Highly multiplexed immunofluorescence imaging of human tissues and tumors using t-CyCIF and conventional optical microscopes
Jia-Ren Lin,Benjamin Izar,Shu Wang,Clarence Yapp,Shaolin Mei,Parin Shah,Sandro Santagata,Peter K. Sorger +7 more
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TLDR
Tissue-based cyclic immunofluorescence method for highly multiplexed immuno-fluorescence imaging of formalin-fixed, paraffin-embedded specimens mounted on glass slides, the most widely used specimens for histopathological diagnosis of cancer and other diseases is described.Abstract:
The architecture of normal and diseased tissues strongly influences the development and progression of disease as well as responsiveness and resistance to therapy We describe a tissue-based cyclic immunofluorescence (t-CyCIF) method for highly multiplexed immuno-fluorescence imaging of formalin-fixed, paraffin-embedded (FFPE) specimens mounted on glass slides, the most widely used specimens for histopathological diagnosis of cancer and other diseases t-CyCIF generates up to 60-plex images using an iterative process (a cycle) in which conventional low-plex fluorescence images are repeatedly collected from the same sample and then assembled into a high-dimensional representation t-CyCIF requires no specialized instruments or reagents and is compatible with super-resolution imaging; we demonstrate its application to quantifying signal transduction cascades, tumor antigens and immune markers in diverse tissues and tumors The simplicity and adaptability of t-CyCIF makes it an effective method for pre-clinical and clinical research and a natural complement to single-cell genomicsread more
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The somatic genomic landscape of glioblastoma
Cameron Brennan,Roel G.W. Verhaak,Aaron McKenna,Benito Campos,Houtan Noushmehr,Sofie R. Salama,Siyuan Zheng,Debyani Chakravarty,J. Zachary Sanborn,Samuel H. Berman,Rameen Beroukhim,Brady Bernard,Chang-Jiun Wu,Giannicola Genovese,Ilya Shmulevich,Jill S. Barnholtz-Sloan,Lihua Zou,Rahulsimham Vegesna,Sachet A. Shukla,Giovanni Ciriello,W. K. Yung,Wei Zhang,Carrie Sougnez,Tom Mikkelsen,Kenneth Aldape,Darell D. Bigner,Erwin G. Van Meir,Michael D. Prados,Andrew E. Sloan,Keith L. Black,Jennifer M. Eschbacher,Gaetano Finocchiaro,William A. Friedman,David W. Andrews,Abhijit Guha,Mary Iacocca,Brian P. O'Neil,Greg Foltz,Jerome Myers,Daniel J. Weisenberger,Robert Penny,Raju Kucherlapati,Charles M. Perou,D. Neil Hayes,Richard A. Gibbs,Marco A. Marra,Gordon B. Mills,Eric S. Lander,Paul T. Spellman,Richard K. Wilson,Chris Sander,John N. Weinstein,Matthew Meyerson,Stacey Gabriel,Peter W. Laird,David Haussler,Gad Getz,Lynda Chin +57 more
TL;DR: In this article, the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs) was described, including several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA.
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Itay Tirosh,Benjamin Izar,Daniel J. Treacy,John J. Trombetta,Asaf Rotem,Christopher Rodman,Christine G. Lian,George F. Murphy,Mohammad Fallahi-Sichani,Ken Dutton-Regester,Jia-Ren Lin,Ofir Cohen,Parin Shah,Diana Lu,Alexandra-Chloé Villani,Aleksandr Andreev,E.M. Van Allen,Monica M. Bertagnolli,Peter K. Sorger,Ryan J. Sullivan,Keith T. Flaherty,Dennie T. Frederick,Judit Jané-Valbuena,Orit Rozenblatt-Rosen,Sanjay M. Prakadan,Marc H. Wadsworth,Alex S. Genshaft,Travis K. Hughes,Carly G. K. Ziegler,Samuel W. Kazer,Alethe Gaillard de Saint Germain,Kellie E. Kolb,Cory M. Johannessen,Clifford H. Yoon,Alex K. Shalek,Aviv Regev,Levi A. Garraway +36 more
TL;DR: Tirosh et al. as discussed by the authors applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells.
Journal ArticleDOI
A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade
Livnat Jerby-Arnon,Parin Shah,Michael S. Cuoco,Christopher Rodman,Mei-Ju Su,Johannes C. Melms,Rachel Leeson,Abhay Kanodia,Shaolin Mei,Jia-Ren Lin,Shu Wang,Bokang Rabasha,David Liu,Gao Zhang,Claire Margolais,Orr Ashenberg,Patrick A. Ott,Elizabeth I. Buchbinder,Rizwan Haq,F. Stephen Hodi,Genevieve M. Boland,Ryan J. Sullivan,Dennie T. Frederick,Benchun Miao,Tabea Moll,Keith T. Flaherty,Meenhard Herlyn,Russell W. Jenkins,Rohit Thummalapalli,Monika S. Kowalczyk,Israel Cañadas,Bastian Schilling,Bastian Schilling,Adam N.R. Cartwright,Adrienne M. Luoma,Shruti Malu,Patrick Hwu,Chantale Bernatchez,Marie Andrée Forget,David A. Barbie,Alex K. Shalek,Itay Tirosh,Peter K. Sorger,Kai W. Wucherpfennig,Eliezer M. Van Allen,Dirk Schadendorf,Bruce E. Johnson,Asaf Rotem,Asaf Rotem,Orit Rozenblatt-Rosen,Levi A. Garraway,Charles H. Yoon,Charles H. Yoon,Benjamin Izar,Aviv Regev +54 more
TL;DR: A resistance program expressed by malignant cells that is associated with T cell exclusion and immune evasion is identified, and this study provides a high-resolution landscape of ICI-resistant cell states, identifies clinically predictive signatures, and suggests new therapeutic strategies to overcome immunotherapy resistance.
Journal ArticleDOI
SARS-CoV-2 infection protects against rechallenge in rhesus macaques.
Abishek Chandrashekar,Jinyan Liu,Amanda J. Martinot,Amanda J. Martinot,Katherine McMahan,Noe B. Mercado,Lauren Peter,Lisa H. Tostanoski,Jingyou Yu,Zoltan Maliga,Michael Nekorchuk,Kathleen Busman-Sahay,Margaret Terry,Linda M. Wrijil,Sarah Ducat,David R. Martinez,Caroline Atyeo,Caroline Atyeo,Stephanie Fischinger,John S. Burke,Matthew D. Slein,Laurent Pessaint,Alex Van Ry,Jack Greenhouse,Tammy Taylor,Kelvin Blade,Anthony Cook,Brad Finneyfrock,Renita Brown,Elyse Teow,Jason Velasco,Roland Zahn,Frank Wegmann,Peter Abbink,Esther A. Bondzie,Gabriel Dagotto,Gabriel Dagotto,Makda S. Gebre,Makda S. Gebre,Xuan He,Catherine Jacob-Dolan,Catherine Jacob-Dolan,Nicole Kordana,Zhenfeng Li,Michelle A. Lifton,Shant H. Mahrokhian,Lori F. Maxfield,Ramya Nityanandam,Joseph P. Nkolola,Aaron G. Schmidt,Andrew D. Miller,Ralph S. Baric,Galit Alter,Peter K. Sorger,Jacob D. Estes,Hanne Andersen,Mark G. Lewis,Dan H. Barouch,Dan H. Barouch +58 more
TL;DR: Data show that SARS-CoV-2 infection induced protective immunity against reexposure in nonhuman primates, and these findings have key implications for public health and economic initiatives if validated in human studies.
Journal ArticleDOI
Deep learning for cellular image analysis
TL;DR: The intersection between deep learning and cellular image analysis is reviewed and an overview of both the mathematical mechanics and the programming frameworks of deep learning that are pertinent to life scientists are provided.
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