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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">JDS</journal-id>
<journal-title-group><journal-title>Journal of Data Science</journal-title></journal-title-group>
<issn pub-type="epub">1683-8602</issn><issn pub-type="ppub">1680-743X</issn><issn-l>1680-743X</issn-l>
<publisher>
<publisher-name>School of Statistics, Renmin University of China</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">JDS1170</article-id>
<article-id pub-id-type="doi">10.6339/25-JDS1170</article-id>
<article-categories><subj-group subj-group-type="heading">
<subject>Statistical Data Science</subject></subj-group></article-categories>
<title-group>
<article-title>EMixed: Probabilistic Multi-Omics Cellular Deconvolution of Bulk Omics Data</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Cai</surname><given-names>Manqi</given-names></name><xref ref-type="aff" rid="j_jds1170_aff_001">1</xref><xref ref-type="fn" rid="j_jds1170_fn_001">†</xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Zhao</surname><given-names>Kangyi</given-names></name><xref ref-type="aff" rid="j_jds1170_aff_002">2</xref><xref ref-type="fn" rid="j_jds1170_fn_001">†</xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Huang</surname><given-names>Penghui</given-names></name><xref ref-type="aff" rid="j_jds1170_aff_001">1</xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Celedón</surname><given-names>Juan C.</given-names></name><xref ref-type="aff" rid="j_jds1170_aff_003">3</xref>
</contrib>
<contrib contrib-type="author">
<name><surname>McKennan</surname><given-names>Chris</given-names></name><xref ref-type="aff" rid="j_jds1170_aff_002">2</xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Chen</surname><given-names>Wei</given-names></name><xref ref-type="aff" rid="j_jds1170_aff_003">3</xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Wang</surname><given-names>Jiebiao</given-names></name><email xlink:href="mailto:jbwang@pitt.edu">jbwang@pitt.edu</email><xref ref-type="aff" rid="j_jds1170_aff_001">1</xref><xref ref-type="corresp" rid="cor2">∗</xref>
</contrib>
<aff id="j_jds1170_aff_001"><label>1</label>Department of Biostatistics and Health Data Science, <institution>University of Pittsburgh</institution>, <country>USA</country></aff>
<aff id="j_jds1170_aff_002"><label>2</label>Department of Statistics, <institution>University of Pittsburgh</institution>, <country>USA</country></aff>
<aff id="j_jds1170_aff_003"><label>3</label>Department of Pediatrics, <institution>University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh</institution>, <country>USA</country></aff>
</contrib-group>
<author-notes>
<fn id="j_jds1170_fn_001"><label>†</label>
<p>These authors contributed equally to this work.</p></fn><corresp id="cor2"><label>∗</label>Corresponding author. Email: <ext-link ext-link-type="uri" xlink:href="mailto:jbwang@pitt.edu">jbwang@pitt.edu</ext-link>.</corresp>
</author-notes>
<pub-date pub-type="ppub"><year>2025</year></pub-date><pub-date pub-type="epub"><day>26</day><month>2</month><year>2025</year></pub-date><volume>23</volume><issue>4</issue><fpage>592</fpage><lpage>606</lpage><supplementary-material id="S1" content-type="archive" xlink:href="jds1170_s001.zip" mimetype="application" mime-subtype="x-zip-compressed">
<caption>
<title>Supplementary Material</title>
<p>R package EMixed is publicly hosted on GitHub (<uri>https://github.com/manqicai/EMixed</uri>)</p>
</caption>
</supplementary-material><history><date date-type="received"><day>1</day><month>10</month><year>2024</year></date><date date-type="accepted"><day>24</day><month>1</month><year>2025</year></date></history>
<permissions><copyright-statement>2025 The Author(s). Published by the School of Statistics and the Center for Applied Statistics, Renmin University of China.</copyright-statement><copyright-year>2025</copyright-year>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
<license-p>Open access article under the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">CC BY</ext-link> license.</license-p></license></permissions>
<abstract>
<p>Cellular deconvolution is a key approach to deciphering the complex cellular makeup of tissues by inferring the composition of cell types from bulk data. Traditionally, deconvolution methods have focused on a single molecular modality, relying either on RNA sequencing (RNA-seq) to capture gene expression or on DNA methylation (DNAm) to reveal epigenetic profiles. While these single-modality approaches have provided important insights, they often lack the depth needed to fully understand the intricacies of cellular compositions, especially in complex tissues. To address these limitations, we introduce EMixed, a versatile framework designed for both single-modality and multi-omics cellular deconvolution. EMixed models raw RNA counts and DNAm counts or frequencies via allocation models that assign RNA transcripts and DNAm reads to cell types, and uses an expectation-maximization (EM) algorithm to estimate parameters. Benchmarking results demonstrate that EMixed significantly outperforms existing methods across both single-modality and multi-modality applications, underscoring the broad utility of this approach in enhancing our understanding of cellular heterogeneity.</p>
</abstract>
<kwd-group>
<label>Keywords</label>
<kwd>cellular deconvolution</kwd>
<kwd>DNA methylation</kwd>
<kwd>EM algorithm</kwd>
<kwd>gene expression</kwd>
<kwd>latent Dirichlet allocation</kwd>
<kwd>multi-omics</kwd>
</kwd-group>
<funding-group><funding-statement>This research was funded in part through NIH’s R01AG080590, R03OD034501, R01HL117191, and R21HL150431.</funding-statement></funding-group>
</article-meta>
</front>
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