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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-6970</article-id>
      <article-id pub-id-type="doi">10.51847/eBSEQIBYbb</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Cell State, Not Cell Type, Should Anchor Computational Strategies for Therapeutic Target Discovery</article-title>
      </title-group>
                    <contrib-group>
                      <contrib contrib-type="author">
              <name>
                <surname>Hamdy</surname>
                <given-names>Ahmed</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                                            <xref rid="cor1" ref-type="corresp" />
                          </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Khalil</surname>
                <given-names>Mona</given-names>
              </name>
                              <xref rid="aff2" ref-type="aff">2</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Ibrahim</surname>
                <given-names>Youssef</given-names>
              </name>
                              <xref rid="aff3" ref-type="aff">3</xref>
                                        </contrib>
                  </contrib-group>
                  <aff id="aff1">
            <label>1</label>Department of Cell State-Driven Target Discovery, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
          </aff>
                  <aff id="aff2">
            <label>2</label>Department of Computational Strategies for Cell States, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
          </aff>
                  <aff id="aff3">
            <label>3</label>Department of Beyond-Cell-Type Target Discovery, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
          </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="ahmed.hamdy@cu.edu.eg">ahmed.hamdy@cu.edu.eg</email>
                          </corresp>
          </author-notes>
                    <pub-date pub-type="epub">
        <day>28</day>
        <month>02</month>
        <year>2025</year>
      </pub-date>
      <volume>16</volume>
      <issue>1</issue>
      <fpage>50</fpage>
      <lpage>60</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>Single-cell technologies have increased the resolution at which disease biology can be examined, yet computational target-discovery strategies still frequently treat cell type as the principal biological unit. This practice can obscure therapeutically important variation because cells assigned to the same lineage may occupy divergent activation, differentiation, stress, resistance, or disease-associated states. The unresolved problem is therefore not simply how to classify cells more accurately, but how to determine which state-dependent molecular relationships are sufficiently reproducible, mechanistically credible, and contextually bounded to support therapeutic hypotheses. This theory article proposes State-Anchored Target Discovery as a conceptual framework for organizing such evidence. The proposed construct represents a candidate target through a state–transition–context relationship: the cellular state in which the target is implicated, the disease- or treatment-associated transition it may influence, and the biological context within which the relationship is expected to hold. It further separates state markers from causal regulators, distinguishes predicted trajectories from experimentally confirmed transitions, and treats annotation uncertainty, cross-cohort replication, and perturbational evidence as integral parts of the target claim rather than downstream technical checks. The central contribution is an evidence architecture that connects single-cell heterogeneity to target prioritization and patient-stratification hypotheses without reducing scientific adequacy to a single clustering, integration, prediction, or benchmark measure. The construct remains theoretical. It cannot establish causality, druggability, safety, developability, clinical utility, or regulatory acceptability without additional experimental and pharmaceutical evidence. Its value lies in defining a more precise analytical object for therapeutic target discovery and in clarifying the validation boundaries that should govern state-centered computational claims.</p>
      </abstract>
      <kwd-group>
                <kwd>Single-cell transcriptomics</kwd>
                <kwd>Cell states</kwd>
                <kwd>Therapeutic target discovery</kwd>
                <kwd>Disease-associated transitions</kwd>
                <kwd>Cellular plasticity</kwd>
                <kwd>Perturbational evidence</kwd>
              </kwd-group>
    </article-meta>
  </front>
</article>