{
  "abstract": "Human PTGS1 and PTGS2 encode cyclooxygenase paralogs that regulate prostaglandin biosynthesis and are major targets of nonsteroidal anti-inflammatory drugs (NSAIDs). Interpreting population-differentiated PTGS variation requires integration of allele-frequency structure with transcript consequence, protein topology, splice-prediction evidence and structural context. This study integrated allele-resolved population differentiation, transcript-aware consequence annotation, splice-prediction boundary checks, protein-domain mapping, direct leader-sequence property calculations and controlled structural analyses. Candidate classes distinguished high-FST synonymous contextual markers, N-terminal PTGS1 leader-sequence missense variants, splice-region candidates and PTGS2 p.Val511Ala. Web-based SpliceAI/Pangolin evaluation of seven splice-relevant or comparator variants provided limited support for splice alteration. A retrospective comparison of 31 missense candidates showed that Val511Ala was not the most differentiated missense variant overall, but ranked first by allele frequency, allele-frequency range and maximum pairwise FST within four channel-context candidates; FST was used only to describe population differentiation. Canonical Val511 mapped to 5KIR Val525, a second-shell position adjacent to the rofecoxib-contact network. Controlled docking-score, contact and direct-frame pose analyses detected no systematic variant-associated shift under the tested conditions. PTGS1 p.Trp8Arg and p.Pro17Leu produced distinct directly calculated changes in net-charge proxy, hydrophobic-residue count, mean Kyte-Doolittle hydropathy, aromatic-residue count and proline count across the 23-residue leader sequence and descriptive H-region. No signal-peptide predictor output was used, and effects on SRP recognition, ER targeting, translocation, cleavage, membrane insertion, maturation, abundance, localization, enzyme activity or drug response were not demonstrated. These results support a calibrated prioritisation framework in which population differentiation identifies structured variation, while transcript consequence, protein context and reproducible quantitative analyses define experimentally testable candidates.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Microbiology and Parasitology, Faculty of Medicine, St. Francis University College of Health and Allied Sciences (SFUCHAS), Ifakara, Tanzania"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Reuben S. Maghembe"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/36rppeey10xbt.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0358222",
  "fulltext_url": null,
  "id": "36rppeey10xbt",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0358222",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "3004|Pharmacogenetics and Drug Metabolism"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Amino acids/Cyclic amino acids/Proline"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Protein structure/Protein structure comparison"
    ],
    [
      "plos",
      "/Biology and life sciences/Bioengineering/Biotechnology/Pharmacogenomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Computational biology/Genome analysis/Genome annotation"
    ],
    [
      "plos",
      "/Biology and life sciences/Ecology/Ecological metrics/Species diversity"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genome analysis/Genome annotation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genomic medicine/Pharmacogenomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Macromolecular structure analysis/Protein structure/Protein structure comparison"
    ],
    [
      "plos",
      "/Computer and information sciences/Information theory/Channel coding"
    ],
    [
      "plos",
      "/Ecology and environmental sciences/Ecology/Ecological metrics/Species diversity"
    ],
    [
      "plos",
      "/Engineering and technology/Bioengineering/Biotechnology/Pharmacogenomics"
    ],
    [
      "plos",
      "/Engineering and technology/Electronics engineering/Electronics/Comparators"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pain management/Analgesics/NSAIDs"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pharmacology/Drugs/Analgesics/NSAIDs"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pharmacology/Pharmacogenomics"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Chemical compounds/Organic compounds/Amino acids/Cyclic amino acids/Proline"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Organic chemistry/Organic compounds/Amino acids/Cyclic amino acids/Proline"
    ]
  ],
  "openalex": "W7214379726",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358222&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/36rppeey10xbt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pone.0358222",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0358222"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:ecology",
      "subfield": "ecology"
    },
    {
      "field": "biology",
      "origin": "plos:genomics",
      "subfield": "genetics-genomics"
    },
    {
      "field": "biology",
      "origin": "plos:biotechnology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Comparative evolutionary pharmacogenomics of human prostaglandin-endoperoxide synthase paralogs identifies population-structured coding variation and protein-contextual candidates in N-terminal leader-sequence and catalytic-channel regions",
  "title_text": "Comparative evolutionary pharmacogenomics of human prostaglandin-endoperoxide synthase paralogs identifies population-structured coding variation and protein-contextual candidates in N-terminal leader-sequence and catalytic-channel regions",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/36rppeey10xbt",
  "venue": "PLOS One",
  "versions": []
}