RT Journal Article SR Electronic T1 HieRFIT: Hierarchical Random Forest for Information Transfer JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.09.16.300822 DO 10.1101/2020.09.16.300822 A1 Yasin Kaymaz A1 Florian Ganglberger A1 Ming Tang A1 Francesc Fernandez-Albert A1 Nathan Lawless A1 Timothy Sackton YR 2020 UL http://biorxiv.org/content/early/2020/09/18/2020.09.16.300822.abstract AB The emergence of single-cell RNA sequencing (scRNA-seq) has led to an explosion in novel methods to study biological variation among individual cells, and to classify cells into functional and biologically meaningful categories. Here, we present a new cell type projection tool, HieRFIT (Hierarchical Random Forest for Information Transfer), based on hierarchical random forests. HieRFIT uses a priori information about cell type relationships to improve classification accuracy, taking as input a hierarchical tree structure representing the class relationships, along with the reference data. We use an ensemble approach combining multiple random forest models, organized in a hierarchical decision tree structure. We show that our hierarchical classification approach improves accuracy and reduces incorrect predictions especially for inter-dataset tasks which reflect real life applications. We use a scoring scheme that adjusts probability distributions for candidate class labels and resolves uncertainties while avoiding the assignment of cells to incorrect types by labeling cells at internal nodes of the hierarchy when necessary. Using HieRFIT, we re-analyzed publicly available scRNA-seq datasets showing its effectiveness in cell type cross-projections with inter/intra-species examples. HieRFIT is implemented as an R package and it is available at (https://github.com/yasinkaymaz/HieRFIT/releases/tag/v1.0.0)Competing Interest StatementThe authors have declared no competing interest.