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CHETAH: a selective, hierarchical cell type identification method for single-cell RNA sequencing

Jurrian K. de Kanter, View ORCID ProfilePhilip Lijnzaad, Tito Candelli, Thanasis Margaritis, Frank C.P. Holstege
doi: https://doi.org/10.1101/558908
Jurrian K. de Kanter
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
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Philip Lijnzaad
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
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  • ORCID record for Philip Lijnzaad
Tito Candelli
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
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Thanasis Margaritis
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
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Frank C.P. Holstege
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
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  • For correspondence: f.c.p.holstege@prinsesmaximacentrum.nl
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ABSTRACT

Cell type identification is essential for single-cell RNA sequencing (scRNA-seq) studies that are currently transforming the life sciences. CHETAH (CHaracterization of cEll Types Aided by Hierarchical clustering) is an accurate cell type identification algorithm that is rapid and selective, including the possibility of intermediate or unassigned categories. Evidence for assignment is based on a classification tree of previously available scRNA-seq reference data and includes a confidence score based on the variance in gene expression per cell type. For cell types represented in the reference data, CHETAH’s accuracy is as good as existing methods. Its specificity is superior when cells of an unknown type are encountered, such as malignant cells in tumor samples which it pinpoints as intermediate or unassigned. Although designed for tumor samples in particular, the use of unassigned and intermediate types is also valuable in other exploratory studies. This is exemplified in pancreas datasets where CHETAH highlights cell populations not well represented in the reference dataset, including cells with profiles that lie on a continuum between that of acinar and ductal cell types. Having the possibility of unassigned and intermediate cell types is pivotal for preventing misclassification and can yield important biological information for previously unexplored tissues.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 22, 2019.
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CHETAH: a selective, hierarchical cell type identification method for single-cell RNA sequencing
Jurrian K. de Kanter, Philip Lijnzaad, Tito Candelli, Thanasis Margaritis, Frank C.P. Holstege
bioRxiv 558908; doi: https://doi.org/10.1101/558908
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CHETAH: a selective, hierarchical cell type identification method for single-cell RNA sequencing
Jurrian K. de Kanter, Philip Lijnzaad, Tito Candelli, Thanasis Margaritis, Frank C.P. Holstege
bioRxiv 558908; doi: https://doi.org/10.1101/558908

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