Single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) is rapidly becoming a powerful technology for assessing the epigenetic landscape of thousands of cells. However, the sparsity of the resulting data poses significant challenges to their interpretability and informativeness. Different computational methods are available, proposing ways to generate significant features from accessibility data and process them to obtain meaningful results. Foremost among them is the peak calling, which interprets the raw scATAC-seq data generating the peaks as features. However, scATAC-seq data are not trivially comparable with single-cell RNA sequencing (scRNA-seq) data, an increasingly pressing challenge since the necessity of multimodal experiments integration. For this reason, this study wants to improve the concept of the Gene Activity Matrix (GAM), which links the accessibility data to the genes, by proposing an improved version of the Genomic-Annotated Gene Activity Matrix (GAGAM) concept. Specifically, this paper presents GAGAM v1.2, a new and better version of GAGAM v1.0. GAGAM aims to label the peaks and link them to the genes through functional annotation of the whole genome. Using genes as features in scATAC-seq datasets makes different datasets comparable and allows linking gene accessibility and expression. This link is crucial for gene regulation understanding and fundamental for the increasing impact of multi-omics data. Results confirm that our method performs better than the previous GAMs and shows a preliminary comparison with scRNA-seq data.
Single-cell Assay for Transposase Accessible Chromatin using sequencing (scATAC-seq) is rapidly becoming a powerful technology to assess the epigenetic landscape of thousands of cells. However, the current great sparsity of the resulting data poses significant challenges to their interpretability and informativeness. Different computational methods are available, proposing ways to generate significant features from accessibility data and process them to obtain meaningful results. In particular, the most common way to interpret the raw scATAC-seq data is through peak-calling, generating the peaks as features. Nevertheless, this method is dataset-dependent because the peaks are related to the given dataset and can not be directly compared between different experiments. For this reason, this study wants to improve on the concept of the Gene Activity Matrix (GAM), which links the accessibility data to the genes, by proposing a Genomic-Annotated Gene Activity Matrix (GAGAM), which aims to label the peaks and link them to the genes through functional annotation of the whole genome. Using genes as features solves the problem of the feature dataset dependency allowing for the link of gene accessibility and expression. The latter is crucial for gene regulation understanding and fundamental for the increasing impact of multi-omics data. Results confirm that our method performs better than the previous GAMs.
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