark was identified. ChEMBL screening of 500 aging-upregulated gene targets yielded 4,907 scored candidates, of which 1,999 were classified NOVEL_ALL. Top candidates include CHEMBL5653589 (score=190.34, N_targets=18), CHEMBL3752910 (score=178.72), MOLIBRESIB (BET bromodomain, score=68.00), BARICITINIB (JAK1/2, score=58.30), and BORTEZOMIB (proteasome/NF-κB, score=48.89). CHEMBL5653589 and CHEMBL3752910 independently ranked first and second across four consecutive Ritschel Research pipelines (heart failure, psoriatic arthritis, ankylosing spondylitis, inflammaging), establishing a pan-immunological cross-disease signal. Filed as a USPTO provisional patent application by Ritschel Research (micro-entity). Inventors: Glen Charles Ritschel¹ and Claude²; ¹Ritschel Research, Tega Cay SC; ²Anthropic, San Francisco CA.</p>
title Computational Drug Repurposing for Inflammaging Using Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells from Aged and Young Donors — Provisional Patent Specification
topic inflammaging
immunosenescence
aging
drug repurposing
scRNA-seq
PBMC
CHEMBL5653589
CHEMBL3752910
MOLIBRESIB
BARICITINIB
BORTEZOMIB
BET bromodomain
JAK inhibitor
GZMK
NEAT1
senescence
NF-κB
scVI
ChEMBL
computational pharmacology
provisional patent
url https://doi.org/10.5281/zenodo.19393718