SYLARAS: A Platform for the Statistical Analysis and Visual Display of Systemic Immunoprofiling Data and Its Application to Glioblastoma

Gregory J Baker; Jeremy L Muhlich; Sucheendra K Palaniappan; Jodene K Moore; Stephanie H Davis; Sandro Santagata; Peter K Sorger

doi:10.1016/j.cels.2020.08.001

SYLARAS: A Platform for the Statistical Analysis and Visual Display of Systemic Immunoprofiling Data and Its Application to Glioblastoma

Cell Syst. 2020 Sep 23;11(3):272-285.e9. doi: 10.1016/j.cels.2020.08.001. Epub 2020 Sep 7.

Authors

Gregory J Baker¹, Jeremy L Muhlich², Sucheendra K Palaniappan³, Jodene K Moore⁴, Stephanie H Davis⁵, Sandro Santagata⁶, Peter K Sorger⁷

Affiliations

¹ Laboratory of Systems Pharmacology, Program in Therapeutic Science, Harvard Medical School, Boston, MA 02115, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA 02115, USA. Electronic address: gregory_baker2@hms.harvard.edu.
² Laboratory of Systems Pharmacology, Program in Therapeutic Science, Harvard Medical School, Boston, MA 02115, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
³ Systems Biology Institute, Tokyo 141-0022, Japan.
⁴ Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
⁵ Laboratory of Systems Pharmacology, Program in Therapeutic Science, Harvard Medical School, Boston, MA 02115, USA.
⁶ Laboratory of Systems Pharmacology, Program in Therapeutic Science, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA 02115, USA; Department of Oncologic Pathology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
⁷ Laboratory of Systems Pharmacology, Program in Therapeutic Science, Harvard Medical School, Boston, MA 02115, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA 02115, USA. Electronic address: peter_sorger@hms.harvard.edu.

Abstract

Accurately profiling systemic immune responses to cancer initiation and progression is necessary for understanding tumor surveillance and, ultimately, improving therapy. Here, we describe the SYLARAS software tool (systemic lymphoid architecture response assessment) and a dataset collected with SYLARAS that describes the frequencies of immune cells in primary and secondary lymphoid organs and in the tumor microenvironment of mice engrafted with a standard syngeneic glioblastoma (GBM) model. The data resource involves profiles of 5 lymphoid tissues in 48 mice and shows that GBM causes wide-spread changes in the local and systemic immune architecture. We use SYLARAS to identify a subset of CD45R/B220⁺ CD8⁺ T cells that is depleted from circulation but accumulates in the tumor mass and confirm this finding using multiplexed immunofluorescence microscopy. SYLARAS is freely available for download at (https://github.com/gjbaker/sylaras). A record of this paper's transparent peer review process is included in the Supplemental Information.

Keywords: SYLARAS; computational flow cytometry; glioblastoma; systemic immunoprofiling; systems immunology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Neoplasms / epidemiology*
Brain Neoplasms / immunology*
Glioblastoma / epidemiology*
Glioblastoma / immunology*
Humans
Mice

Abstract

Publication types

MeSH terms

Grants and funding