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  1. Article ; Online: Corrigendum: Blood, toil, and taxoteres: Biological determinants of treatment-induced ctDNA dynamics for interpreting tumor response.

    Boniface, Christopher T / Spellman, Paul T

    Pathology oncology research : POR

    2023  Volume 29, Page(s) 1611133

    Abstract: This corrects the article DOI: 10.3389/pore.2022.1610103.]. ...

    Abstract [This corrects the article DOI: 10.3389/pore.2022.1610103.].
    Language English
    Publishing date 2023-03-09
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 1375979-6
    ISSN 1532-2807 ; 1219-4956
    ISSN (online) 1532-2807
    ISSN 1219-4956
    DOI 10.3389/pore.2023.1611133
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  2. Article ; Online: Blood, toil, and taxoteres: Biological determinants of treatment-induced ctDNA dynamics for interpreting tumor response.

    Boniface, Christopher T / Spellman, Paul T

    Pathology oncology research : POR

    2022  Volume 28, Page(s) 1610103

    Abstract: Collection and analysis of circulating tumor DNA (ctDNA) is one of the few methods of liquid biopsy that measures generalizable and tumor specific molecules, and is one of the most promising approaches in assessing the effectiveness of cancer care. ... ...

    Abstract Collection and analysis of circulating tumor DNA (ctDNA) is one of the few methods of liquid biopsy that measures generalizable and tumor specific molecules, and is one of the most promising approaches in assessing the effectiveness of cancer care. Clinical assays that utilize ctDNA are commercially available for the identification of actionable mutations prior to treatment and to assess minimal residual disease after treatment. There is currently no clinical ctDNA assay specifically intended to monitor disease response during treatment, partially due to the complex challenge of understanding the biological sources of ctDNA and the underlying principles that govern its release. Although studies have shown pre- and post-treatment ctDNA levels can be prognostic, there is evidence that early, on-treatment changes in ctDNA levels are more accurate in predicting response. Yet, these results also vary widely among cohorts, cancer type, and treatment, likely due to the driving biology of tumor cell proliferation, cell death, and ctDNA clearance kinetics. To realize the full potential of ctDNA monitoring in cancer care, we may need to reorient our thinking toward the fundamental biological underpinnings of ctDNA release and dissemination from merely seeking convenient clinical correlates.
    MeSH term(s) Biomarkers, Tumor/genetics ; Circulating Tumor DNA/genetics ; Docetaxel ; Humans ; Liquid Biopsy/methods ; Mutation ; Neoplasm, Residual
    Chemical Substances Biomarkers, Tumor ; Circulating Tumor DNA ; Docetaxel (15H5577CQD)
    Language English
    Publishing date 2022-05-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1375979-6
    ISSN 1532-2807 ; 1219-4956
    ISSN (online) 1532-2807
    ISSN 1219-4956
    DOI 10.3389/pore.2022.1610103
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Defining clonal hematopoiesis of indeterminate potential: evolutionary dynamics and detection under aging and inflammation.

    Goldman, Elisabeth A / Spellman, Paul T / Agarwal, Anupriya

    Cold Spring Harbor molecular case studies

    2023  Volume 9, Issue 2

    Abstract: Clonal hematopoiesis (CH), in which hematopoietic stem and progenitor cell (HSPC) clones and their progeny expand in the circulating blood cell population, occurs following the acquisition of somatic driver mutations. Individuals diagnosed with clonal ... ...

    Abstract Clonal hematopoiesis (CH), in which hematopoietic stem and progenitor cell (HSPC) clones and their progeny expand in the circulating blood cell population, occurs following the acquisition of somatic driver mutations. Individuals diagnosed with clonal hematopoiesis of indeterminate potential (CHIP) carry somatic mutations in hematological malignancy-associated driver genes, historically at or above a variant allele frequency of 2%, but do not exhibit abnormal blood cell counts or any other symptoms of hematologic disease. However, CHIP is associated with moderately increased risk of hematological cancer and a greater likelihood of cardiovascular and pulmonary disease. Recent advances in the resolution of high-throughput sequencing experiments suggest CHIP is much more prevalent in the population than once thought, particularly among those aged 60 and over. Although CHIP does elevate the risk of eventual hematological malignancy, only one in 10 individuals with CHIP will receive such a diagnosis; the problem lies in the continued difficulty in accurately separating the 10% of CHIP patients who are most likely to be in a premalignant state from those who are not, given the heterogeneity of this condition and the etiology of the associated hematological cancers. Concerns over the risk of eventual malignancies must be balanced with growing recognition of CH as a common age-dependent occurrence, and efforts to better characterize and differentiate oncogenic clonal expansion from that which is much more benign. In this review, we discuss evolutionary dynamics of CH and CHIP, the relationship of CH to aging and inflammation, and the role of the epigenome in promoting potentially pathogenic or benign cellular trajectories. We outline molecular mechanisms that may contribute to heterogeneity in the etiology of CHIP and the incidence of malignant disease among individuals. Finally, we discuss epigenetic markers and modifications for CHIP detection and monitoring with the potential for translational applications and clinical utility in the near future.
    MeSH term(s) Humans ; Middle Aged ; Aged ; Clonal Hematopoiesis/genetics ; Mutation ; Hematopoiesis/genetics ; Neoplasms/genetics ; Aging/genetics ; Hematologic Neoplasms/diagnosis ; Hematologic Neoplasms/genetics ; Inflammation/genetics
    Language English
    Publishing date 2023-05-09
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 2835759-0
    ISSN 2373-2873 ; 2373-2873
    ISSN (online) 2373-2873
    ISSN 2373-2873
    DOI 10.1101/mcs.a006251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Alternative Splicing in Tumors - A Path to Immunogenicity?

    Slansky, Jill E / Spellman, Paul T

    The New England journal of medicine

    2019  Volume 380, Issue 9, Page(s) 877–880

    MeSH term(s) Alternative Splicing ; Antigens/genetics ; Antigens/metabolism ; Bcl-2-Like Protein 11/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Immunogenetic Phenomena ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/metabolism
    Chemical Substances Antigens ; Bcl-2-Like Protein 11
    Language English
    Publishing date 2019-02-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMcibr1814237
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  5. Article ; Online: Differential Allelic Expression among Long Non-Coding RNAs.

    Heskett, Michael B / Spellman, Paul T / Thayer, Mathew J

    Non-coding RNA

    2021  Volume 7, Issue 4

    Abstract: Long non-coding RNAs (lncRNA) comprise a diverse group of non-protein-coding RNAs >200 bp in length that are involved in various normal cellular processes and disease states, and can affect coding gene expression through mechanisms ... ...

    Abstract Long non-coding RNAs (lncRNA) comprise a diverse group of non-protein-coding RNAs >200 bp in length that are involved in various normal cellular processes and disease states, and can affect coding gene expression through mechanisms in
    Language English
    Publishing date 2021-10-22
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2813993-8
    ISSN 2311-553X ; 2311-553X
    ISSN (online) 2311-553X
    ISSN 2311-553X
    DOI 10.3390/ncrna7040066
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  6. Article ; Online: Novel recruitment approaches and operational results for a statewide population Cohort for cancer research: The Healthy Oregon Project.

    Zhang, Zhenzhen / Shafer, Autumn / Johnson-Camacho, Katie / Adey, Andrew / Anur, Pavana / Brown, Kim A / Conrad, Casey / Crist, Rachel / Farris, Paige E / Harrington, Christina A / Marriott, Lisa K / Mitchell, Asia / O'Roak, Brian / Serrato, Vanessa / Richards, C Sue / Spellman, Paul T / Shannon, Jackilen

    Journal of clinical and translational science

    2024  Volume 8, Issue 1, Page(s) e32

    Abstract: Background: Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward ... ...

    Abstract Background: Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms.
    Methods: We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities.
    Results: By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18-100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ∼87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates.
    Conclusion: This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.
    Language English
    Publishing date 2024-01-19
    Publishing country England
    Document type Journal Article
    ISSN 2059-8661
    ISSN (online) 2059-8661
    DOI 10.1017/cts.2024.9
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  7. Article ; Online: An open protocol for modeling T Cell Clonotype repertoires using TCRβ CDR3 sequences.

    Gurun, Burcu / Horton, Wesley / Murugan, Dhaarini / Zhu, Biqing / Leyshock, Patrick / Kumar, Sushil / Byrne, Katelyn T / Vonderheide, Robert H / Margolin, Adam A / Mori, Motomi / Spellman, Paul T / Coussens, Lisa M / Speed, Terence P

    BMC genomics

    2023  Volume 24, Issue 1, Page(s) 349

    Abstract: T cell receptor repertoires can be profiled using next generation sequencing (NGS) to measure and monitor adaptive dynamical changes in response to disease and other perturbations. Genomic DNA-based bulk sequencing is cost-effective but necessitates ... ...

    Abstract T cell receptor repertoires can be profiled using next generation sequencing (NGS) to measure and monitor adaptive dynamical changes in response to disease and other perturbations. Genomic DNA-based bulk sequencing is cost-effective but necessitates multiplex target amplification using multiple primer pairs with highly variable amplification efficiencies. Here, we utilize an equimolar primer mixture and propose a single statistical normalization step that efficiently corrects for amplification bias post sequencing. Using samples analyzed by both our open protocol and a commercial solution, we show high concordance between bulk clonality metrics. This approach is an inexpensive and open-source alternative to commercial solutions.
    MeSH term(s) Base Sequence ; Chromosome Mapping ; High-Throughput Nucleotide Sequencing/methods ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; T-Lymphocytes
    Chemical Substances Receptors, Antigen, T-Cell, alpha-beta
    Language English
    Publishing date 2023-06-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041499-7
    ISSN 1471-2164 ; 1471-2164
    ISSN (online) 1471-2164
    ISSN 1471-2164
    DOI 10.1186/s12864-023-09424-z
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  8. Article: An open protocol for modeling T Cell Clonotype repertoires using TCRβ CDR3 sequences.

    Gurun, Burcu / Horton, Wesley / Murugan, Dhaarini / Zhu, Biqing / Leyshock, Patrick / Kumar, Sushil / Byrne, Katelyn T / Vonderheide, Robert H / Margolin, Adam A / Mori, Motomi / Spellman, Paul T / Coussens, Lisa M / Speed, Terence P

    Research square

    2023  

    Abstract: T cell receptor repertoires can be profiled using next generation sequencing (NGS) to measure and monitor adaptive dynamical changes in response to disease and other perturbations. Genomic DNA-based bulk sequencing is cost-effective but necessitates ... ...

    Abstract T cell receptor repertoires can be profiled using next generation sequencing (NGS) to measure and monitor adaptive dynamical changes in response to disease and other perturbations. Genomic DNA-based bulk sequencing is cost-effective but necessitates multiplex target amplification using multiple primer pairs with highly variable amplification efficiencies. Here, we utilize an equimolar primer mixture and propose a single statistical normalization step that efficiently corrects for amplification bias post sequencing. Using samples analyzed by both our open protocol and a commercial solution, we show high concordance between bulk clonality metrics. This approach is an inexpensive and open-source alternative to commercial solutions.
    Language English
    Publishing date 2023-02-16
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-2140339/v1
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  9. Article: Supervised learning of high-confidence phenotypic subpopulations from single-cell data.

    Ren, Tao / Chen, Canping / Danilov, Alexey V / Liu, Susan / Guan, Xiangnan / Du, Shunyi / Wu, Xiwei / Sherman, Mara H / Spellman, Paul T / Coussens, Lisa M / Adey, Andrew C / Mills, Gordon B / Wu, Ling-Yun / Xia, Zheng

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Accurately identifying phenotype-relevant cell subsets from heterogeneous cell populations is crucial for delineating the underlying mechanisms driving biological or clinical phenotypes. Here, by deploying a learning with rejection strategy, we developed ...

    Abstract Accurately identifying phenotype-relevant cell subsets from heterogeneous cell populations is crucial for delineating the underlying mechanisms driving biological or clinical phenotypes. Here, by deploying a learning with rejection strategy, we developed a novel supervised learning framework called PENCIL to identify subpopulations associated with categorical or continuous phenotypes from single-cell data. By embedding a feature selection function into this flexible framework, for the first time, we were able to select informative features and identify cell subpopulations simultaneously, which enables the accurate identification of phenotypic subpopulations otherwise missed by methods incapable of concurrent gene selection. Furthermore, the regression mode of PENCIL presents a novel ability for supervised phenotypic trajectory learning of subpopulations from single-cell data. We conducted comprehensive simulations to evaluate PENCIĽs versatility in simultaneous gene selection, subpopulation identification and phenotypic trajectory prediction. PENCIL is fast and scalable to analyze 1 million cells within 1 hour. Using the classification mode, PENCIL detected T-cell subpopulations associated with melanoma immunotherapy outcomes. Moreover, when applied to scRNA-seq of a mantle cell lymphoma patient with drug treatment across multiple time points, the regression mode of PENCIL revealed a transcriptional treatment response trajectory. Collectively, our work introduces a scalable and flexible infrastructure to accurately identify phenotype-associated subpopulations from single-cell data.
    Language English
    Publishing date 2023-03-25
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.23.533712
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Detecting cancer by monitoring circulating tumor DNA.

    Spellman, Paul T / Gray, Joe W

    Nature medicine

    2014  Volume 20, Issue 5, Page(s) 474–475

    MeSH term(s) Biomarkers, Tumor/blood ; Carcinoma, Non-Small-Cell Lung/diagnosis ; DNA, Neoplasm/isolation & purification ; Humans ; Neoplasms/diagnosis
    Chemical Substances Biomarkers, Tumor ; DNA, Neoplasm
    Language English
    Publishing date 2014-05-07
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/nm.3564
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