提出可解释的单细胞罕见细胞检测框架,让异常细胞的基因依据一目了然。
A New Framework for Explainable Rare Cell Identification in Single-Cell Transcriptomics Data
- 跳过主成分分析,直接在原始基因表达上检测异常细胞。
- 识别出罕见细胞,并定位使其异常的关键基因子空间。
- 适合关注机制解释的生物医学研究者使用。
单细胞转录组数据中罕见细胞类型的检测对阐明疾病发生机制和组织发育动态至关重要。然而,现有方法普遍存在无法基于基因提供每个被识别为罕见细胞的解释这一关键缺陷。我们识别出三个主要原因:第一,异常检测器常为“黑箱”,能发现异常但无法说明为何异常;第二,标准分析流程依赖主成分分析(PCA)等降维技术,将有意义的基因表达转化为抽象不可解释的特征;第三,现有解释算法难以应用于该领域,因单细胞数据具有高维度、噪声大和高度稀疏等特点。为此,我们提出一种可解释的单细胞转录组异常检测框架,不仅能识别个体异常细胞,还能基于相关基因提供可视化解释。该框架包含两项现有方法未具备的核心要素:一是摒弃了以往研究中视为必要步骤的PCA;二是采用前沿的异常检测器与解释器,高效准确地定位每例罕见细胞及其邻近正常细胞所对应的基因子空间,实现对每个罕见细胞及对应正常细胞的解释。
原文摘要 · Abstract (English)
The detection of rare cell types in single-cell transcriptomics data is crucial for elucidating disease pathogenesis and tissue development dynamics. However, a critical gap that persists in current methods is their inability to provide an explanation based on genes for each cell they have detected as rare. We identify three primary sources of this deficiency. First, the anomaly detectors often function as "black boxes", designed to detect anomalies but unable to explain why a cell is anomalous. Second, the standard analytical framework hinders interpretability by relying on dimensionality reduction techniques, such as Principal Component Analysis (PCA), which transform meaningful gene expression data into abstract, uninterpretable features. Finally, existing explanation algorithms cannot be readily applied to this domain, as single-cell data is characterized by high dimensionality, noise, and substantial sparsity. To overcome these limitations, we introduce a framework for explainable anomaly detection in single-cell transcriptomics data which not only identifies individual anomalies, but also provides a visual explanation based on genes that makes an instance anomalous. This framework has two key ingredients that are not existed in current methods applied in this domain. First, it eliminates the PCA step which is deemed to be an essential component in previous studies. Second, it employs the state-of-art anomaly detector and explainer as the efficient and effective means to find each rare cell and the relevant gene subspace in order to provide explanations for each rare cell as well as the typical normal cell associated with the rare cell's closest normal cells.
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