Deconvolution of Bulk Gene Expression Profiles with Single-Cell Transcriptomics to Develop a Cell Type Composition-Based Prognostic Model for Acute Myeloid Leukemia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34869351", "kind": "science-record", "revision": 4, "content_hash": "sha256:f3384fceca22ad489e50a646434ba7654fccc72c9480a688406857b0fe3f4178", "created_at": "2026-11-01T17:36:34Z", "updated_at": "2026-11-01T22:05:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Deconvolution of Bulk Gene Expression Profiles with Single-Cell Transcriptomics to Develop a Cell Type Composition-Based Prognostic Model for Acute Myeloid Leukemia.", "doi": "10.3389/fcell.2021.762260", "pmid": "34869351", "authors": ["Chengguqiu Dai", "Mengya Chen", "Chaolong Wang", "Xingjie Hao"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "Acute myeloid leukemia (AML) is one of the malignant hematologic cancers with rapid progress and poor prognosis. Most AML prognostic stratifications focused on genetic abnormalities. However, none of them was established based on the cell type compositions (CTCs) of peripheral blood or bone marrow aspirates from patients at diagnosis. Here we sought to develop a novel prognostic model for AML in adults based on the CTCs. First, we applied the CIBERSORT algorithm to estimate the CTCs for patients from two public datasets (GSE6891 and TCGA-LAML) using a custom gene expression signature reference constructed by an AML single-cell RNA sequencing dataset (GSE116256). Then, a CTC-based prognostic model was established using least absolute shrinkage and selection operator Cox regression, termed CTC score. The constructed prognostic model CTC score comprised 3 cell types, GMP-like, HSC-like, and T. Compared with the low-CTC-score group, the high-CTC-score group showed a 1.57-fold [95% confidence interval (CI), 1.23 to 2.00; p = 0.0002] and a 2.32-fold (95% CI, 1.53 to 3.51; p < 0.0001) higher overall mortality risk in the training set (GSE6891) and validation set (TCGA-LAML), respectively. When adjusting for age at diagnosis, cytogenetic risk, and karyotype, the CTC score remained statistically significant in both the training set [hazard ratio (HR) = 2.25; 95% CI, 1.20 to 4.24; p = 0.0119] and the validation set (HR = 7.97; 95% CI, 2.95 to 21.56; p < 0.0001]. We further compared the performance of the CTC score with two gene expression-based prognostic scores: the 17-gene leukemic stem cell score (LSC17 score) and the AML prognostic score (APS). It turned out that the CTC score achieved comparable performance at 1-, 2-, 3-, and 5-years timepoints and provided independent and additional prognostic information different from the LSC17 score and APS. In conclusion, the CTC score could serve as a powerful prognostic marker for AML and has great potential to assist clinicians to formulate individualized treatment plans.", "claims": [{"id": "claim-method", "statement": "With OS as the survival outcome, we performed the least absolute shrinkage and selection operator (LASSO) Cox regression (Simon et al., 2011) and 10-fold cross-validation using glmnet (version 4.1–1) R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34869351", "locator": "sections[9] \"Constructing an Acute Myeloid Leukemia Prognostic Model Based on Cell Type Compositions\" paragraph 3", "quote": "With OS as the survival outcome, we performed the least absolute shrinkage and selection operator (LASSO) Cox regression (Simon et al., 2011) and 10-fold cross-validation using glmnet (version 4.1–1) R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE116256, Gene Expression Ominibus, accession number:GSE116256; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE6891, Gene Expression Ominibus, accession number: GSE6891; https://portal.gdc.cancer.gov/, Genomic Data Commons Data Portal, TCGA-LAML; https://www.cbioportal.org/study/clinicalDataid=laml_tcga_pub, cBioPortal, Acute Myeloid Leukemia (TCGA, NEJM 2013).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34869351", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE116256, Gene Expression Ominibus, accession number:GSE116256; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE6891, Gene Expression Ominibus, accession number: GSE6891; https://portal.gdc.cancer.gov/, Genomic Data Commons Data Portal, TCGA-LAML; https://www.cbioportal.org/study/clinicalDataid=laml_tcga_pub, cBioPortal, Acute Myeloid Leukemia (TCGA, NEJM 2013)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Compared with the low-CTC-score group, the high-CTC-score group showed a 1.57-fold [95% confidence interval (CI), 1.23 to 2.00; p = 0.0002] and a 2.32-fold (95% CI, 1.53 to 3.51; p < 0.0001) higher overall mortality risk in the training set (GSE6891) and validation set (TCGA-LAML), respectively.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Compared with the low-CTC-score group, the high-CTC-score group showed a 1.57-fold [95% confidence interval (CI), 1.23 to 2.00; p = 0.0002] and a 2.32-fold (95% CI, 1.53 to 3.51; p < 0.0001) higher overall mortality risk in the training set (GSE6891) and validation set (TCGA-LAML), respectively."}, "evidence": [{"asset": "source:pmid:34869351", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Compared with the low-CTC-score group, the high-CTC-score group showed a 1.57-fold [95% confidence interval (CI), 1.23 to 2.00; p = 0.0002] and a 2.32-fold (95% CI, 1.53 to 3.51; p < 0.0001) higher overall mortality risk in the training set (GSE6891) and validation set (TCGA-LAML), respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Compared with the low-CTC-score group, the high-CTC-score group showed a 1.57-fold [95% confidence interval (CI), 1.23 to 2.00; p = 0.0002] and a 2.32-fold (95% CI, 1.53 to 3.51; p < 0.0001) higher overall mortality risk in the training set (GSE6891) and validation set (TCGA-LAML), respectively.", "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:34869351"], "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:GSE116256"], "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:GSE116256"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34869351", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2021.762260", "sha256": "sha256:550d204b2f7a03ec8ce5b4d430da97e5f491640d89160fe0ee761b3e5065cde3", "bytes": 46497, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcell.2021.762260", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8633313", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE116256", "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=GSE116256", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE116256", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE116256, Gene Expression Ominibus, accession number:GSE116256; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE6891, Gene Expression Ominibus, accession number: GSE6891; https://portal.gdc.cancer.gov/, Genomic Data Commons Data Portal, TCGA-LAML; https://www.cbioportal.org/study/clinicalDataid=laml_tcga_pub, cBioPortal, Acute Myeloid Leukemia (TCGA, NEJM 2013).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE116256, Gene Expression Ominibus, accession number:GSE116256; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE6891, Gene Expression Ominibus, accession number: GSE6891; https://portal.gdc.cancer.gov/, Genomic Data Commons Data Portal, TCGA-LAML; https://www.cbioportal.org/study/clinicalDataid=laml_tcga_pub, cBioPortal, Acute Myeloid Leukemia (TCGA, NEJM 2013).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3587923", "GSM3587924", "GSM3587925", "GSM3587926", "GSM3587927", "GSM3587928", "GSM3587929", "GSM3587930", "GSM3587931", "GSM3587932", "GSM3587933", "GSM3587934", "GSM3587935", "GSM3587936", "GSM3587937", "GSM3587938", "GSM3587939", "GSM3587940", "GSM3587941", "GSM3587942", "GSM3587943", "GSM3587944", "GSM3587945", "GSM3587946", "GSM3587947", "GSM3587948", "GSM3587949", "GSM3587950", "GSM3587951", "GSM3587952", "GSM3587953", "GSM3587954", "GSM3587955", "GSM3587956", "GSM3587957", "GSM3587958", "GSM3587959", "GSM3587960", "GSM3587961", "GSM3587962", "GSM3587963", "GSM3587964", "GSM3587965", "GSM3587966", "GSM3587967", "GSM3587968", "GSM3587969", "GSM3587970", "GSM3587971", "GSM3587972", "GSM3587973", "GSM3587974", "GSM3587975", "GSM3587976", "GSM3587977", "GSM3587978", "GSM3587979", "GSM3587980", "GSM3587981", "GSM3587982", "GSM3587983", "GSM3587984", "GSM3587985", "GSM3587986", "GSM3587987", "GSM3587988", "GSM3587989", "GSM3587990", "GSM3587991", "GSM3587992", "GSM3587993", "GSM3587994", "GSM3587995", "GSM3587996", "GSM3587997", "GSM3587998", "GSM3587999", "GSM3588000", "GSM3588001", "GSM3588002", "GSM3588003", "GSM3588004", "GSM3588005"], "sample_count": 83, "group_sizes": null, "group_sizes_basis": null, "platform": "24106;18573", "taxon": "Homo sapiens", "title": "Single-cell RNA-seq reveals AML hierarchies relevant to disease progression and immunity", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE6891", "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=GSE6891", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE6891", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE116256, Gene Expression Ominibus, accession number:GSE116256; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE6891, Gene Expression Ominibus, accession number: GSE6891; https://portal.gdc.cancer.gov/, Genomic Data Commons Data Portal, TCGA-LAML; https://www.cbioportal.org/study/clinicalDataid=laml_tcga_pub, cBioPortal, Acute Myeloid Leukemia (TCGA, NEJM 2013).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE116256, Gene Expression Ominibus, accession number:GSE116256; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE6891, Gene Expression Ominibus, accession number: GSE6891; https://portal.gdc.cancer.gov/, Genomic Data Commons Data Portal, TCGA-LAML; https://www.cbioportal.org/study/clinicalDataid=laml_tcga_pub, cBioPortal, Acute Myeloid Leukemia (TCGA, NEJM 2013).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM158711", "GSM158712", "GSM158713", "GSM158714", "GSM158715", "GSM158716", "GSM158717", "GSM158718", "GSM158719", "GSM158720", "GSM158721", "GSM158722", "GSM158723", "GSM158724", "GSM158725", "GSM158726", "GSM158727", "GSM158728", "GSM158729", "GSM158730", "GSM158731", "GSM158732", "GSM158733", "GSM158734", "GSM158735", "GSM158736", "GSM158737", "GSM158738", "GSM158739", "GSM158740", "GSM158741", "GSM158742", "GSM158743", "GSM158744", "GSM158745", "GSM158746", 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