==== Front bioRxiv BIORXIV bioRxiv Cold Spring Harbor Laboratory 10.1101/2023.05.29.542760 preprint 1 Article Boosting Single-Cell RNA Sequencing Analysis with Simple Neural Attention Davalos Oscar A. http://orcid.org/0000-0002-9608-5701 Heydari A. Ali http://orcid.org/0000-0002-9141-3809 Fertig Elana J. http://orcid.org/0000-0003-3204-342X Sindi Suzanne S. http://orcid.org/0000-0003-2742-4332 Hoyer Katrina K. http://orcid.org/0000-0001-5443-0733 01 6 2023 2023.05.29.542760http://biorxiv.org/lookup/doi/10.1101/2023.05.29.542760 nihpp-2023.05.29.542760.pdf A limitation of current deep learning (DL) approaches for single-cell RNA sequencing (scRNAseq) analysis is the lack of interpretability. Moreover, existing pipelines are designed and trained for specific tasks used disjointly for different stages of analysis. We present scANNA, a novel interpretable DL model for scR-NAseq studies that leverages neural attention to learn gene associations. After training, the learned gene importance (interpretability) is used to perform downstream analyses (e.g., global marker selection and cell-type classification) without retraining. ScANNA’s performance is comparable to or better than state-of-the-art methods designed and trained for specific standard scRNAseq analyses even though scANNA was not trained for these tasks explicitly. ScANNA enables researchers to discover meaningful results without extensive prior knowledge or training separate task-specific models, saving time and enhancing scRNAseq analyses. ==== Body pmc