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  <front>
    <journal-meta>
      <journal-id journal-id-type="iso-abbrev">Pharmacophore</journal-id>
      <journal-id journal-id-type="publisher-id">pharmacophorejournal.com</journal-id>
      <journal-id journal-id-type="publisher-id">Pharmacophore</journal-id>
      <journal-title-group>
        <journal-title>Pharmacophore</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2229-5402</issn>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">pharmacophorejournal.com-6995</article-id>
      <article-id pub-id-type="doi">10.51847/1ayMgZSKf4</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Precision Prescribing Under Unequal Genomic Representation: A Normative and Methodological Framework for Artificial Intelligence–Enabled Pharmacogenomics Across Ancestry, Polypharmacy, and Changing Clinical Contexts</article-title>
      </title-group>
                    <contrib-group>
                      <contrib contrib-type="author">
              <name>
                <surname>Kim</surname>
                <given-names>Daniel</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Wright</surname>
                <given-names>Emma</given-names>
              </name>
                              <xref rid="aff2" ref-type="aff">2</xref>
                                                            <xref rid="cor1" ref-type="corresp" />
                          </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Moretti</surname>
                <given-names>Luca</given-names>
              </name>
                              <xref rid="aff3" ref-type="aff">3</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Petrova</surname>
                <given-names>Elena</given-names>
              </name>
                              <xref rid="aff4" ref-type="aff">4</xref>
                                        </contrib>
                  </contrib-group>
                  <aff id="aff1">
            <label>1</label>Department of Pharmacogenomics and Precision Prescribing, Yonsei University, Seoul, South Korea.
          </aff>
                  <aff id="aff2">
            <label>2</label>Department of Clinical Pharmacology and Genomic Medicine, University of Edinburgh, Edinburgh, United Kingdom.
          </aff>
                  <aff id="aff3">
            <label>3</label>Department of Pharmaceutical Genomics and AI-Based Prescribing, University of Milan, Milan, Italy.
          </aff>
                  <aff id="aff4">
            <label>4</label>Department of Pharmacogenomics and Precision Therapeutics, Sofia University, Sofia, Bulgaria.
          </aff>
                          <author-notes>
            <corresp id="cor1">
              <bold>Address for correspondence:</bold> Prof. Wael Abu Dayyih, Department of
              Pharmaceutical Chemistry, Faculty of Pharmacy, Mutah University, Al-Karak 61710, Jordan.
                              E-mail: <email xlink:href="emma.wright@ed.ac.uk">emma.wright@ed.ac.uk</email>
                          </corresp>
          </author-notes>
                    <pub-date pub-type="epub">
        <day>28</day>
        <month>10</month>
        <year>2026</year>
      </pub-date>
      <volume>17</volume>
      <issue>5</issue>
      <fpage>121</fpage>
      <lpage>129</lpage>
      <permissions>
        <copyright-statement>
          Copyright: &#x000a9; 2026 Pharmacophore
        </copyright-statement>
        <copyright-year>2026</copyright-year>
        <license>
          <ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/"
            specific-use="textmining" content-type="ccbyncsalicense">
            https://creativecommons.org/licenses/by-nc-sa/4.0/</ali:license_ref>
          <license-p>This is an open access journal, and articles are distributed under the terms of
            the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows
            others to remix, tweak, and build upon the work non-commercially, as long as appropriate
            credit is given and the new creations are licensed under the identical terms.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>A<sc>BSTRACT</sc></title>
        <p>Artificial intelligence–enabled pharmacogenomics promises to extend precision prescribing by integrating genomic variation with increasingly rich clinical information. Its validity, however, depends on more than predictive performance. Pharmacogenomic evidence has been generated from populations, variant catalogs, assays, and implementation environments that differ substantially in genomic representation, while the clinical meaning of genotype may change as co-medications, disease state, organ function, and treatment history alter drug exposure and phenotype. This article develops a normative and methodological account of precision prescribing under these conditions. It separates population representation from individual ancestry inference, ancestry from race, germline genotype from current metabolic phenotype, and prediction from clinical action. Unequal genomic representation is treated as an evidentiary problem that affects which variants are discovered, characterized, measured, and validated, whereas polypharmacy and changing clinical context are treated as interpretation problems that can modify the translation from genotype to expected drug response. The resulting argument is that representation-aware pharmacogenomic systems require explicit evidence provenance, patient-level genomic characterization, context-sensitive phenotype updating, uncertainty handling, and safeguards against extrapolation beyond adequately characterized populations. Equity therefore cannot be evaluated only after deployment or reduced to average predictive parity.  It must be considered across evidence generation, variant interpretation, clinical decision support, monitoring, and the distribution of uncertainty itself. . A representation-aware approach can strengthen AI-enabled pharmacogenomic prescribing only when ancestry, genomic variation, medication context, and clinical change remain analytically distinct and are recombined at the point of individual treatment decision.</p>
      </abstract>
      <kwd-group>
                <kwd>: Pharmacogenomics</kwd>
                <kwd>Genomic representation</kwd>
                <kwd>Genetic ancestry</kwd>
                <kwd>Polypharmacy</kwd>
                <kwd>Phenoconversion</kwd>
                <kwd>Precision prescribing</kwd>
              </kwd-group>
    </article-meta>
  </front>
</article>
