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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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SD2: spatially resolved transcriptomics deconvolution through integration of dropout and spatial information.
doi
10.1093/bioinformatics/btac605
pmid
36063455
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Haoyang Li
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Hanmin Li
[2]
Juexiao Zhou
[3]
Xin Gao
journal
Bioinformatics (Oxford, England)
year
2022
abstract
MOTIVATION: Unveiling the heterogeneity in the tissues is crucial to explore cell-cell interactions and cellular targets of human diseases. 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. RESULTS: 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. AVAILABILITY AND IMPLEMENTATION: The SD2 is freely available in github (https://github.com/leihouyeung/SD2) and Zenodo (https://doi.org/10.5281/zenodo.7024684). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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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).
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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).
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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.
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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.
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SD2 outperformed SPOTLight, DSTG, and cell2location on the simulated seqFISH+ benchmark, achieving an RMSE of 0.06 and a JSD of 0.21.
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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).
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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).
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SD2 outperformed SPOTLight, DSTG, and cell2location on the simulated seqFISH+ benchmark, achieving an RMSE of 0.06 and a JSD of 0.21.
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ba34b49490d9bfaf
lineage object · 4 fields
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pmid:36063455
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sha256:c99305879c59e328e1e4d3b31e27e66f802ab444d6ac187ec085508acb4d1e4c
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null
gaps array · 13 items
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asset:data:geo:GSE111672 licence not read
[1]
asset:data:geo:GSE111672 not downloaded
[2]
asset:data:geo:GSE157079 licence not read
[3]
asset:data:geo:GSE157079 not downloaded
[4]
asset:data:geo:GSE6036 licence not read
[5]
asset:data:geo:GSE6036 not downloaded
[6]
asset:data:geo:GSE98674 licence not read
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asset:data:geo:GSE98674 not downloaded
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method.reader_named_unmapped
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review.machine_critique
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99e1195c7d6f
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support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 3 items
[0]
SD2: spatially resolved transcriptomics deconvolution through integration of dropout
[1]
cellular targets of human diseases. Spatial transcriptomics (ST) supplies spatial gene expression profil
[2]
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
[1] object · 11 fields
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data_generation
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scrna_seq
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99e1195c7d6f
required_operations array · 0 items
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unsupported
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 4 items
[0]
raditionally considered as an obstruction in single-cell RNA sequencing data (scRNA-seq) analysis. First, we extract
[1]
truction in single-cell RNA sequencing data (scRNA-seq) analysis. First, we extract the dropout-bas
[2]
ed genes as informative features from ST and scRNA-seq data by fitting a Michaelis-Menten function.
[3]
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
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36063455", "kind": "science-record", "revision": 8, "content_hash": "sha256:92a6a4efe45cf81e890453987384d077580ca835389f77d0981cdd0a5e78c2a7", "created_at": "2026-11-01T18:15:16Z", "updated_at": "2026-11-01T23:48:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "SD2: spatially resolved transcriptomics deconvolution through integration of dropout and spatial information.", "doi": "10.1093/bioinformatics/btac605", "pmid": "36063455", "authors": ["Haoyang Li", "Hanmin Li", "Juexiao Zhou", "Xin Gao"], "journal": "Bioinformatics (Oxford, England)", "year": 2022, "abstract": "MOTIVATION: Unveiling the heterogeneity in the tissues is crucial to explore cell-cell interactions and cellular targets of human diseases. 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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE111672"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE111672"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36063455", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1093/bioinformatics/btac605", "sha256": "sha256:ada04be3a74dcb50ee6ffe70b9c4d5ba7a908266817be89b0c66289c0a52ca39", "bytes": 33627, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1093/bioinformatics/btac605", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9789790", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE111672", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111672", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE111672", "version": null, "note": "The seqFISH+ dataset is collected from GSE98674 and corresponded scRNA-seq dataset is collected from GSE6036. 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