9 research outputs found

    DestVI identifies continuums of cell types in spatial transcriptomics data

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    Most spatial transcriptomics technologies are limited by their resolution, with spot sizes larger than that of a single cell. Although joint analysis with single-cell RNA sequencing can alleviate this problem, current methods are limited to assessing discrete cell types, revealing the proportion of cell types inside each spot. To identify continuous variation of the transcriptome within cells of the same type, we developed Deconvolution of Spatial Transcriptomics profiles using Variational Inference (DestVI). Using simulations, we demonstrate that DestVI outperforms existing methods for estimating gene expression for every cell type inside every spot. Applied to a study of infected lymph nodes and of a mouse tumor model, DestVI provides high-resolution, accurate spatial characterization of the cellular organization of these tissues and identifies cell-type-specific changes in gene expression between different tissue regions or between conditions. DestVI is available as part of the open-source software package scvi-tools ( https://scvi-tools.org )

    Predicting cellular responses to complex perturbations in high‐throughput screens

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    Abstract Recent advances in multiplexed single‐cell transcriptomics experiments facilitate the high‐throughput study of drug and genetic perturbations. However, an exhaustive exploration of the combinatorial perturbation space is experimentally unfeasible. Therefore, computational methods are needed to predict, interpret, and prioritize perturbations. Here, we present the compositional perturbation autoencoder (CPA), which combines the interpretability of linear models with the flexibility of deep‐learning approaches for single‐cell response modeling. CPA learns to in silico predict transcriptional perturbation response at the single‐cell level for unseen dosages, cell types, time points, and species. Using newly generated single‐cell drug combination data, we validate that CPA can predict unseen drug combinations while outperforming baseline models. Additionally, the architecture's modularity enables incorporating the chemical representation of the drugs, allowing the prediction of cellular response to completely unseen drugs. Furthermore, CPA is also applicable to genetic combinatorial screens. We demonstrate this by imputing in silico 5,329 missing combinations (97.6% of all possibilities) in a single‐cell Perturb‐seq experiment with diverse genetic interactions. We envision CPA will facilitate efficient experimental design and hypothesis generation by enabling in silico response prediction at the single‐cell level and thus accelerate therapeutic applications using single‐cell technologies

    Predicting cellular responses to complex perturbations in high‐throughput screens

    No full text
    Recent advances in multiplexed single-cell transcriptomics experiments facilitate the high-throughput study of drug and genetic perturbations. However, an exhaustive exploration of the combinatorial perturbation space is experimentally unfeasible. Therefore, computational methods are needed to predict, interpret, and prioritize perturbations. Here, we present the compositional perturbation autoencoder (CPA), which combines the interpretability of linear models with the flexibility of deep-learning approaches for single-cell response modeling. CPA learns to in silico predict transcriptional perturbation response at the single-cell level for unseen dosages, cell types, time points, and species. Using newly generated single-cell drug combination data, we validate that CPA can predict unseen drug combinations while outperforming baseline models. Additionally, the architecture's modularity enables incorporating the chemical representation of the drugs, allowing the prediction of cellular response to completely unseen drugs. Furthermore, CPA is also applicable to genetic combinatorial screens. We demonstrate this by imputing in silico 5,329 missing combinations (97.6% of all possibilities) in a single-cell Perturb-seq experiment with diverse genetic interactions. We envision CPA will facilitate efficient experimental design and hypothesis generation by enabling in silico response prediction at the single-cell level and thus accelerate therapeutic applications using single-cell technologies

    scverse/scvi-tools: scvi-tools 1.1.0-rc.1

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    <p>See the <a href="https://docs.scvi-tools.org/en/stable/release_notes/index.html">release notes</a> for all changes.</p> <p>This release is available via PyPi:</p> <pre><code>pip install scvi-tools </code></pre> <p>Conda availability will follow (< 2 days typically)</p> <p>Please report any issues on <a href="https://github.com/scverse/scvi-tools">GitHub</a>.</p&gt

    scverse/scvi-tools: scvi-tools 1.1.0-rc.2

    No full text
    <p>See the <a href="https://docs.scvi-tools.org/en/stable/release_notes/index.html">release notes</a> for all changes.</p> <p>This release is available via PyPi:</p> <pre><code>pip install scvi-tools </code></pre> <p>Conda availability will follow (< 2 days typically)</p> <p>Please report any issues on <a href="https://github.com/scverse/scvi-tools">GitHub</a>.</p&gt

    scverse/scvi-tools: scvi-tools 1.1.0-rc.2

    No full text
    <p>See the <a href="https://docs.scvi-tools.org/en/stable/release_notes/index.html">release notes</a> for all changes.</p> <p>This release is available via PyPi:</p> <pre><code>pip install scvi-tools </code></pre> <p>Conda availability will follow (< 2 days typically)</p> <p>Please report any issues on <a href="https://github.com/scverse/scvi-tools">GitHub</a>.</p&gt

    scverse/scvi-tools: scvi-tools 1.1.0-rc.2

    No full text
    <p>See the <a href="https://docs.scvi-tools.org/en/stable/release_notes/index.html">release notes</a> for all changes.</p> <p>This release is available via PyPi:</p> <pre><code>pip install scvi-tools </code></pre> <p>Conda availability will follow (< 2 days typically)</p> <p>Please report any issues on <a href="https://github.com/scverse/scvi-tools">GitHub</a>.</p&gt
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