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1. Discovery of several thousand highly diverse circular DNA viruses

Author

Tisza, Michael J, Pastrana, Diana V, Welch, Nicole L, Stewart, Brittany, Peretti, Alberto, Starrett, Gabriel J, Pang, Yuk-Ying S, Krishnamurthy, Siddharth R, Pesavento, Patricia A, McDermott, David H, Murphy, Philip M, Whited, Jessica L, Miller, Bess, Brenchley, Jason, Rosshart, Stephan P, Rehermann, Barbara, Doorbar, John, Ta'ala, Blake A, Pletnikova, Olga, Troncoso, Juan C, Resnick, Susan M, Bolduc, Ben, Sullivan, Matthew B, Varsani, Arvind, Segall, Anca M, and Buck, Christopher B

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Infectious Diseases, Biotechnology, Aetiology, 2.2 Factors relating to the physical environment, Infection, Animals, Capsid Proteins, DNA Virus Infections, DNA Viruses, DNA, Circular, DNA, Viral, Genome, Viral, Humans, Molecular Sequence Annotation, Software, evolutionary biology, infectious disease, metagenomics, microbiology, microbiome, viral evolution, virus, Biochemistry and Cell Biology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Although millions of distinct virus species likely exist, only approximately 9000 are catalogued in GenBank's RefSeq database. We selectively enriched for the genomes of circular DNA viruses in over 70 animal samples, ranging from nematodes to human tissue specimens. A bioinformatics pipeline, Cenote-Taker, was developed to automatically annotate over 2500 complete genomes in a GenBank-compliant format. The new genomes belong to dozens of established and emerging viral families. Some appear to be the result of previously undescribed recombination events between ssDNA and ssRNA viruses. In addition, hundreds of circular DNA elements that do not encode any discernable similarities to previously characterized sequences were identified. To characterize these 'dark matter' sequences, we used an artificial neural network to identify candidate viral capsid proteins, several of which formed virus-like particles when expressed in culture. These data further the understanding of viral sequence diversity and allow for high throughput documentation of the virosphere.

Published
2020

3. ViroPanel: Hybrid Capture and Massively Parallel Sequencing for Simultaneous Detection and Profiling of Oncogenic Virus Infection and Tumor Genome

Author

Slevin, Michael K., Wollison, Bruce M., Powers, Winslow, Burns, Robert T., Patel, Neil, Ducar, Matthew D., Starrett, Gabriel J., Garcia, Elizabeth P., Manning, Danielle K., Cheng, Jingwei, Hanna, Glenn J., Kaye, Kenneth M., Van Hummelen, Paul, Nag, Anwesha, Thorner, Aaron R., DeCaprio, James A., and MacConaill, Laura E.

Published
2020
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6. Microhomology‐mediated repair machinery and its relationship with HPV‐mediated oncogenesis.

Author

Chatterjee, Subhajit and Starrett, Gabriel J.

Subjects
DOUBLE-strand DNA breaks, HUMAN papillomavirus, DNA viruses, CARCINOGENESIS
Abstract

Human Papillomaviruses (HPV) are a diverse family of non‐enveloped dsDNA viruses that infect the skin and mucosal epithelia. Persistent HPV infections can lead to cancer frequently involving integration of the virus into the host genome, leading to sustained oncogene expression and loss of capsid and genome maintenance proteins. Microhomology‐mediated double‐strand break repair, a DNA double‐stranded breaks repair pathway present in many organisms, was initially thought to be a backup but it's now seen as vital, especially in homologous recombination‐deficient contexts. Increasing evidence has identified microhomology (MH) near HPV integration junctions, suggesting MH‐mediated repair pathways drive integration. In this comprehensive review, we present a detailed summary of both the mechanisms underlying MH‐mediated repair and the evidence for its involvement in HPV integration in cancer. Lastly, we highlight the involvement of these processes in the integration of other DNA viruses and the broader implications on virus lifecycles and host innate immune response. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Table S1 from Analysis of Several Common APOBEC-type Mutations in Bladder Tumors Suggests Links to Viral Infection

Author

Rao, Nina, primary, Starrett, Gabriel J., primary, Piaskowski, Mary L., primary, Butler, Kelly E., primary, Golubeva, Yelena, primary, Yan, Wusheng, primary, Lawrence, Scott M., primary, Dean, Michael, primary, Garcia-Closas, Montserrat, primary, Baris, Dalsu, primary, Johnson, Alison, primary, Schwenn, Molly, primary, Malats, Nuria, primary, Real, Francisco X., primary, Kogevinas, Manolis, primary, Rothman, Nathaniel, primary, Silverman, Debra T., primary, Dyrskjøt, Lars, primary, Buck, Christopher B., primary, Koutros, Stella, primary, and Prokunina-Olsson, Ludmila, primary

Published
2023
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8. Data from Analysis of Several Common APOBEC-type Mutations in Bladder Tumors Suggests Links to Viral Infection

Author

Rao, Nina, primary, Starrett, Gabriel J., primary, Piaskowski, Mary L., primary, Butler, Kelly E., primary, Golubeva, Yelena, primary, Yan, Wusheng, primary, Lawrence, Scott M., primary, Dean, Michael, primary, Garcia-Closas, Montserrat, primary, Baris, Dalsu, primary, Johnson, Alison, primary, Schwenn, Molly, primary, Malats, Nuria, primary, Real, Francisco X., primary, Kogevinas, Manolis, primary, Rothman, Nathaniel, primary, Silverman, Debra T., primary, Dyrskjøt, Lars, primary, Buck, Christopher B., primary, Koutros, Stella, primary, and Prokunina-Olsson, Ludmila, primary

Published
2023
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9. Figure S1 from Analysis of Several Common APOBEC-type Mutations in Bladder Tumors Suggests Links to Viral Infection

Author

Rao, Nina, primary, Starrett, Gabriel J., primary, Piaskowski, Mary L., primary, Butler, Kelly E., primary, Golubeva, Yelena, primary, Yan, Wusheng, primary, Lawrence, Scott M., primary, Dean, Michael, primary, Garcia-Closas, Montserrat, primary, Baris, Dalsu, primary, Johnson, Alison, primary, Schwenn, Molly, primary, Malats, Nuria, primary, Real, Francisco X., primary, Kogevinas, Manolis, primary, Rothman, Nathaniel, primary, Silverman, Debra T., primary, Dyrskjøt, Lars, primary, Buck, Christopher B., primary, Koutros, Stella, primary, and Prokunina-Olsson, Ludmila, primary

Published
2023
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10. Analysis of Several Common APOBEC-type Mutations in Bladder Tumors Suggests Links to Viral Infection

Author

Rao, Nina, primary, Starrett, Gabriel J., additional, Piaskowski, Mary L., additional, Butler, Kelly E., additional, Golubeva, Yelena, additional, Yan, Wusheng, additional, Lawrence, Scott M., additional, Dean, Michael, additional, Garcia-Closas, Montserrat, additional, Baris, Dalsu, additional, Johnson, Alison, additional, Schwenn, Molly, additional, Malats, Nuria, additional, Real, Francisco X., additional, Kogevinas, Manolis, additional, Rothman, Nathaniel, additional, Silverman, Debra T., additional, Dyrskjøt, Lars, additional, Buck, Christopher B., additional, Koutros, Stella, additional, and Prokunina-Olsson, Ludmila, additional

Published
2023
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14. The Virome of Bladder Tumors Arising in People Living With HIV.

Author

Starrett, Gabriel J., Foster, Haidn, Sigel, Keith, Yuxin Liu, and Engels, Eric A.

Abstract

Background: People living with HIV (PLWH) have elevated risk for developing virus-related cancers. Bladder cancer risk is not increased in PLWH but is elevated among immunosuppressed solid organ transplant recipients (SOTRs). BK polyomavirus and, to a lesser extent, other viruses have been detected in bladder cancers from SOTRs. Objective: To characterize the virome of bladder tumors in PLWH. Design: Retrospective case series. Methods: We sequenced DNA and RNA from archived formalin- fixed bladder tumors from PLWH. Nonhuman reads were assembled and matched to a database of known viruses. Results: Fifteen bladder tumors from PLWH (13 carcinomas, 2 benign tumors) were evaluated. Fourteen tumors were in men, and the median age at diagnosis was 59 years (median CD4 count 460 cells/mm3). All but 1 tumor yielded both sufficient DNA and RNA. One bladder cancer, arising in a 52-year-old man with a CD4 count of 271 cells/mm³, manifested diverse Alphatorquevirus DNA and RNA sequences. A second cancer arising in a 58-year-old male former smoker (CD4 count of 227 cells/mm³) also showed Alphatorquevirus and Gammatorquevirus DNA sequences. Neither tumor exhibited viral integration. Conclusions: Alphatorqueviruses and Gammatorqueviruses are anelloviruses, which have also been detected in bladder cancers from SOTRs, but anelloviruses are common infections, and detection may simply reflect increased abundance in the setting of immunosuppression. The lack of detection of BK polyomavirus among bladder tumors from PLWH parallels the lower level of bladder cancer risk seen in PLWH compared with SOTRs, indirectly supporting a role for BK polyomavirus in causing the excess risk in SOTRs. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Mutational impact of APOBEC3A and APOBEC3B in a human cell line and comparisons to breast cancer.

Author

Carpenter, Michael A., Temiz, Nuri A., Ibrahim, Mahmoud A., Jarvis, Matthew C., Brown, Margaret R., Argyris, Prokopios P., Brown, William L., Starrett, Gabriel J., Yee, Douglas, and Harris, Reuben S.

Subjects
BREAST, GENE expression, CELL lines, DELETION mutation, WHOLE genome sequencing, BREAST cancer, ADENINE, CYTOSINE
Abstract

A prominent source of mutation in cancer is single-stranded DNA cytosine deamination by cellular APOBEC3 enzymes, which results in signature C-to-T and C-to-G mutations in TCA and TCT motifs. Although multiple enzymes have been implicated, reports conflict and it is unclear which protein(s) are responsible. Here we report the development of a selectable system to quantify genome mutation and demonstrate its utility by comparing the mutagenic activities of three leading candidates—APOBEC3A, APOBEC3B, and APOBEC3H. The human cell line, HAP1, is engineered to express the thymidine kinase (TK) gene of HSV-1, which confers sensitivity to ganciclovir. Expression of APOBEC3A and APOBEC3B, but not catalytic mutant controls or APOBEC3H, triggers increased frequencies of TK mutation and similar TC-biased cytosine mutation profiles in the selectable TK reporter gene. Whole genome sequences from independent clones enabled an analysis of thousands of single base substitution mutations and extraction of local sequence preferences with APOBEC3A preferring YTCW motifs 70% of the time and APOBEC3B 50% of the time (Y = C/T; W = A/T). Signature comparisons with breast tumor whole genome sequences indicate that most malignancies manifest intermediate percentages of APOBEC3 signature mutations in YTCW motifs, mostly between 50 and 70%, suggesting that both enzymes contribute in a combinatorial manner to the overall mutation landscape. Although the vast majority of APOBEC3A- and APOBEC3B-induced single base substitution mutations occur outside of predicted chromosomal DNA hairpin structures, whole genome sequence analyses and supporting biochemical studies also indicate that both enzymes are capable of deaminating the single-stranded loop regions of DNA hairpins at elevated rates. These studies combine to help resolve a long-standing etiologic debate on the source of APOBEC3 signature mutations in cancer and indicate that future diagnostic and therapeutic efforts should focus on both APOBEC3A and APOBEC3B. Author summary: A large source of mutation in cancer is attributable to single-stranded DNA cytosine to uracil (C-to-U) deamination by APOBEC3 family enzymes. Chromosomal DNA U's directly template the insertion of adenine (A), which results in C/G-to-T/A mutations. Chromosomal U's also trigger error-prone DNA repair processes, which less directly result in C/G-to-T/A mutations, C/G-to-G/C mutations, and more complex events such as insertion/deletion mutations. We report a human cell line for cancer mutation studies, where mutations can be identified selectively or by genomic DNA sequencing. Only APOBEC3A and APOBEC3B proved capable of inflicting the aforementioned types of single base substitution mutations. Interestingly, 70% and 50% of the single base substitution mutations attributable to APOBEC3A and APOBEC3B, respectively, occurred in TCA and TCT trinucleotide motifs preceded by a pyrimidine (T or C). This is significant because most APOBEC3-positive breast tumors exhibit an intermediate percentage of signature mutations in these broader tetranucleotide motifs, which supports the idea that both APOBEC3A and APOBEC3B contribute in a combinatorial manner to the overall mutation landscape in these tumors. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Tables S1-S3 and Figures S1-S2 from APOBEC3G Expression Correlates with T-Cell Infiltration and Improved Clinical Outcomes in High-grade Serous Ovarian Carcinoma

Author

Leonard, Brandon, primary, Starrett, Gabriel J., primary, Maurer, Matthew J., primary, Oberg, Ann L., primary, Van Bockstal, Mieke, primary, Van Dorpe, Jo, primary, De Wever, Olivier, primary, Helleman, Jozien, primary, Sieuwerts, Anieta M., primary, Berns, Els M.J.J., primary, Martens, John W.M., primary, Anderson, Brett D., primary, Brown, William L., primary, Kalli, Kimberly R., primary, Kaufmann, Scott H., primary, and Harris, Reuben S., primary

Published
2023
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18. Supplementary Figures S1 through S6 and Supplementary Tables S1 and S2 from The PKC/NF-κB Signaling Pathway Induces APOBEC3B Expression in Multiple Human Cancers

Author

Leonard, Brandon, primary, McCann, Jennifer L., primary, Starrett, Gabriel J., primary, Kosyakovsky, Leah, primary, Luengas, Elizabeth M., primary, Molan, Amy M., primary, Burns, Michael B., primary, McDougle, Rebecca M., primary, Parker, Peter J., primary, Brown, William L., primary, and Harris, Reuben S., primary

Published
2023
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19. Evidence for virus-mediated oncogenesis in bladder cancers arising in solid organ transplant recipients

Author

Starrett, Gabriel J, primary, Yu, Kelly, additional, Golubeva, Yelena, additional, Lenz, Petra, additional, Piaskowski, Mary L, additional, Petersen, David, additional, Dean, Michael, additional, Israni, Ajay, additional, Hernandez, Brenda Y, additional, Tucker, Thomas C, additional, Cheng, Iona, additional, Gonsalves, Lou, additional, Morris, Cyllene R, additional, Hussain, Shehnaz K, additional, Lynch, Charles F, additional, Harris, Reuben S, additional, Prokunina-Olsson, Ludmila, additional, Meltzer, Paul S, additional, Buck, Christopher B, additional, and Engels, Eric A, additional

Published
2023
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20. Author response: Evidence for virus-mediated oncogenesis in bladder cancers arising in solid organ transplant recipients

Author

Starrett, Gabriel J, primary, Yu, Kelly, additional, Golubeva, Yelena, additional, Lenz, Petra, additional, Piaskowski, Mary L, additional, Petersen, David, additional, Dean, Michael, additional, Israni, Ajay, additional, Hernandez, Brenda Y, additional, Tucker, Thomas C, additional, Cheng, Iona, additional, Gonsalves, Lou, additional, Morris, Cyllene R, additional, Hussain, Shehnaz K, additional, Lynch, Charles F, additional, Harris, Reuben S, additional, Prokunina-Olsson, Ludmila, additional, Meltzer, Paul S, additional, Buck, Christopher B, additional, and Engels, Eric A, additional

Published
2023
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24. Virally mediated mechanisms of HLA class I loss in Merkel cell carcinoma and implications for viral epitope presentation

Author

Keskin, Derin B., primary, Lee, Patrick C., additional, Klaeger, Susan, additional, Le, Phuong M., additional, Korthauer, Keegan, additional, Cheng, Jingwei, additional, Ananthapadmanabhan, Varsha, additional, Frost, Thomas C., additional, Iorgulescu, J. Bryan, additional, Lemvigh, Camilla K., additional, Pedersen, Christina B., additional, Sarkizova, Siranush, additional, Li, Shuqiang, additional, Liu, Xiaoxi, additional, Doherty, Laura M., additional, Neuberg, Donna, additional, Zhang, Guanglan, additional, Olsen, Lars R., additional, Thakuria, Manisha, additional, Rodig, Scott J., additional, Clauser, Karl R., additional, Starrett, Gabriel J., additional, Doench, John G., additional, Buhrlage, Sara J., additional, Carr, Steven A., additional, DeCaprio, James A., additional, and Wu, Catherine J., additional

Published
2022
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26. Reversal of viral and epigenetic HLA class I repression in Merkel cell carcinoma

Author

Lee, Patrick C., primary, Klaeger, Susan, additional, Le, Phuong M., additional, Korthauer, Keegan, additional, Cheng, Jingwei, additional, Ananthapadmanabhan, Varsha, additional, Frost, Thomas C., additional, Stevens, Jonathan D., additional, Wong, Alan Y.L., additional, Iorgulescu, J. Bryan, additional, Tarren, Anna Y., additional, Chea, Vipheaviny A., additional, Carulli, Isabel P., additional, Lemvigh, Camilla K., additional, Pedersen, Christina B., additional, Gartin, Ashley K., additional, Sarkizova, Siranush, additional, Wright, Kyle T., additional, Li, Letitia W., additional, Nomburg, Jason, additional, Li, Shuqiang, additional, Huang, Teddy, additional, Liu, Xiaoxi, additional, Pomerance, Lucas, additional, Doherty, Laura M., additional, Apffel, Annie M., additional, Wallace, Luke J., additional, Rachimi, Suzanna, additional, Felt, Kristen D., additional, Wolff, Jacquelyn O., additional, Witten, Elizabeth, additional, Zhang, Wandi, additional, Neuberg, Donna, additional, Lane, William J., additional, Zhang, Guanglan, additional, Olsen, Lars R., additional, Thakuria, Manisha, additional, Rodig, Scott J., additional, Clauser, Karl R., additional, Starrett, Gabriel J., additional, Doench, John G., additional, Buhrlage, Sara J., additional, Carr, Steven A., additional, DeCaprio, James A., additional, Wu, Catherine J., additional, and Keskin, Derin B., additional

Published
2022
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27. Reversal of viral and epigenetic HLA class I repression in Merkel cell carcinoma

Author

Lee, Patrick C., Klaeger, Susan, Le, Phuong M., Korthauer, Keegan, Cheng, Jingwei, Ananthapadmanabhan, Varsha, Frost, Thomas C., Stevens, Jonathan D., Wong, Alan Y.L., Iorgulescu, J. Bryan, Tarren, Anna Y., Chea, Vipheaviny A., Carulli, Isabel P., Lemvigh, Camilla K., Pedersen, Christina B., Gartin, Ashley K., Sarkizova, Siranush, Wright, Kyle T., Li, Letitia W., Nomburg, Jason, Li, Shuqiang, Huang, Teddy, Liu, Xiaoxi, Pomerance, Lucas, Doherty, Laura M., Apffel, Annie M., Wallace, Luke J., Rachimi, Suzanna, Felt, Kristen D., Wolff, Jacquelyn O., Witten, Elizabeth, Zhang, Wandi, Neuberg, Donna, Lane, William J., Zhang, Guanglan, Olsen, Lars R., Thakuria, Manisha, Rodig, Scott J., Clauser, Karl R., Starrett, Gabriel J., Doench, John G., Buhrlage, Sara J., Carr, Steven A., DeCaprio, James A., Wu, Catherine J., Keskin, Derin B., Lee, Patrick C., Klaeger, Susan, Le, Phuong M., Korthauer, Keegan, Cheng, Jingwei, Ananthapadmanabhan, Varsha, Frost, Thomas C., Stevens, Jonathan D., Wong, Alan Y.L., Iorgulescu, J. Bryan, Tarren, Anna Y., Chea, Vipheaviny A., Carulli, Isabel P., Lemvigh, Camilla K., Pedersen, Christina B., Gartin, Ashley K., Sarkizova, Siranush, Wright, Kyle T., Li, Letitia W., Nomburg, Jason, Li, Shuqiang, Huang, Teddy, Liu, Xiaoxi, Pomerance, Lucas, Doherty, Laura M., Apffel, Annie M., Wallace, Luke J., Rachimi, Suzanna, Felt, Kristen D., Wolff, Jacquelyn O., Witten, Elizabeth, Zhang, Wandi, Neuberg, Donna, Lane, William J., Zhang, Guanglan, Olsen, Lars R., Thakuria, Manisha, Rodig, Scott J., Clauser, Karl R., Starrett, Gabriel J., Doench, John G., Buhrlage, Sara J., Carr, Steven A., DeCaprio, James A., Wu, Catherine J., and Keskin, Derin B.

Abstract

Cancers avoid immune surveillance through an array of mechanisms, including perturbation of HLA class I antigen presentation. Merkel cell carcinoma (MCC) is an aggressive, HLA-I–low, neuroendocrine carcinoma of the skin often caused by the Merkel cell polyomavirus (MCPyV). Through the characterization of 11 newly generated MCC patient-derived cell lines, we identified transcriptional suppression of several class I antigen presentation genes. To systematically identify regulators of HLA-I loss in MCC, we performed parallel, genome-scale, gain- and loss-of-function screens in a patient-derived MCPyV-positive cell line and identified MYCL and the non-canonical Polycomb repressive complex 1.1 (PRC1.1) as HLA-I repressors. We observed physical interaction of MYCL with the MCPyV small T viral antigen, supporting a mechanism of virally mediated HLA-I suppression. We further identify the PRC1.1 component USP7 as a pharmacologic target to restore HLA-I expression in MCC.

Published
2022

29. The Transcriptome Architecture of Polyomaviruses

Author

Nomburg, Jason, primary, Zou, Wei, additional, Frost, Thomas C, additional, Datta, Chandreyee, additional, Vasudevan, Shobha, additional, Starrett, Gabriel J, additional, Imperiale, Michael J, additional, Meyerson, Matthew, additional, and DeCaprio, James A, additional

Published
2021
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30. Evidence for Virus-Mediated Oncogenesis in Bladder Cancers Arising in Solid Organ Transplant Recipients

Author

Starrett, Gabriel J, primary, Yu, Kelly, additional, Golubeva, Yelena, additional, Lenz, Petra, additional, Piaskowski, Mary L, additional, Petersen, David, additional, Dean, Michael, additional, Israni, Ajay, additional, Hernandez, Brenda Y, additional, Tucker, Thomas C, additional, Cheng, Iona, additional, Gonsalves, Lou, additional, Morris, Cyllene R, additional, Hussain, Shehnaz K, additional, Lynch, Charles F, additional, Harris, Reuben S, additional, Prokunina-Olsson, Ludmila, additional, Meltzer, Paul, additional, Buck, Christopher B, additional, and Engels, Eric A, additional

Published
2021
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32. Treatment of Relapsing HPV Diseases by Restored Function of Natural Killer Cells

Author

Lisco, Andrea, primary, Hsu, Amy P., additional, Dimitrova, Dimana, additional, Proctor, Diana M., additional, Mace, Emily M., additional, Ye, Peiying, additional, Anderson, Megan V., additional, Hicks, Stephanie N., additional, Grivas, Christopher, additional, Hammoud, Dima A., additional, Manion, Maura, additional, Starrett, Gabriel J., additional, Farrel, Alvin, additional, Dobbs, Kerry, additional, Brownell, Isaac, additional, Buck, Christopher, additional, Notarangelo, Luigi D., additional, Orange, Jordan S., additional, Leonard, Warren J., additional, Orestes, Michael I., additional, Peters, Anju T., additional, Kanakry, Jennifer A., additional, Segre, Julia A., additional, Kong, Heidi H., additional, and Sereti, Irini, additional

Published
2021
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33. Mash Screen: high-throughput sequence containment estimation for genome discovery

Author

Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Ondov, Brian D., Starrett, Gabriel J., Sappington, Anna, Kostic, Aleksandra, Koren, Sergey, Buck, Christopher B., Phillippy, Adam M., Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Ondov, Brian D., Starrett, Gabriel J., Sappington, Anna, Kostic, Aleksandra, Koren, Sergey, Buck, Christopher B., and Phillippy, Adam M.

Abstract

The MinHash algorithm has proven effective for rapidly estimating the resemblance of two genomes or metagenomes. However, this method cannot reliably estimate the containment of a genome within a metagenome. Here, we describe an online algorithm capable of measuring the containment of genomes and proteomes within either assembled or unassembled sequencing read sets. We describe several use cases, including contamination screening and retrospective analysis of metagenomes for novel genome discovery. Using this tool, we provide containment estimates for every NCBI RefSeq genome within every SRA metagenome and demonstrate the identification of a novel polyomavirus species from a public metagenome.

Published
2020

37. APOBEC3A catalyzes mutation and drives carcinogenesis in vivo

Author

Law, Emily K., primary, Levin-Klein, Rena, additional, Jarvis, Matthew C., additional, Kim, Hyoung, additional, Argyris, Prokopios P., additional, Carpenter, Michael A., additional, Starrett, Gabriel J., additional, Temiz, Nuri A., additional, Larson, Lindsay K., additional, Durfee, Cameron, additional, Burns, Michael B., additional, Vogel, Rachel I., additional, Stavrou, Spyridon, additional, Aguilera, Alexya N., additional, Wagner, Sandra, additional, Largaespada, David A., additional, Starr, Timothy K., additional, Ross, Susan R., additional, and Harris, Reuben S., additional

Published
2020
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39. ViroPanel

Author

Slevin, Michael K., primary, Wollison, Bruce M., additional, Powers, Winslow, additional, Burns, Robert T., additional, Patel, Neil, additional, Ducar, Matthew D., additional, Starrett, Gabriel J., additional, Garcia, Elizabeth P., additional, Manning, Danielle K., additional, Cheng, Jingwei, additional, Hanna, Glenn J., additional, Kaye, Kenneth M., additional, Van Hummelen, Paul, additional, Nag, Anwesha, additional, Thorner, Aaron R., additional, DeCaprio, James A., additional, and MacConaill, Laura E., additional

Published
2020
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40. Discovery of several thousand highly diverse circular DNA viruses

Author

Tisza, Michael J, primary, Pastrana, Diana V, additional, Welch, Nicole L, additional, Stewart, Brittany, additional, Peretti, Alberto, additional, Starrett, Gabriel J, additional, Pang, Yuk-Ying S, additional, Krishnamurthy, Siddharth R, additional, Pesavento, Patricia A, additional, McDermott, David H, additional, Murphy, Philip M, additional, Whited, Jessica L, additional, Miller, Bess, additional, Brenchley, Jason, additional, Rosshart, Stephan P, additional, Rehermann, Barbara, additional, Doorbar, John, additional, Ta'ala, Blake A, additional, Pletnikova, Olga, additional, Troncoso, Juan C, additional, Resnick, Susan M, additional, Bolduc, Ben, additional, Sullivan, Matthew B, additional, Varsani, Arvind, additional, Segall, Anca M, additional, and Buck, Christopher B, additional

Published
2020
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41. Author response: Discovery of several thousand highly diverse circular DNA viruses

Author

Tisza, Michael J, primary, Pastrana, Diana V, additional, Welch, Nicole L, additional, Stewart, Brittany, additional, Peretti, Alberto, additional, Starrett, Gabriel J, additional, Pang, Yuk-Ying S, additional, Krishnamurthy, Siddharth R, additional, Pesavento, Patricia A, additional, McDermott, David H, additional, Murphy, Philip M, additional, Whited, Jessica L, additional, Miller, Bess, additional, Brenchley, Jason, additional, Rosshart, Stephan P, additional, Rehermann, Barbara, additional, Doorbar, John, additional, Ta'ala, Blake A, additional, Pletnikova, Olga, additional, Troncoso, Juan C, additional, Resnick, Susan M, additional, Bolduc, Ben, additional, Sullivan, Matthew B, additional, Varsani, Arvind, additional, Segall, Anca M, additional, and Buck, Christopher B, additional

Published
2020
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43. The deaminase APOBEC3B triggers the death of cells lacking uracil DNA glycosylase

Author

Serebrenik, Artur A, Starrett, Gabriel J, Leenen, Sterre, Jarvis, Matthew C, Shaban, Nadine M, Salamango, Daniel J, Nilsen, Hilde, Brown, William L, Harris, Reuben S, Serebrenik, Artur A, Starrett, Gabriel J, Leenen, Sterre, Jarvis, Matthew C, Shaban, Nadine M, Salamango, Daniel J, Nilsen, Hilde, Brown, William L, and Harris, Reuben S

Abstract

Human cells express up to 9 active DNA cytosine deaminases with functions in adaptive and innate immunity. Many cancers manifest an APOBEC mutation signature and APOBEC3B (A3B) is likely the main enzyme responsible. Although significant numbers of APOBEC signature mutations accumulate in tumor genomes, the majority of APOBEC-catalyzed uracil lesions are probably counteracted in an error-free manner by the uracil base excision repair pathway. Here, we show that A3B-expressing cells can be selectively killed by inhibiting uracil DNA glycosylase 2 (UNG) and that this synthetic lethal phenotype requires functional mismatch repair (MMR) proteins and p53. UNG knockout human 293 and MCF10A cells elicit an A3B-dependent death. This synthetic lethal phenotype is dependent on A3B catalytic activity and reversible by UNG complementation. A3B expression in UNG-null cells causes a buildup of genomic uracil, and the ensuing lethality requires processing of uracil lesions (likely U/G mispairs) by MSH2 and MLH1 (likely noncanonical MMR). Cancer cells expressing high levels of endogenous A3B and functional p53 can also be killed by expressing an UNG inhibitor. Taken together, UNG-initiated base excision repair is a major mechanism counteracting genomic mutagenesis by A3B, and blocking UNG is a potential strategy for inducing the selective death of tumors.

Published
2019

44. Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution

Author

Peretti, Alberto, Geoghegan, Eileen M., Pastrana, Diana V., Smola, Sigrun, Feld, Pascal, Sauter, Marlies, Lohse, Stefan, Ramesh, Mayur, Lim, Efrem S., Wang, David, Borgogna, Cinzia, FitzGerald, Peter C., Bliskovsky, Valery, Starrett, Gabriel J., Law, Emily K., Harris, Reuben S., Killian, J. Keith, Zhu, Jack, Pineda, Marbin, Meltzer, Paul S., Boldorini, Renzo, Gariglio, Marisa, and Buck, Christopher B.

Published
2018
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45. Metagenomic discovery of 83 new human papillomavirus types in patients with immunodeficiency

Author

Pastrana, Diana V., Peretti, Alberto, Welch, Nicole L., Borgogna, Cinzia, Olivero, Carlotta, Badolato, Raffaele, Notarangelo, Lucia D., Gariglio, Marisa, FitzGerald, Peter C., McIntosh, Carl E., Reeves, Jesse, Starrett, Gabriel J., Bliskovsky, Valery, Velez, Daniel, Brownell, Isaac, Yarchoan, Robert, Wyvill, Kathleen M., Uldrick, Thomas S., Maldarelli, Frank, Lisco, Andrea, Sereti, Irini, Gonzalez, Christopher M., Androphy, Elliot J., McBride, Alison A., Van Doorslaer, Koenraad, Garcia, Francisco, Dvoretzky, Israel, Liu, Joceline S., Han, Justin, Murphy, Philip M., McDermott, David H., Buck, Christopher B., and Imperiale, Michael J.

Subjects
0301 basic medicine, Male, Gammapapillomavirus, Skin swabs, lcsh:QR1-502, lcsh:Microbiology, Clinical Science and Epidemiology, Hypogammaglobulinemia, 0302 clinical medicine, 80 and over, Viral, Epidermodysplasia verruciformis, Gammapapillomaviruses, Metagenomic, Next-generation sequencing, Plerixafor, WHIM syndrome, Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, DNA, Viral, Female, Genome, Viral, High-Throughput Nucleotide Sequencing, Humans, Immunologic Deficiency Syndromes, Metagenomics, Middle Aged, Mucous Membrane, Nucleic Acid Amplification Techniques, Papillomaviridae, Papillomavirus Infections, Skin, Young Adult, Immunodeficiency, Genome, integumentary system, medicine.diagnostic_test, virus diseases, QR1-502, 030220 oncology & carcinogenesis, Research Article, Microbiology, Deep sequencing, 03 medical and health sciences, Biopsy, medicine, Preschool, Molecular Biology, Myelokathexis, business.industry, DNA, medicine.disease, 030104 developmental biology, Immunology, business
Abstract

Although some members of the viral family Papillomaviridae cause benign skin warts (papillomas), many human papillomavirus (HPV) infections are not associated with visible symptoms. For example, most healthy adults chronically shed Gammapapillomavirus (Gamma) virions from apparently healthy skin surfaces. To further explore the diversity of papillomaviruses, we performed viromic surveys on immunodeficient individuals suffering from florid skin warts. Our results nearly double the number of known Gamma HPV types and suggest that WHIM syndrome patients are uniquely susceptible to Gamma HPV-associated skin warts. Preliminary results suggest that treatment with the drug plerixafor may promote resolution of the unusual Gamma HPV skin warts observed in WHIM patients., Several immunodeficiencies are associated with high susceptibility to persistent and progressive human papillomavirus (HPV) infection leading to a wide range of cutaneous and mucosal lesions. However, the HPV types most commonly associated with such clinical manifestations in these patients have not been systematically defined. Here, we used virion enrichment, rolling circle amplification, and deep sequencing to identify circular DNA viruses present in skin swabs and/or wart biopsy samples from 48 patients with rare genetic immunodeficiencies, including patients with warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome, or epidermodysplasia verruciformis (EV). Their profiles were compared with the profiles of swabs from 14 healthy adults and warts from 6 immunologically normal children. Individual patients were typically infected with multiple HPV types; up to 26 different types were isolated from a single patient (multiple anatomical sites, one time point). Among these, we identified the complete genomes of 83 previously unknown HPV types and 35 incomplete genomes representing possible additional new types. HPV types in the genus Gammapapillomavirus were common in WHIM patients, whereas EV patients mainly shed HPVs from the genus Betapapillomavirus. Preliminary evidence based on three WHIM patients treated with plerixafor, a leukocyte mobilizing agent, suggest that longer-term therapy may correlate with decreased HPV diversity and increased predominance of HPV types associated with childhood skin warts. IMPORTANCE Although some members of the viral family Papillomaviridae cause benign skin warts (papillomas), many human papillomavirus (HPV) infections are not associated with visible symptoms. For example, most healthy adults chronically shed Gammapapillomavirus (Gamma) virions from apparently healthy skin surfaces. To further explore the diversity of papillomaviruses, we performed viromic surveys on immunodeficient individuals suffering from florid skin warts. Our results nearly double the number of known Gamma HPV types and suggest that WHIM syndrome patients are uniquely susceptible to Gamma HPV-associated skin warts. Preliminary results suggest that treatment with the drug plerixafor may promote resolution of the unusual Gamma HPV skin warts observed in WHIM patients.

Published
2018

46. APOBEC3A Catalyzes Mutation and Drives CarcinogenesisIn Vivo

Author

Law, Emily K., primary, Levin-Klein, Rena, additional, Jarvis, Matthew C., additional, Kim, Hyoung, additional, Argyris, Prokopios P., additional, Carpenter, Michael A., additional, Starrett, Gabriel J., additional, Larson, Lindsay K., additional, Burns, Michael B., additional, Vogel, Rachel I., additional, Stavrou, Spyridon, additional, Aguilera, Alexya N., additional, Wagner, Sandra, additional, Largaespada, David A., additional, Starr, Timothy K., additional, Ross, Susan R., additional, and Harris, Reuben S., additional

Published
2019
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48. Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma

Author

Starrett, Gabriel J., primary, Thakuria, Manisha, additional, Chen, Tianqi, additional, Marcelus, Christina, additional, Cheng, Jingwei, additional, Nomburg, Jason, additional, Thorner, Aaron R., additional, Slevin, Michael K., additional, Powers, Winslow, additional, Burns, Robert T., additional, Perry, Caitlin, additional, Piris, Adriano, additional, Kuo, Frank C., additional, Rabinowits, Guilherme, additional, Giobbie-Hurder, Anita, additional, MacConaill, Laura E., additional, and DeCaprio, James A., additional

Published
2019
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50. Polyomavirus T Antigen InducesAPOBEC3BExpression Using an LXCXE-Dependent and TP53-Independent Mechanism

Author

Starrett, Gabriel J., primary, Serebrenik, Artur A., additional, Roelofs, Pieter A., additional, McCann, Jennifer L., additional, Verhalen, Brandy, additional, Jarvis, Matthew C., additional, Stewart, Teneale A., additional, Law, Emily K., additional, Krupp, Annabel, additional, Jiang, Mengxi, additional, Martens, John W. M., additional, Cahir-McFarland, Ellen, additional, Span, Paul N., additional, and Harris, Reuben S., additional

Published
2019
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