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      BANKSY unifies cell typing and tissue domain segmentation for scalable spatial omics data analysis

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          Abstract

          Spatial omics data are clustered to define both cell types and tissue domains. We present Building Aggregates with a Neighborhood Kernel and Spatial Yardstick (BANKSY), an algorithm that unifies these two spatial clustering problems by embedding cells in a product space of their own and the local neighborhood transcriptome, representing cell state and microenvironment, respectively. BANKSY’s spatial feature augmentation strategy improved performance on both tasks when tested on diverse RNA (imaging, sequencing) and protein (imaging) datasets. BANKSY revealed unexpected niche-dependent cell states in the mouse brain and outperformed competing methods on domain segmentation and cell typing benchmarks. BANKSY can also be used for quality control of spatial transcriptomics data and for spatially aware batch effect correction. Importantly, it is substantially faster and more scalable than existing methods, enabling the processing of millions of cell datasets. In summary, BANKSY provides an accurate, biologically motivated, scalable and versatile framework for analyzing spatially resolved omics data.

          Abstract

          BANKSY is an algorithm with R and Python implementations that identifies both cell types and tissue domains from spatially resolved omics data by incorporating spatial kernels capturing microenvironmental information. It is applicable to a range of technologies and is scalable to millions of cells.

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          SciPy 1.0: fundamental algorithms for scientific computing in Python

          SciPy is an open-source scientific computing library for the Python programming language. Since its initial release in 2001, SciPy has become a de facto standard for leveraging scientific algorithms in Python, with over 600 unique code contributors, thousands of dependent packages, over 100,000 dependent repositories and millions of downloads per year. In this work, we provide an overview of the capabilities and development practices of SciPy 1.0 and highlight some recent technical developments.
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            Comprehensive Integration of Single-Cell Data

            Single-cell transcriptomics has transformed our ability to characterize cell states, but deep biological understanding requires more than a taxonomic listing of clusters. As new methods arise to measure distinct cellular modalities, a key analytical challenge is to integrate these datasets to better understand cellular identity and function. Here, we develop a strategy to "anchor" diverse datasets together, enabling us to integrate single-cell measurements not only across scRNA-seq technologies, but also across different modalities. After demonstrating improvement over existing methods for integrating scRNA-seq data, we anchor scRNA-seq experiments with scATAC-seq to explore chromatin differences in closely related interneuron subsets and project protein expression measurements onto a bone marrow atlas to characterize lymphocyte populations. Lastly, we harmonize in situ gene expression and scRNA-seq datasets, allowing transcriptome-wide imputation of spatial gene expression patterns. Our work presents a strategy for the assembly of harmonized references and transfer of information across datasets.
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              Integrated analysis of multimodal single-cell data

              Summary The simultaneous measurement of multiple modalities represents an exciting frontier for single-cell genomics and necessitates computational methods that can define cellular states based on multimodal data. Here, we introduce “weighted-nearest neighbor” analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of 211,000 human peripheral blood mononuclear cells (PBMCs) with panels extending to 228 antibodies to construct a multimodal reference atlas of the circulating immune system. Multimodal analysis substantially improves our ability to resolve cell states, allowing us to identify and validate previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets and to interpret immune responses to vaccination and coronavirus disease 2019 (COVID-19). Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets and to look beyond the transcriptome toward a unified and multimodal definition of cellular identity.
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                Author and article information

                Contributors
                chenkh@gis.a-star.edu.sg
                prabhakars@gis.a-star.edu.sg
                Journal
                Nat Genet
                Nat Genet
                Nature Genetics
                Nature Publishing Group US (New York )
                1061-4036
                1546-1718
                27 February 2024
                27 February 2024
                2024
                : 56
                : 3
                : 431-441
                Affiliations
                [1 ]Spatial and Single Cell Systems Domain, Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), ( https://ror.org/05k8wg936) Singapore, Republic of Singapore
                [2 ]Faculty of Science, National University of Singapore, ( https://ror.org/01tgyzw49) Singapore, Republic of Singapore
                [3 ]Department of Chemical and Biomolecular Engineering, National University of Singapore, ( https://ror.org/01tgyzw49) Singapore, Republic of Singapore
                [4 ]Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), ( https://ror.org/044w3nw43) Singapore, Republic of Singapore
                [5 ]Veranome Biosystems, Mountain View, CA USA
                [6 ]School of Computing, National University of Singapore, ( https://ror.org/01tgyzw49) Singapore, Republic of Singapore
                [7 ]Singapore Eye Research Institute, ( https://ror.org/02crz6e12) Singapore, Republic of Singapore
                [8 ]International Research Laboratory on Artificial Intelligence, Singapore, Republic of Singapore
                [9 ]School of Biological Sciences, Nanyang Technological University, ( https://ror.org/02e7b5302) Singapore, Republic of Singapore
                [10 ]Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, ( https://ror.org/015p9va32) Singapore, Republic of Singapore
                [11 ]Population and Global Health, Lee Kong Chian School of Medicine, Nanyang Technological University, ( https://ror.org/02e7b5302) Singapore, Republic of Singapore
                [12 ]Cancer Science Institute of Singapore, National University of Singapore, ( https://ror.org/01tgyzw49) Singapore, Republic of Singapore
                Author information
                http://orcid.org/0000-0003-1670-1824
                http://orcid.org/0000-0002-6280-7729
                http://orcid.org/0000-0002-4983-4714
                http://orcid.org/0000-0003-2094-6365
                http://orcid.org/0000-0002-4851-484X
                http://orcid.org/0000-0002-7104-9931
                http://orcid.org/0000-0001-7406-7919
                http://orcid.org/0000-0002-6409-0661
                Article
                1664
                10.1038/s41588-024-01664-3
                10937399
                38413725
                2d4e89e4-a85f-4baa-8d1f-49c91b5fe753
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 April 2023
                : 16 January 2024
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001349, MOH | National Medical Research Council (NMRC);
                Award ID: OFIRG21jun-0090
                Award ID: OF-YIRG18nov-0014
                Award ID: OFIRG-000618-00
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100001348, Agency for Science, Technology and Research (A*STAR);
                Award ID: #H18/01/a0/020
                Award ID: 202D800010
                Award ID: 202D800010
                Award ID: H18/01/a0/020
                Award ID: H18/01/a0/020
                Award ID: I1801E0029
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100001381, National Research Foundation Singapore (National Research Foundation-Prime Minister’s office, Republic of Singapore);
                Award ID: NRF-CRP25-2020-0001
                Award Recipient :
                Categories
                Article
                Custom metadata
                © Springer Nature America, Inc. 2024

                Genetics
                software,data processing,gene expression,bioinformatics
                Genetics
                software, data processing, gene expression, bioinformatics

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