Multiplexed single-cell morphometry for hematopathology diagnostics

Albert G. Tsai, David R. Glass, Marisa Juntilla, Felix J. Hartmann, Jean S. Oak, Sebastian Fernandez-Pol, Robert S. Ohgami, Sean C. Bendall

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The diagnosis of lymphomas and leukemias requires hematopathologists to integrate microscopically visible cellular morphology with antibody-identified cell surface molecule expression. To merge these into one high-throughput, highly multiplexed, single-cell assay, we quantify cell morphological features by their underlying, antibody-measurable molecular components, which empowers mass cytometers to ‘see’ like pathologists. When applied to 71 diverse clinical samples, single-cell morphometric profiling reveals robust and distinct patterns of ‘morphometric’ markers for each major cell type. Individually, lamin B1 highlights acute leukemias, lamin A/C helps distinguish normal from neoplastic mature T cells, and VAMP-7 recapitulates light-cytometric side scatter. Combined with machine learning, morphometric markers form intuitive visualizations of normal and neoplastic cellular distribution and differentiation. When recalibrated for myelomonocytic blast enumeration, this approach is superior to flow cytometry and comparable to expert microscopy, bypassing years of specialized training. The contextualization of traditional surface markers on independent morphometric frameworks permits more sensitive and automated diagnosis of complex hematopoietic diseases.

Original languageEnglish (US)
Pages (from-to)408-417
Number of pages10
JournalNature medicine
Volume26
Issue number3
DOIs
StatePublished - Mar 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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