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pmid:36063455
SD2: spatially resolved transcriptomics deconvolution through integration of dropout and spatial information.
Haoyang Li · Hanmin Li · Juexiao Zhou · Xin Gao
Bioinformatics (Oxford, England) · 2022 doi:10.1093/bioinformatics/btac605
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Complete file
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Spatial transcriptomics (ST) supplies spatial gene expression profile which has revolutionized our biological understanding, but variations in cell-type proportions of each spot with dozens of cells would confound downstream analysis. Therefore, deconvolution of ST has been an indispensable step and a technical challenge toward the higher-resolution panorama of tissues.\nRESULTS: Here, we propose a novel ST deconvolution method called SD2 integrating spatial information of ST data and embracing an important characteristic, dropout, which is traditionally considered as an obstruction in single-cell RNA sequencing data (scRNA-seq) analysis. First, we extract the dropout-based genes as informative features from ST and scRNA-seq data by fitting a Michaelis-Menten function. After synthesizing pseudo-ST spots by randomly composing cells from scRNA-seq data, auto-encoder is applied to discover low-dimensional and non-linear representation of the real- and pseudo-ST spots. Next, we create a graph containing embedded profiles as nodes, and edges determined by transcriptional similarity and spatial relationship. Given the graph, a graph convolutional neural network is used to predict the cell-type compositions for real-ST spots. We benchmark the performance of SD2 on the simulated seqFISH+ dataset with different resolutions and measurements which show superior performance compared with the state-of-the-art methods. SD2 is further validated on three real-world datasets with different ST technologies and demonstrates the capability to localize cell-type composition accurately with quantitative evidence. Finally, ablation study is conducted to verify the contribution of different modules proposed in SD2.\nAVAILABILITY AND IMPLEMENTATION: The SD2 is freely available in github (https://github.com/leihouyeung/SD2) and Zenodo (https://doi.org/10.5281/zenodo.7024684).\nSUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "claims": [{"id": "claim-method", "statement": "Through the comparison with ground truth, we observed that SD2 outperformed the other three methods in root mean square error (RMSE) and Jensen–Shannon Divergence (JSD).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36063455", "locator": "sections[8] \"3.2 Benchmark evaluation\" paragraph 5", "quote": "Through the comparison with ground truth, we observed that SD2 outperformed the other three methods in root mean square error (RMSE) and Jensen–Shannon Divergence (JSD)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The seqFISH+ dataset is collected from GSE98674 and corresponded scRNA-seq dataset is collected from GSE6036. The MERFISH datasets are collected from https://datadryad.org/stash/dataset/doi:10.5061/dryad.8t8s248/ and scRNA-seq data is from https://github.com/rdong08/spatialDWLS_dataset/tree/main/datasets. ST and scRNA-seq data from PDAC are collected from GSE111672. ST data from adult mouse brain are collected from 10X Genomics and the corresponding scRNA-seq data are collected from allen institute which are sequenced by smart-seq. The ST data of mouse kidney are collected from 10X Genomics and scRNA-seq data are from GSE157079.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36063455", "locator": "sections[14] \"Data Availability\" paragraph 2", "quote": "The seqFISH+ dataset is collected from GSE98674 and corresponded scRNA-seq dataset is collected from GSE6036. The MERFISH datasets are collected from https://datadryad.org/stash/dataset/doi:10.5061/dryad.8t8s248/ and scRNA-seq data is from https://github.com/rdong08/spatialDWLS_dataset/tree/main/datasets. ST and scRNA-seq data from PDAC are collected from GSE111672. ST data from adult mouse brain are collected from 10X Genomics and the corresponding scRNA-seq data are collected from allen institute which are sequenced by smart-seq. The ST data of mouse kidney are collected from 10X Genomics and scRNA-seq data are from GSE157079."}], "state": "complete"}, {"id": "claim-target-result", "statement": "SD2 outperformed SPOTLight, DSTG, and cell2location on the simulated seqFISH+ benchmark, achieving an RMSE of 0.06 and a JSD of 0.21.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36063455", "locator": "sections[8] \"3.2 Benchmark evaluation\" paragraph 5", "quote": "Through the comparison with ground truth, we observed that SD2 outperformed the other three methods in root mean square error (RMSE) and Jensen–Shannon Divergence (JSD)."}, {"asset": "source:pmid:36063455", "locator": "sections[8] \"3.2 Benchmark evaluation\" paragraph 5", "quote": "In particular, SD2 has RMSE of 0.06 and JSD of 0.21 which shows the most similar pattern compared with ground truth (Fig. 2A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "SD2 outperformed SPOTLight, DSTG, and cell2location on the simulated seqFISH+ benchmark, achieving an RMSE of 0.06 and a JSD of 0.21.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36063455"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Spatial transcriptomics (ST) supplies spatial gene expression profil", "considered as an obstruction in single-cell RNA sequencing data (scRNA-seq) analysis. First, we extract"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["raditionally considered as an obstruction in single-cell RNA sequencing data (scRNA-seq) analysis. First, we extract", "truction in single-cell RNA sequencing data (scRNA-seq) analysis. First, we extract the dropout-bas", "ed genes as informative features from ST and scRNA-seq data by fitting a Michaelis-Menten function.", "do-ST spots by randomly composing cells from scRNA-seq data, auto-encoder is applied to discover lo"], "order_basis": "paper_text_order:797", "id": "assay:2"}]}