diff --git a/_papers/Gu2026SpatiotemporalHeterogeneity.yml b/_papers/Gu2026SpatiotemporalHeterogeneity.yml new file mode 100644 index 0000000..a3bb5e0 --- /dev/null +++ b/_papers/Gu2026SpatiotemporalHeterogeneity.yml @@ -0,0 +1,64 @@ +--- +generated: true +bibkey: Gu2026SpatiotemporalHeterogeneity +title: Spatiotemporal Heterogeneity of HPV Integration Architectures Drive Oncogenic Features of Oropharyngeal + Cancer. +author_list: +- citation_name: Gu W +- citation_name: Bhangale AD +- citation_name: Du X +- citation_name: Deng X +- citation_name: Gensterblum-Miller EU +- citation_name: Currie J +- citation_name: Brummel CV +- citation_name: Nyabashi V +- citation_name: Buchakjian M +- citation_name: Casper KA +- citation_name: Chinn SE +- citation_name: Forner D +- citation_name: Malloy KM +- citation_name: Mierzwa ML +- citation_name: Prince ME +- citation_name: Shah JL +- citation_name: Shuman AG +- citation_name: Stucken CL +- citation_name: Swiecicki PL +- citation_name: Worden FP +- citation_name: Yalamanchi P +- citation_name: McHugh JB +- citation_name: Lang Kuhs KA +- citation_name: Boyle AP + member_url: /people/Alan_Boyle/ + member_name: Alan P. Boyle, Ph.D. +- citation_name: Jiang H +- citation_name: Heft Neal ME +- citation_name: Spector ME +- citation_name: Mills RE +- citation_name: Brenner JC +year: 2026 +sort_date: '2026-10-03' +members: +- xmdu +- apboyle +bibtex: |- + @article{Gu2026SpatiotemporalHeterogeneity, + author = {Gu, Wenjin and Bhangale, Apurva Dhanesh and Du, Xiaomeng and Deng, Xinyi and Gensterblum-Miller, Elizabeth U and Currie, Jordan and Brummel, Collin V and Nyabashi, Vital and Buchakjian, Marisa and Casper, Keith A and Chinn, Steven E and Forner, David and Malloy, Kelly M and Mierzwa, Michelle L and Prince, Mark E and Shah, Jennifer L and Shuman, Andrew G and Stucken, Chaz L and Swiecicki, Paul L and Worden, Francis P and Yalamanchi, Pratyusha and McHugh, Jonathan B and Lang Kuhs, Krystle A and Boyle, Alan P and Jiang, Hui and Heft Neal, Molly E and Spector, Matthew E and Mills, Ryan E and Brenner, J Chad}, + title = {{Spatiotemporal Heterogeneity of HPV Integration Architectures Drive Oncogenic Features of Oropharyngeal Cancer.}}, + journal = {bioRxiv : the preprint server for biology}, + year = {2026}, + month = {10}, + day = {10}, + abstract = {Viral integration is common in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC), but its structural and clinical significance remains unclear. We integrated targeted capture sequencing of 197 HPV+ OPSCCs with long-read nanopore sequencing of 17 tumors and models to characterize HPV-host rearrangements. We developed a novel quantitative informatics framework that classifies integration structures as Type1 (simple, single/low-copy) or Type2 (clustered, high-copy, rearranged). HPV integration occurred in 83\% of tumors, with recurrent hotspots including TP63, MYC, CD274, TRAF2, and KMT2C . Type2 events were enriched for HPV E2 disruption, focal human amplifications, preferential transcription, and noncanonical HPV-host RNA fusion isoforms. Type2 tumors showed increased HPV oncogene expression and activation of MYC, NF-κB/TNFα, PI3K-AKT-mTOR, Hippo/YAP-TAZ, and epithelial stemness programs. Multi-region and longitudinal analyses revealed intratumoral heterogeneity and clonal selection of Type2 architectures during progression, supporting integration structure as a potential marker of aggressive behavior and risk stratification.}, + doi = {10.64898/2026.10.03.756294}, + url = {https://doi.org/10.64898/2026.10.03.756294}, + note = {{PMID:} 42926491} + } +status: preprint +journal: 'bioRxiv : the preprint server for biology' +doi: 10.64898/2026.10.03.756294 +PMID: '42926491' +primary_url: https://doi.org/10.64898/2026.10.03.756294 +biorxiv: https://doi.org/10.64898/2026.10.03.756294 +abstract: |- + Viral integration is common in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC), but its structural and clinical significance remains unclear. We integrated targeted capture sequencing of 197 HPV+ OPSCCs with long-read nanopore sequencing of 17 tumors and models to characterize HPV-host rearrangements. We developed a novel quantitative informatics framework that classifies integration structures as Type1 (simple, single/low-copy) or Type2 (clustered, high-copy, rearranged). HPV integration occurred in 83% of tumors, with recurrent hotspots including TP63, MYC, CD274, TRAF2, and KMT2C . Type2 events were enriched for HPV E2 disruption, focal human amplifications, preferential transcription, and noncanonical HPV-host RNA fusion isoforms. Type2 tumors showed increased HPV oncogene expression and activation of MYC, NF-κB/TNFα, PI3K-AKT-mTOR, Hippo/YAP-TAZ, and epithelial stemness programs. Multi-region and longitudinal analyses revealed intratumoral heterogeneity and clonal selection of Type2 architectures during progression, supporting integration structure as a potential marker of aggressive behavior and risk stratification. +--- diff --git a/assets/ABoyle_CV.pdf b/assets/ABoyle_CV.pdf index 55f770d..bdfb638 100644 Binary files a/assets/ABoyle_CV.pdf and b/assets/ABoyle_CV.pdf differ diff --git a/bibliography/publications.bib b/bibliography/publications.bib index 68cb9a3..f952c86 100644 --- a/bibliography/publications.bib +++ b/bibliography/publications.bib @@ -3,6 +3,19 @@ % Citation keys are permanent ASCII identifiers in FirstAuthorYearMnemonic form. % Once assigned, a key must not change when a preprint is updated or formally published. +@article{Gu2026SpatiotemporalHeterogeneity, + author = {Gu, Wenjin and Bhangale, Apurva Dhanesh and Du, Xiaomeng and Deng, Xinyi and Gensterblum-Miller, Elizabeth U and Currie, Jordan and Brummel, Collin V and Nyabashi, Vital and Buchakjian, Marisa and Casper, Keith A and Chinn, Steven E and Forner, David and Malloy, Kelly M and Mierzwa, Michelle L and Prince, Mark E and Shah, Jennifer L and Shuman, Andrew G and Stucken, Chaz L and Swiecicki, Paul L and Worden, Francis P and Yalamanchi, Pratyusha and McHugh, Jonathan B and Lang Kuhs, Krystle A and Boyle, Alan P and Jiang, Hui and Heft Neal, Molly E and Spector, Matthew E and Mills, Ryan E and Brenner, J Chad}, + title = {{Spatiotemporal Heterogeneity of HPV Integration Architectures Drive Oncogenic Features of Oropharyngeal Cancer.}}, + journal = {bioRxiv : the preprint server for biology}, + year = {2026}, + month = {10}, + day = {10}, + abstract = {Viral integration is common in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC), but its structural and clinical significance remains unclear. We integrated targeted capture sequencing of 197 HPV+ OPSCCs with long-read nanopore sequencing of 17 tumors and models to characterize HPV-host rearrangements. We developed a novel quantitative informatics framework that classifies integration structures as Type1 (simple, single/low-copy) or Type2 (clustered, high-copy, rearranged). HPV integration occurred in 83\% of tumors, with recurrent hotspots including TP63, MYC, CD274, TRAF2, and KMT2C . Type2 events were enriched for HPV E2 disruption, focal human amplifications, preferential transcription, and noncanonical HPV-host RNA fusion isoforms. Type2 tumors showed increased HPV oncogene expression and activation of MYC, NF-κB/TNFα, PI3K-AKT-mTOR, Hippo/YAP-TAZ, and epithelial stemness programs. Multi-region and longitudinal analyses revealed intratumoral heterogeneity and clonal selection of Type2 architectures during progression, supporting integration structure as a potential marker of aggressive behavior and risk stratification.}, + doi = {10.64898/2026.10.03.756294}, + url = {https://doi.org/10.64898/2026.10.03.756294}, + note = {{PMID:} 42926491} +} + @article {Deng2026HPVReview, author = {Deng, Xinyi and Du, Xiaomeng and Gensterblum-Miller, Elizabeth and Currie, Jordan and Majchrowski, Behirda Karaj and Lialios, Penelope and Bhangale, Apurva and Spector, Matthew E. and Boyle, Alan P. and {\dag}Brenner, J. Chad and {\dag}Mills, Ryan E.}, title = {Challenges in the detection and assembly of virus integration structures in human genomes}, diff --git a/cv/generated/patents.tex b/cv/generated/patents.tex index 94bc3db..efd397a 100644 --- a/cv/generated/patents.tex +++ b/cv/generated/patents.tex @@ -1,6 +1,18 @@ % Generated by scripts/build_cv.py. Do not edit directly. % Source: cv/patents.bib. \cvsection{Patents} -\begin{enumerate}[leftmargin=2.7em,labelsep=0.55em,itemsep=0.65em,parsep=0pt,topsep=0.25em] +\begin{list}{}{% + \usecounter{enumi}% + \setlength{\leftmargin}{2.7em}% + \setlength{\rightmargin}{0pt}% + \setlength{\labelsep}{0.55em}% + \setlength{\labelwidth}{\dimexpr\leftmargin-\labelsep\relax}% + \setlength{\itemindent}{0pt}% + \setlength{\listparindent}{0pt}% + \setlength{\itemsep}{0.65em}% + \setlength{\parsep}{0pt}% + \setlength{\topsep}{0.25em}% + \setlength{\partopsep}{0pt}% +} \item[{[1]}] Karczewski K, Snyder M, Butte AJ, Dudley JT, Hong E, \textbf{Boyle A}, Cherry MJ, Park J. ``Method and System for the Use of Biomarkers for Regulatory Dysfunction in Disease.'' Granted United States patent 9,946,835, 2018. \href{\detokenize{https://patents.google.com/patent/US9946835B2/en}}{Patent record}. -\end{enumerate} +\end{list} diff --git a/cv/generated/publications.tex b/cv/generated/publications.tex index dee731c..3fa5077 100644 --- a/cv/generated/publications.tex +++ b/cv/generated/publications.tex @@ -4,8 +4,21 @@ \begin{flushright} \scriptsize * co-first authorship; \(\dagger\) co-senior authorship; \underline{underline} indicates Boyle Lab members \end{flushright} -\begin{enumerate}[leftmargin=2.7em,labelsep=0.55em,itemsep=0.65em,parsep=0pt,topsep=0.25em] -\item[{[89]}] The Somatic Mosaicism across Human Tissues Network (SMaHT). ``Comprehensive benchmarking of somatic mutation detection by the SMaHT Network.'' \textit{Cell} 2026, 189:6594--6612.e21. \href{\detokenize{https://pubmed.ncbi.nlm.nih.gov/42880231/}}{PMID: 42880231}. +\begin{list}{}{% + \usecounter{enumi}% + \setlength{\leftmargin}{2.7em}% + \setlength{\rightmargin}{0pt}% + \setlength{\labelsep}{0.55em}% + \setlength{\labelwidth}{\dimexpr\leftmargin-\labelsep\relax}% + \setlength{\itemindent}{0pt}% + \setlength{\listparindent}{0pt}% + \setlength{\itemsep}{0.65em}% + \setlength{\parsep}{0pt}% + \setlength{\topsep}{0.25em}% + \setlength{\partopsep}{0pt}% +} +\item[{[90]}] The Somatic Mosaicism across Human Tissues Network (SMaHT). ``Comprehensive benchmarking of somatic mutation detection by the SMaHT Network.'' \textit{Cell} 2026, 189:6594--6612.e21. \href{\detokenize{https://pubmed.ncbi.nlm.nih.gov/42880231/}}{PMID: 42880231}. +\item[{[89]}] Gu W, Bhangale AD, \underline{Du X}, Deng X, Gensterblum-Miller EU, Currie J, Brummel CV, Nyabashi V, Buchakjian M, Casper KA, Chinn SE, Forner D, Malloy KM, Mierzwa ML, Prince ME, Shah JL, Shuman AG, Stucken CL, Swiecicki PL, Worden FP, Yalamanchi P, McHugh JB, Lang Kuhs KA, \textbf{Boyle AP}, Jiang H, Heft Neal ME, Spector ME, Mills RE, Brenner JC. ``Spatiotemporal Heterogeneity of HPV Integration Architectures Drive Oncogenic Features of Oropharyngeal Cancer.'' \textit{bioRxiv : the preprint server for biology} 2026. \href{\detokenize{https://pubmed.ncbi.nlm.nih.gov/42926491/}}{PMID: 42926491}. \item[{[88]}] Denstaedt SJ, \underline{McBean B}, \textbf{Boyle AP}, Arenberg BC, Mack M, Moore BB, Newstead MW, Deng Y, Nesvizhskii AI, Singer BH, Cano J, Prescott HC, Goodridge HS, Zemans RL. ``Long-term immune reprogramming of classical monocytes with altered ontogeny mediates enhanced lung injury in sepsis survivors.'' \textit{JCI Insight} 2026. \href{\detokenize{https://pubmed.ncbi.nlm.nih.gov/40475424/}}{PMID: 40475424}. \item[{[87]}] Deng X, Du X, Gensterblum-Miller E, Currie J, Majchrowski BK, Lialios P, Bhangale A, Spector ME, \textbf{Boyle AP}, \textsuperscript{\(\dagger\)}Brenner JC, \textsuperscript{\(\dagger\)}Mills RE. ``Challenges in the detection and assembly of virus integration structures in human genomes.'' \textit{Frontiers in Oncology} 2026, 16:1925720. \href{\detokenize{https://pubmed.ncbi.nlm.nih.gov/42807781/}}{PMID: 42807781}. \item[{[86]}] The Somatic Mosaicism across Human Tissues Network. ``Integrated map of somatic mosaicism across human tissues in 25 individuals.'' \textit{bioRxiv} 2026. \href{\detokenize{https://doi.org/10.64898/2026.09.01.748636}}{doi: 10.64898/2026.09.01.748636}. @@ -94,4 +107,4 @@ \item[{[3]}] \textbf{Boyle AP}, Bridges S. ``Clustering of archael gene regulatory regions.'' \textit{FASEB Journal} 2003, 17(5):A985. \item[{[2]}] \textbf{Boyle AP}, Boyle JA. ``Visualization of aligned genomic open reading frame data.'' \textit{Biochemistry and Molecular Biology Education} 2003, 31(1):64--68. \href{\detokenize{https://doi.org/10.1002/bmb.2003.494031010144}}{doi: 10.1002/bmb.2003.494031010144}. \item[{[1]}] Wan X, Bridges SM, Boyle JA, \textbf{Boyle AP}. ``Interactive clustering for exploration of genomic data.'' \textit{Proceedings of the Artificial Neural Networks in Engineering Conference} 2002, 12:753--758. \href{\detokenize{https://boylelab.org/pubs/ANNIE_2002_Wan.pdf}}{Publication link}. -\end{enumerate} +\end{list} diff --git a/pub.bib b/pub.bib index d71cb49..0aa64a9 100644 --- a/pub.bib +++ b/pub.bib @@ -3,6 +3,19 @@ % Edit the source file(s) in bibliography/, not this combined file. % Citation keys are permanent ASCII FirstAuthorYearMnemonic identifiers. +@article{Gu2026SpatiotemporalHeterogeneity, + author = {Gu, Wenjin and Bhangale, Apurva Dhanesh and Du, Xiaomeng and Deng, Xinyi and Gensterblum-Miller, Elizabeth U and Currie, Jordan and Brummel, Collin V and Nyabashi, Vital and Buchakjian, Marisa and Casper, Keith A and Chinn, Steven E and Forner, David and Malloy, Kelly M and Mierzwa, Michelle L and Prince, Mark E and Shah, Jennifer L and Shuman, Andrew G and Stucken, Chaz L and Swiecicki, Paul L and Worden, Francis P and Yalamanchi, Pratyusha and McHugh, Jonathan B and Lang Kuhs, Krystle A and Boyle, Alan P and Jiang, Hui and Heft Neal, Molly E and Spector, Matthew E and Mills, Ryan E and Brenner, J Chad}, + title = {{Spatiotemporal Heterogeneity of HPV Integration Architectures Drive Oncogenic Features of Oropharyngeal Cancer.}}, + journal = {bioRxiv : the preprint server for biology}, + year = {2026}, + month = {10}, + day = {10}, + abstract = {Viral integration is common in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC), but its structural and clinical significance remains unclear. We integrated targeted capture sequencing of 197 HPV+ OPSCCs with long-read nanopore sequencing of 17 tumors and models to characterize HPV-host rearrangements. We developed a novel quantitative informatics framework that classifies integration structures as Type1 (simple, single/low-copy) or Type2 (clustered, high-copy, rearranged). HPV integration occurred in 83\% of tumors, with recurrent hotspots including TP63, MYC, CD274, TRAF2, and KMT2C . Type2 events were enriched for HPV E2 disruption, focal human amplifications, preferential transcription, and noncanonical HPV-host RNA fusion isoforms. Type2 tumors showed increased HPV oncogene expression and activation of MYC, NF-κB/TNFα, PI3K-AKT-mTOR, Hippo/YAP-TAZ, and epithelial stemness programs. Multi-region and longitudinal analyses revealed intratumoral heterogeneity and clonal selection of Type2 architectures during progression, supporting integration structure as a potential marker of aggressive behavior and risk stratification.}, + doi = {10.64898/2026.10.03.756294}, + url = {https://doi.org/10.64898/2026.10.03.756294}, + note = {{PMID:} 42926491} +} + @article {Deng2026HPVReview, author = {Deng, Xinyi and Du, Xiaomeng and Gensterblum-Miller, Elizabeth and Currie, Jordan and Majchrowski, Behirda Karaj and Lialios, Penelope and Bhangale, Apurva and Spector, Matthew E. and Boyle, Alan P. and {\dag}Brenner, J. Chad and {\dag}Mills, Ryan E.}, title = {Challenges in the detection and assembly of virus integration structures in human genomes}, diff --git a/publication_metadata/gu2026spatiotemporalheterogeneity.yml b/publication_metadata/gu2026spatiotemporalheterogeneity.yml new file mode 100644 index 0000000..9b1a2c1 --- /dev/null +++ b/publication_metadata/gu2026spatiotemporalheterogeneity.yml @@ -0,0 +1,3 @@ +bibkey: Gu2026SpatiotemporalHeterogeneity +members: +- apboyle