Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens
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Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens
Yale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Uncovering I Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens Intratumoral And Intertumoral Heterogeneity AmongSingle-Cell Cancer SpecimensWilliam Shelton ChenFollow this and additional works at: https://elischolar.library.yale.edu/ymtdlRecommended CitationChen, William Shelton, 'Uncovering Intratumoral And Intertumoral Heterogeneity Among Single Cell Cancer S Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens pecimens’ (2020). Yale Medicine Thesis Digital Library. 3890.https://elischolar.library.yale.edu/ymtdl/3890This Open Access Thesis is brought to you fLuận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens
or free and open access by the School of Medicine at EliScholar - A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Uncovering I Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens re information, please contact elischoiar@yaie edu.Uncovering Intra tumoral and Intertumoral Heterogeneity Among Single-Cell Cancer SpecimensA Thesis Submitted to the Yale University School of Medicine in Partial Fulfillment of the Requirements for the Degree of Doctor of Medicineby William s. Chen Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens 2020UNCOVERING INTRATUMORAI. AND ĨNTERTUMORAL HETEROGENEITY AMONG SINGLE-CELL CANCER SPECIMENSWilliam s Chen. Ncveua Zivanovic. David V an Dijk. Guy WLuận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens
olf. Baud Bodcninillcr. and Simla Krisluiaswamy. Department of Gaieties, Yale Univ ersily. School of Medicine. New Haven. CT.ABSTRACTwhile several tooYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Uncovering I Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens ellular biospecmiens profiled at single-cell resolution. Developing such an approach is of great translational relevance and interest, as single-cell expression data are now often collected across numerous experimental conditions (e.g.. representing different drug perturbation conditions, CRISPR kno Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens ckdowns, or patients undergoing clinical trials) that need to be compared, hl this work. “Phenotypic Earth Moyer’s Distance" (P11EMD) IS presented asLuận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens
a solution to this problem. P11EMD is a general method for embedding a "manifold of manifolds,” in which each datapoint in the higher-level manifold (Yale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Uncovering I Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens mass cytometry drug screen experiment to map small-molecule inhibitors based on their differing effects on breast cancer cells undergoing epithelial-mesenchymal transition (LM1). llicsc experiments highlight EGFR and MF.K I 2 inhibitors as strongly halting EMT at an early stage and P13K m l OR Akl Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens inhibitors as enriching for a drug-resistant mesenchymal cell subtype characterized by high expression of phospho-S6. More generally, these experimentLuận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens
s reveal dial the final mapping of perturbation conditions has low inlrmsic dimension and that rhe network of drugs demonstrates manifold structure, pYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Uncovering I Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens l spectrum of perturbation effects could be learned by profiling just a small fraction (11%) of dings. Moreover. P11EMD could be integrated with complementary datasets to infer the phenotypes of biospeclinens not directly profiled with single-cell profiling. Together, these findings have major impli Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens cations for conducting future drug-screen expel iments. as they suggest that large-scale chug screens can be conducted by measuring only a small fractLuận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens
ion of the drugs using the most expensive high-throughput single-cell technologies—the effects of other drugs may be inferred by mapping and extendingYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Uncovering I Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens ar-cell renal cell carcinoma dataset (ccRCC). P11EMD maps tumors similarly to how it maps perturbation conditions as above 111 order to learn key axes along which tumors vary with respect to then tiunor-infiltrating immune cells. In both of these datasets. PhEMD highlights a subset of tumors demonst Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens rating a marked enrichment of exhausted CDS* T-cells The wide variability in tiunor-miiltrating immune cell abundance and particularly prominent exhauLuận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens
sted CD8* T-cell subpopulation highlights the importance of careful patient stratification when assessing clinical response to T cell-directed immunotYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Uncovering I Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens geometry of a large collection of single-cell biospecimens. Our varied experiments demonstrate that P11EMD is highly scalable, compatible with leading batch effect correction techniques, and generalizable to multiple experimental designs, with clear applicability to modem precision oncologyefforts.P Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens ublished in part:Chen ws*. Zivanovic N*. van Dijk D, Wolf G. Bodeiumller B. Krishnaswamy s. Uncovering axes of variation among single-cell cancer specLuận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens
imens. Nature Methods, 2020.Presented in part:Chen ws. Zivanovic N. Pe’er D. Bodeiunillei B. Krislinaswamy s. Phenotypic analysis of single-cell breasYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Uncovering I Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens shnaswamy and Bodenmiller laboratories for thought-provoking and productive discussions. I am especially appreciative of Prof. Sniita Krishnaswamy for her incredible mentorship and support. I am also indebted to Nevena Zivanovic and Bernd Bodenmiller for their help generating and interpreting much o Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens f the single-cell data presented in this work.Tills work was supported 111 part by the Chan-Zuckerberg Initiative Seed Networks for the Human Cell AtlLuận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens
as (S K ), a Swiss National Science Foundation (SNSF) R’Equip giant (B.B). a SN'SF Assistant Professorship giant PP00P3-144874 (B.B.). the SystemsX TrYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Uncovering I Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens Union s Seventh Framework Program (FP 2007-2013)/ERC Grant Agreement 336921 (B.B.). the CRƯKIMAXT Grand Challenge (B.B.). and the following National Institutes of Health (NIH) grants: RO 1 GM 135929 (S.K, G.W.). UC4 DK108132 (B.B.). NIH-NIDDK T35DK104689 (W.C.). Luận văn Thạc sĩ Uncovering Intratumoral And Intertumoral Heterogeneity Among SingleCell Cancer Specimens Yale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Uncovering IGọi ngay
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