HiCat融合有监督与无监督学习,精准识别单细胞数据中的新细胞类型。
HiCat: A Semi-Supervised Approach for Cell Type Annotation
- 结合参考数据与查询数据,用混合方法增强嵌入学习
- 在10个公开数据集上超越现有方法,能有效区分多个新细胞类型
- 适合生物医学研究者用于发现未知细胞亚群
我们提出HiCat(基于转化嵌入的混合细胞注释),一种新颖的半监督流程,用于从单细胞RNA测序数据中注释细胞类型。该方法融合已知细胞类型的有监督学习与发现新类型的无监督学习,结合参考数据和查询数据进行特征工程,提升嵌入学习效果,扩大无监督技术的有效样本量,并增强基于参考数据训练的监督模型在查询数据上的迁移能力。流程包含六个步骤:(1) 使用Harmony去除批次效应,生成50维主成分嵌入;(2) 通过UMAP降维至二维以捕捉关键数据模式;(3) 采用DBSCAN进行无监督聚类,得到一维聚类归属向量;(4) 合并多分辨率结果,构建涵盖参考与查询数据的53维特征空间;(5) 在参考数据上训练CatBoost模型,预测查询数据中的细胞类型;(6) 解决监督预测与无监督聚类标签间的不一致。在10个公开基因组数据集上的基准测试显示,HiCat在区分和识别多个新细胞类型方面优于其他方法,展现出其在复杂生物数据中的鲁棒性与适应性。
原文摘要 · Abstract (English)
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.
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