Proteomic Studies for the Investigation of γ-Globin Induction by Decitabine in Human Primary Erythroid Progenitor Cultures.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31947809", "kind": "science-record", "revision": 6, "content_hash": "sha256:69234fb12b1759c85fba7c01702afa4ef8092a61164847c24a85139a800fe79b", "created_at": "2026-11-01T15:40:55Z", "updated_at": "2026-11-01T21:22:49Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Proteomic Studies for the Investigation of γ-Globin Induction by Decitabine in Human Primary Erythroid Progenitor Cultures.", "doi": "10.3390/jcm9010134", "pmid": "31947809", "authors": ["Andria Theodorou", "Marios Phylactides", "Eleni Katsantoni", "Kostas Vougas", "Spyros D Garbis", "Pavlos Fanis", "Maria Sitarou", "Swee Lay Thein", "Marina Kleanthous"], "journal": "Journal of clinical medicine", "year": 2020, "abstract": "Reactivation of γ-globin is considered a promising approach for the treatment of β-thalassemia and sickle cell disease. Therapeutic induction of γ-globin expression, however, is fraught with lack of suitable therapeutic targets. The aim of this study was to investigate the effects that treatment with decitabine has on the proteome of human primary erythroid cells from healthy and thalassemic volunteers, as a means of identifying new potential pharmacological targets. Decitabine is a known γ-globin inducer, which is not, however, safe enough for clinical use. A proteomic approach utilizing isobaric tags for relative and absolute quantitation (iTRAQ) analysis, in combination with high-pH reverse phase peptide fractionation followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), was employed to investigate the effects of decitabine treatment. Bioinformatics analysis making use of the Database for Annotation, Visualization and Integrated Discovery (DAVID) was employed for functional annotation of the 192 differentially expressed proteins identified. The data are available via ProteomeXchange with identifier PXD006889. The proteins fall into various biological pathways, such as the NF-κB signaling pathway, and into many functional categories including regulation of cell proliferation, transcription factor and DNA binding, protein stabilization, chromatin modification and organization, and oxidative stress proteins.", "claims": [{"id": "claim-method", "statement": "Log transformation of iTRAQ ratios resulted in normal distribution as checked by Kolmogorov-Smirnof test for normality.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31947809", "locator": "sections[10] \"2.5. 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The effect of decitabine on the levels of fetal hemoglobin levels in primary human erythroid progenitor cells from healthy and thalassemic donors. Fetal hemoglobin (HbF) levels were determined after 6 days of treatment with decitabine (Dec). The results are the average of 12 healthy cultures and 11 thalassemic cultures.", "structure": {"pmcid": "PMC7019605", "section_index": 12, "section_title": "3.1. Decitabine Increases HbF in Primary Erythroid Cultures from Healthy Donors and Thalassemic Patients", "row_count": 3, "column_count": 3}, "table": {"label": "Table 1", "caption": "The effect of decitabine induction on human erythroid progenitor cell cultures. The effect of decitabine on the levels of fetal hemoglobin levels in primary human erythroid progenitor cells from healthy and thalassemic donors. Fetal hemoglobin (HbF) levels were determined after 6 days of treatment with decitabine (Dec). The results are the average of 12 healthy cultures and 11 thalassemic cultures.", "rows": [["Samples", "HbF Levels (% Relative to Un-Treated Control)", "p-Value (Paired t-Test ± Dec)"], ["Healthy", "62.68 ± 28.66", "0.00003"], ["Thalassemic", "43.89 ± 38.72", "0.0027"]], "row_count": 3, "column_count": 3, "numeric_cells": 4, "header_rows": 1, "locator": "section[12]/table-wrap[1]#jcm-09-00134-t001"}}, {"id": "asset:table:pmid:31947809:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:98becebfff38d0946f0e4f709651e41739237ba74c87f54e6d52985fdd685570", "bytes": 1190, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#jcm-09-00134-t002", "version": null, "note": "HbF induction data for the primary erythroid cultures from healthy and thalassemic donors selected for proteomic analysis. For each culture, the HbF levels before treatment with decitabine (un-treated) and after six days of treatment with decitabine are shown. (A) Data for cultures from healthy controls and (B) form thalassemic patients.", "structure": {"pmcid": "PMC7019605", "section_index": 13, "section_title": "3.2. Proteomic Analysis of Primary Human Erythroid Cultures Revealed 192 Proteins that Are Significantly Differentially Expressed Following Treatment with Decitabine", "row_count": 22, "column_count": 4}, "table": {"label": "Table 2", "caption": "HbF induction data for the primary erythroid cultures from healthy and thalassemic donors selected for proteomic analysis. For each culture, the HbF levels before treatment with decitabine (un-treated) and after six days of treatment with decitabine are shown. (A) Data for cultures from healthy controls and (B) form thalassemic patients.", "rows": [["(A)"], ["Healthy Samples"], ["Culture ID", "HbF (%)", "Increase in HbF (% Relative to Un-Treated)"], ["Un-treated", "300 nM Dec"], ["H1", "3.74", "8.01", "114.2"], ["H2", "10.3", "19.65", "90.89"], ["H3", "5.65", "8.86", "56.83"], ["H4", "12.83", "19.73", "53.78"], ["H5", "5.07", "9.1", "79.51"], ["H6", "2.53", "4.22", "66.78"], ["Average", "6.69", "11.6", "77"], ["(B)"], ["Thalassemic Samples"], ["Culture ID", "HbF (%)", "Increase in HbF (% Relative to Un-Treated)"], ["Un-Treated", "300 nM Dec"], ["Th1", "21.79", "31.35", "43.88"], ["Th2", "15.8", "22.65", "43.35"], ["Th3", "18.11", "45.21", "149.68"], ["Th4", "23.48", "36.67", "56.13"], ["Th5", "9.87", "15.46", "56.64"], ["Th6", "17.61", "27", "53.29"], ["Average", "17.78", "29.72", "67.16"]], "row_count": 22, "column_count": 4, "numeric_cells": 44, "header_rows": 0, "locator": "section[13]/table-wrap[1]#jcm-09-00134-t002"}}, {"id": "asset:table:pmid:31947809:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1b2650ad242c4e6ecbe2845ddab8e1fe9963d88af61205cc43f2f224dfcceff2", "bytes": 1042, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#jcm-09-00134-t003", "version": null, "note": "Numbers of significantly differentially expressed proteins. The number of statistically significant differentially expressed proteins identified through comparison of the different culture conditions (treated healthy cultures versus un-treated healthy cultures (ratio 1), treated thalassemic cultures versus un-treated thalassemic cultures (ratio 2)). Expression ratios represent the fold change in protein expression.", "structure": {"pmcid": "PMC7019605", "section_index": 13, "section_title": "3.2. Proteomic Analysis of Primary Human Erythroid Cultures Revealed 192 Proteins that Are Significantly Differentially Expressed Following Treatment with Decitabine", "row_count": 4, "column_count": 9}, "table": {"label": "Table 3", "caption": "Numbers of significantly differentially expressed proteins. The number of statistically significant differentially expressed proteins identified through comparison of the different culture conditions (treated healthy cultures versus un-treated healthy cultures (ratio 1), treated thalassemic cultures versus un-treated thalassemic cultures (ratio 2)). Expression ratios represent the fold change in protein expression.", "rows": [["", "Number of Proteins with p-Value < 0.05", "Up-Regulated Proteins", "Down-Regulated Proteins"], ["Number of Proteins", "% Proteins with Expression Ratio < 1.2", "1.2 < % Proteins with Expression Ratio > 2", "% Proteins with Expression Ratio > 2", "Number of Proteins", "% Proteins with Expression Ratio < 0.8", "% Proteins with Expression Ratio < 0.5"], ["Ratio1", "105", "47", "0", "95.7", "4.3", "58", "100", "0"], ["Ratio2", "110", "55", "65.5", "25.5", "9.1", "55", "92.7", "7.2"]], "row_count": 4, "column_count": 9, "numeric_cells": 22, "header_rows": 2, "locator": "section[13]/table-wrap[2]#jcm-09-00134-t003"}}, {"id": "asset:table:pmid:31947809:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:dfb0c346e4b35c7aff36890d5ad581b1c6f45cf890c9f72b91a4176ec2e9bded", "bytes": 2661, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[3]#jcm-09-00134-t004", "version": null, "note": "Functional analysis of the differentially expressed proteins using Database for Annotation, Visualization and Integrated Discovery (DAVID). Bioinformatic analysis of the 105 significantly differentially expressed proteins in response to decitabine in human primary erythroid cultures from healthy donors (Ratio 1) and the 110 significantly differentially expressed proteins in response to decitabine in human primary erythroid cultures from thalassemic donors (Ratio 2). Functional analysis by DAVID of significantly differentially expressed proteins (ratios with p-value < 0.05) using as a reference list of all 2189 proteins identified, grouped proteins according to their biological process (BP), molecular function (MF), and cellular component (CC). In DAVID, protein groups are categorized according to their enrichment scores and corresponding p-value and Benjamini values.", "structure": {"pmcid": "PMC7019605", "section_index": 13, "section_title": "3.2. Proteomic Analysis of Primary Human Erythroid Cultures Revealed 192 Proteins that Are Significantly Differentially Expressed Following Treatment with Decitabine", "row_count": 25, "column_count": 6}, "table": {"label": "Table 4", "caption": "Functional analysis of the differentially expressed proteins using Database for Annotation, Visualization and Integrated Discovery (DAVID). Bioinformatic analysis of the 105 significantly differentially expressed proteins in response to decitabine in human primary erythroid cultures from healthy donors (Ratio 1) and the 110 significantly differentially expressed proteins in response to decitabine in human primary erythroid cultures from thalassemic donors (Ratio 2). Functional analysis by DAVID of significantly differentially expressed proteins (ratios with p-value < 0.05) using as a reference list of all 2189 proteins identified, grouped proteins according to their biological process (BP), molecular function (MF), and cellular component (CC). In DAVID, protein groups are categorized according to their enrichment scores and corresponding p-value and Benjamini values.", "rows": [["", "Functional Clustering", "Enrichment Score", "Count", "p-Value", "Benjamini"], ["Ratio 1", "", "", "", "", ""], ["Transcription factor binding", "MF", "1.56", "11", "0.0045", "0.75"], ["Regulation of cell growth", "BP", "1.4", "5", "0.0081", "0.94"], ["Regulation of cellular component size", "BP", "1.4", "7", "0.015", "0.89"], ["Regulation of protein localization", "BP", "1.32", "5", "0.012", "0.88"], ["Lipid transport", "BP", "1.32", "6", "0.0027", "0.94"], ["Focal adhesion", "CC", "1.13", "5", "0.02", "0.74"], ["Kinase inhibitor activity", "MF", "0.89", "3", "0.068", "0.91"], ["Protein stabilization", "BP", "0.92", "4", "0.0092", "0.91"], ["Protein kinase cascade", "BP", "0.79", "6", "0.035", "0.98"], ["Chromatin organization", "BP", "0.74", "8", "0.047", "0.96"], ["Transcription cofactor activation", "MF", "0.72", "8", "0.012", "0.83"], ["Macromolecular complex assembly", "BP", "0.7", "15", "0.038", "0.97"], ["Regulation of I-kappaB kinase/NF-kappaB cascade", "BP", "0.66", "4", "0.055", "0.97"], ["Regulation of transferase activity", "BP", "0.61", "6", "0.039", "0.96"], ["Ratio 2", "", "", "", "", ""], ["Transition metal ion binding", "MF", "1.52", "19", "1.70 × 102", "9.90 × 101"], ["Zing finger", "MF", "1.52", "10", "2.00 × 102", "9.80 × 101"], ["Cerebral cortex development", "BP", "1.35", "3", "2.50 × 102", "9.80 × 101"], ["Chromatin organization", "BP", "1.35", "12", "2.00 × 104", "1.70 × 101"], ["Transcription", "BP", "1.29", "14", "2.10 × 102", "9.90 × 101"], ["Gamete generation", "BP", "1.13", "6", "4.10 × 102", "9.50 × 101"], ["Chromatin modification", "BP", "0.98", "6", "2.30 × 102", "9.90 × 101"], ["Positive regulation of I-kappaB kinase/NF-kappaB cascade", "BP", "0.95", "4", "3.60 × 102", "9.50 × 101"]], "row_count": 25, "column_count": 6, "numeric_cells": 90, "header_rows": 1, "locator": "section[13]/table-wrap[3]#jcm-09-00134-t004"}}], "gaps": ["asset:data:geo:PXD006889 not downloaded", "asset:data:geo:PXD006889 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, "specific": null, "label": "Kolmogorov-Smirnof test for normality", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Log transformation of iTRAQ ratios resulted in normal distribution as checked by Kolmogorov-Smirnof test for normality."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (Kolmogorov-Smirnof test for normality), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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