HiCat: A Semi-Supervised Approach for Cell Type Annotation

TL;DR

HiCat is a semi-supervised pipeline that combines supervised and unsupervised learning to improve cell type annotation in single-cell RNA sequencing data, especially for identifying novel cell types.

Contribution

It introduces a hybrid approach that fuses reference and query data for enhanced feature learning and transferability, outperforming existing methods on multiple datasets.

Findings

Outperforms existing methods in benchmarking tests

Accurately identifies multiple novel cell types

Enhances transferability of cell type predictions

Abstract

We introduce HiCat (Hybrid Cell Annotation using Transformative embeddings), a novel semi-supervised pipeline for annotating cell types from single-cell RNA sequencing data. HiCat fuses the strengths of supervised learning for known cell types with unsupervised learning to identify novel types. This hybrid approach incorporates both reference and query genomic data for feature engineering, enhancing the embedding learning process, increasing the effective sample size for unsupervised techniques, and improving the transferability of the supervised model trained on reference data when applied to query datasets. The pipeline follows six key steps: (1) removing batch effects using Harmony to generate a 50-dimensional principal component embedding; (2) applying UMAP for dimensionality reduction to two dimensions to capture crucial data patterns; (3) conducting unsupervised clustering of cells with DBSCAN, yielding a one-dimensional cluster membership vector; (4) merging the multi-resolution results of the previous steps into a 53-dimensional feature space that encompasses both reference and query data; (5) training a CatBoost model on the reference dataset to predict cell types in the query dataset; and (6) resolving inconsistencies between the supervised predictions and unsupervised cluster labels. When benchmarked on 10 publicly available genomic datasets, HiCat surpasses other methods, particularly in differentiating and identifying multiple new cell types. Its capacity to accurately classify novel cell types showcases its robustness and adaptability within intricate biological datasets.