A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis.

Journal: Cancer research
PMID: 39082680

Abstract

Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response. In this study, we developed an extensive, pan-cancer repository of >1,000 PDX and paired parental tumor H&E images. These images, curated from the PDX Development and Trial Centers Research Network Consortium, had a range of associated genomic and transcriptomic data, clinical metadata, pathologic assessments of cell composition, and, in several cases, detailed pathologic annotations of neoplastic, stromal, and necrotic regions. The amenability of these images to deep learning was highlighted through three applications: (i) development of a classifier for neoplastic, stromal, and necrotic regions; (ii) development of a predictor of xenograft-transplant lymphoproliferative disorder; and (iii) application of a published predictor of microsatellite instability. Together, this PDX Development and Trial Centers Research Network image repository provides a valuable resource for controlled digital pathology analysis, both for the evaluation of technical issues and for the development of computational image-based methods that make clinical predictions based on PDX treatment studies. Significance: A pan-cancer repository of >1,000 patient-derived xenograft hematoxylin and eosin-stained images will facilitate cancer biology investigations through histopathologic analysis and contributes important model system data that expand existing human histology repositories.

Authors

  • Brian S White
    The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr., Farmington, CT, 06032, USA.
  • Xing Yi Woo
    The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
  • Soner Koc
    Department of Computer Engineering, Koç University, Istanbul, Turkey.
  • Todd Sheridan
    The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
  • Steven B Neuhauser
    The Jackson Laboratory, Bar Harbor, Maine.
  • Shidan Wang
    Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, 5325 Harry Hines Blvd, Dallas, TX, 75390, USA.
  • Yvonne A Evrard
    Developmental Therapeutics Branch, National Cancer Institute, Frederick, MD, USA.
  • Li Chen
    Department of Endocrinology and Metabolism, Qilu Hospital, Shandong University, Jinan, China.
  • Ali Foroughi Pour
    The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • John D Landua
    Baylor College of Medicine, Houston, Texas.
  • R Jay Mashl
    Washington University School of Medicine, St. Louis, Missouri.
  • Sherri R Davies
    Washington University School of Medicine, St. Louis, Missouri.
  • Bingliang Fang
    University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Maria Gabriela Raso
    University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Kurt W Evans
    University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Matthew H Bailey
    Simmons Center for Cancer Research, Brigham Young University, Provo, Utah.
  • Yeqing Chen
    The Wistar Institute, Philadelphia, Pennsylvania.
  • Min Xiao
  • Jill C Rubinstein
    The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
  • Brian J Sanderson
    The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
  • Michael W Lloyd
    The Jackson Laboratory, Bar Harbor, Maine.
  • Sergii Domanskyi
    The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
  • Lacey E Dobrolecki
    Baylor College of Medicine, Houston, Texas.
  • Maihi Fujita
    Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
  • Junya Fujimoto
    Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX.
  • Guanghua Xiao
  • Ryan C Fields
    Washington University School of Medicine, St. Louis, Missouri.
  • Jacqueline L Mudd
    Washington University School of Medicine, St. Louis, Missouri.
  • Xiaowei Xu
    Department of Information Science, University of Arkansas, Little Rock, Arkansas, United States of America.
  • Melinda G Hollingshead
    National Cancer Institute, Bethesda, Maryland.
  • Shahanawaz Jiwani
    Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
  • Saul Acevedo
    Velsera, Charlestown, Massachusetts.
  • Brandi N Davis-Dusenbery
    Velsera, Charlestown, Massachusetts.
  • Peter N Robinson
    The Jackson Laboratory for Genomic Medicine Farmington CT 06032 USA.
  • Jeffrey A Moscow
    National Cancer Institute, Bethesda, Maryland.
  • James H Doroshow
    Developmental Therapeutics Branch, National Cancer Institute, Frederick, MD, USA.
  • Nicholas Mitsiades
    Baylor College of Medicine, Houston, Texas.
  • Salma Kaochar
    Baylor College of Medicine, Houston, Texas.
  • Chong-Xian Pan
    University of California, Davis, Davis, California.
  • Luis G Carvajal-Carmona
    University of California, Davis, Davis, California.
  • Alana L Welm
    Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
  • Bryan E Welm
    Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
  • Ramaswamy Govindan
    Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
  • Shunqiang Li
    Washington University School of Medicine, St. Louis, Missouri.
  • Michael A Davies
    University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Jack A Roth
    Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Funda Meric-Bernstam
    Center for Computational Biomedicine, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA, Department of Public Health Science, Medical University of South Carolina, 135 Cannon Street, Suite 303, Charleston, SC 29425, USA and Department of Investigational Cancer Therapeutics, Institute for Personalized Cancer Therapy, UT-MD Anderson Cancer Center, 1400 Holcombe Blvd., FC8.3044, Houston, TX 77030, USA.
  • Yang Xie
    Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, 5325 Harry Hines Blvd, Dallas, TX, 75390, USA.
  • Meenhard Herlyn
    The Wistar Institute, Philadelphia, Pennsylvania.
  • Li Ding
    College of Chemistry and Food Engineering, Changsha University of Science and Technology, Changsha 410014, China.
  • Michael T Lewis
    Baylor College of Medicine, Houston, Texas.
  • Carol J Bult
    The Jackson Laboratory, Bar Harbor, ME, USA.
  • Dennis A Dean
    Velsera, Charlestown, Massachusetts.
  • Jeffrey H Chuang
    The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. Jeff.Chuang@jax.org.

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