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  <front>
    <journal-meta>
      <journal-title-group>
        <journal-title>Cosmological and Astrobiological Review</journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0000-0000</issn>
      <issn pub-type="epub">0000-0000</issn>
      <publisher>
        <publisher-name>SAPCRAA</publisher-name>
        <publisher-loc>Banja Luka, Bosnia and Herzegovina</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">1521</article-id>
      <article-id pub-id-type="doi">https://doi.org/10.65932/CAR-2024-1-4</article-id>
      <title-group>
        <article-title>The human pangenome and the end of the singlereference paradigm: t2t-chm13, hprc, and the parti framework for adoption-readiness evaluation</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Markovski</surname>
            <given-names>Teodor</given-names>
          </name>
          <contrib-id contrib-id-type="orcid">https://orcid.org/0009-0000-2260-8023</contrib-id>
        </contrib>
      </contrib-group>
      <pub-date pub-type="epub">
        <day>30</day>
        <month>12</month>
        <year>2024</year>
      </pub-date>
      <volume>2</volume>
      <issue>1</issue>
      <fpage>46</fpage>
      <lpage>56</lpage>
      <self-uri xlink:href="https://www.sapcraa.com/article-preview/1521"/>
      <abstract>
        <p>The publication of the telomere-to-telomere CHM13 sequence (Nurk et al., 2022) and the first draft Human Pangenome Reference (Liao et al., 2023) jointly mark the end of the linear single-reference paradigm that has governed human genomics for two decades. GRCh38 omits roughly 200 megabases of repetitive and acrocentric sequence and carries a documented European-ancestry bias; the new resources close most of that gap and reframe the reference itself as a structured graph over 47 phased haplotypes spanning multiple ancestry groups. This article addresses a question that the celebratory tone of the original announcements largely sidestepped: how mature is the actual transition? We propose the Pangenome Adoption-Readiness Transition Index (PARTI), a normalized composite metric on [0,1] that aggregates five dimensions of practical readiness — reference completeness gain (D_comp), population and ancestry representation (D_pop), toolchain native-graph support (D_tool), clinical-pipeline integration (D_clin), and variant-call equivalence relative to legacy reference workflows (D_eq) — into a single comparable score via geometric mean. PARTI is applied to five canonical use-cases: germline short-variant calling, structural-variant detection, repeat-rich and segmental-duplication analysis, pharmacogenomic interpretation, and clinical diagnostic pipelines for rare disease and oncology. Resulting scores range from 0.62 (structural-variant detection, the largest immediate win) down to 0.21 (clinical diagnostic pipelines, the slowest mover). The analysis identifies clinical-pipeline integration (D_clin) as the binding constraint across four of five use-cases: graphnative variant callers exist, but the regulatory, interpretive, and infrastructure layers — variant databases, ACMG/AMP guideline operationalization on a graph reference, electronic-healthrecord liftover, and laboratory information-management-system compatibility — remain calibrated to GRCh38. PARTI thus reframes the transition as a stratified engineering and policy problem rather than an undifferentiated paradigm shift, and identifies the specific subsystems on which the practical end of the single-reference paradigm is contingent.</p>
      </abstract>
      <kwd-group kwd-group-type="author">
        <kwd>human pangenome</kwd>
        <kwd>T2T-CHM13</kwd>
        <kwd>Human Pangenome Reference Consortium</kwd>
        <kwd>reference genome</kwd>
        <kwd>variant calling; structural variation</kwd>
        <kwd>pangenome graphs</kwd>
        <kwd>PARTI index</kwd>
      </kwd-group>
    </article-meta>
  </front>
</article>
