Shannon entropy approach reveals relevant genes in Alzheimer's disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31891941", "kind": "science-record", "revision": 7, "content_hash": "sha256:e739335632d499ce310764674d882f8c59fafdf89de2cea97f7d7e85388f0db0", "created_at": "2026-11-01T15:40:54Z", "updated_at": "2026-11-01T22:01:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Shannon entropy approach reveals relevant genes in Alzheimer's disease.", "doi": "10.1371/journal.pone.0226190", "pmid": "31891941", "authors": ["Alfonso Monaco", "Nicola Amoroso", "Loredana Bellantuono", "Eufemia Lella", "Angela Lombardi", "Anna Monda", "Andrea Tateo", "Roberto Bellotti", "Sabina Tangaro"], "journal": "PloS one", "year": 2019, "abstract": "Alzheimer's disease (AD) is the most common type of dementia and affects millions of people worldwide. Since complex diseases are often the result of combinations of gene interactions, microarray data and gene co-expression analysis can provide tools for addressing complexity. Our study aimed to find groups of interacting genes that are relevant in the development of AD. In this perspective, we implemented a method proposed in a previous work to detect gene communities linked to AD. Our strategy combined co-expression network analysis with the study of Shannon entropy of the betweenness. We analyzed the publicly available GSE1297 dataset, achieved from the GEO database in NCBI, containing hippocampal gene expression of 9 control and 22 AD human subjects. Co-expressed genes were clustered into different communities. Two communities of interest (composed by 72 and 39 genes) were found by calculating the correlation coefficient between communities and clinical features. The detected communities resulted stable, replicated on two independent datasets and mostly enriched in pathways closely associated with neuro-degenative diseases. A comparison between our findings and other module detection techniques showed that the detected communities were more related to AD phenotype. Lastly, the hub genes within the two communities of interest were identified by means of a centrality analysis and a bootstrap procedure. The communities of the hub genes presented even stronger correlation with clinical features. These findings and further explorations on the detected genes could shed light on the genetic aspects related with physiological aspects of Alzheimer's disease.", "claims": [{"id": "claim-method", "statement": "The association, between the communities found in the step 2 of the pipeline and clinical phenotype, was investigated by means of Pearson’s correlation analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31891941", "locator": "sections[7] \"1.5 Correlation analysis of gene modules with clinical phenotype\" paragraph 2", "quote": "The association, between the communities found in the step 2 of the pipeline and clinical phenotype, was investigated by means of Pearson’s correlation analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data underlying the results presented in the study are available from the GEO database in NCBI (Gene Expression Omnibus, https://www.ncbi.nlm.nih.gov/geo/). The data entry number of database is GSE1297.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31891941", "locator": "sections[25] \"Data Availability\" paragraph 2", "quote": "The data underlying the results presented in the study are available from the GEO database in NCBI (Gene Expression Omnibus, https://www.ncbi.nlm.nih.gov/geo/). The data entry number of database is GSE1297."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:31891941"], "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:GSE1297"], "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:GSE1297"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31891941", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0226190", "sha256": "sha256:edf5867195b475d46301742edd6d66cb8cfed064817047dec591e0be3e69fce9", "bytes": 64115, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0226190", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6938408", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE1297", "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=GSE1297", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE1297", "version": null, "note": "The data underlying the results presented in the study are available from the GEO database in NCBI (Gene Expression Omnibus, https://www.ncbi.nlm.nih.gov/geo/). 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p = 0.03", "r = 0.59; p = 0.004"], ["C2", "r = 0.47; p = 0.02", "r = -0.46; p = 0.03"]], "row_count": 3, "column_count": 3, "numeric_cells": 4, "header_rows": 1, "locator": "section[16]/table-wrap[1]#pone.0226190.t001"}}, {"id": "asset:table:pmid:31891941:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:5dac310ea2245e54f5e81489dc1947ed39d935dbb6f832d64e61c0201cc69272", "bytes": 1848, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#pone.0226190.t002", "version": null, "note": "Results of gene set enrichment analysis for C1 community.In the third column overlaps with gene set in the selected MSigDB gene set collection are reported. The fourth column displays the false discovery rate (FDR) analog of hypergeometric p-value after correction for multiple hypothesis testing according to Benjamini and Hochberg [43]. The table shows seven most significant enrichments.", "structure": {"pmcid": "PMC6938408", "section_index": 17, "section_title": "2.4 Gene set enrichment analysis", "row_count": 8, "column_count": 4}, "table": {"label": "Table 2", "caption": "Results of gene set enrichment analysis for C1 community.In the third column overlaps with gene set in the selected MSigDB gene set collection are reported. The fourth column displays the false discovery rate (FDR) analog of hypergeometric p-value after correction for multiple hypothesis testing according to Benjamini and Hochberg [43]. The table shows seven most significant enrichments.", "rows": [["Gene Set Name", "Description", "Genes in overlap", "FDR p-value"], ["BLALOCK ALZHEIMER’S DISEASE DN", "Genes down-regulated in brain from patients with Alzheimer’s disease—Homo sapiens", "32", "1.25 ⋅ 10−28"], ["HALLMARK OXIDATIVE PHOSPHORYLATION", "Genes encoding proteins involved in oxidative phosphorylation—Homo sapiens", "11", "3.87 ⋅ 10−11"], ["GO ELECTRON TRANSPORT CHAIN", "A process in which a series of electron carriers operate together to transfer electrons from donors to any of several different terminal electron acceptors to generate a transmembrane electrochemical gradient—Homo sapiens", "9", "5.24 ⋅ 10−11"], ["GO CELLULAR RESPIRATION", "The enzymatic release of energy from inorganic and organic compounds (especially carbohydrates and fats) which either requires oxygen (aerobic respiration) or does not (anaerobic respiration)—Homo sapiens", "9", "1.24 ⋅ 10−9"], ["GO ORGANONITROGEN COMPOUND METABOLIC P C PROCESS", "The chemical reactions and pathways involving organonitrogen compound—Homo sapiens", "19", "6.23 ⋅ 10−9"], ["KEGG PARKINSONS DISEASE", "Parkinson’s disease—Homo sapiens", "19", "1.38 ⋅ 10−8"], ["BLALOCK ALZHEIMER’S DISEASE UP", "Genes up-regulated in brain from patients with Alzheimer’s disease—Homo sapiens", "18", "1.38 ⋅ 10−8"]], "row_count": 8, "column_count": 4, "numeric_cells": 14, "header_rows": 1, "locator": "section[17]/table-wrap[1]#pone.0226190.t002"}}, {"id": "asset:table:pmid:31891941:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f3281256ea8b9c7bf2411a7fdd8cbef59860f93853a432b78c6c3b69db75be6d", "bytes": 1138, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[2]#pone.0226190.t003", "version": null, "note": "Results of gene set enrichment analysis for C2 community.In the third column the genes in the overlapping gene sets are reported. The fourth column indicates the false discovery rate (FDR) analog of hypergeometric p-value after correction for multiple hypothesis testing according to Benjamini and Hochberg [43]. he table shows the top three significant enrichments.", "structure": {"pmcid": "PMC6938408", "section_index": 17, "section_title": "2.4 Gene set enrichment analysis", "row_count": 4, "column_count": 4}, "table": {"label": "Table 3", "caption": "Results of gene set enrichment analysis for C2 community.In the third column the genes in the overlapping gene sets are reported. The fourth column indicates the false discovery rate (FDR) analog of hypergeometric p-value after correction for multiple hypothesis testing according to Benjamini and Hochberg [43]. he table shows the top three significant enrichments.", "rows": [["Gene Set Name", "Description", "Genes in overlap", "FDR p-value"], ["BLALOCK ALZHEIMER’S DISEASE DN", "Genes down-regulated in brain from patients with Alzheimer’s disease—Homo sapiens", "22", "1.07 ⋅ 10−22"], ["HALLMARK OXIDATIVE PHOSPHORYLATION", "Genes encoding proteins involved in oxidative phosphorylation—Homo sapiens", "9", "1.23 ⋅ 10−10"], ["KIM BIPOLAR DISORDER OLIGODENDROCYTE DENSITY CORR UP", "Genes whose expression significantly and positively correlated with oligodendrocyte density in layer VI of BA9 brain region in patients with bipolar disorder—Homo sapiens", "11", "5.49 ⋅ 10−9"]], "row_count": 4, "column_count": 4, "numeric_cells": 6, "header_rows": 1, "locator": "section[17]/table-wrap[2]#pone.0226190.t003"}}, {"id": "asset:table:pmid:31891941:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:758edd5df2027601d8b697a49c4fd394378a62ca39cc2729cb99802254ef54ce", "bytes": 1125, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[1]#pone.0226190.t004", "version": null, "note": "Summary table of the results obtained through the proposed community detection methods.In the fourth column the number of genes in common with C1 and C2 communities is shown in bold. We reported only significant correlations (p-value < 0.05).", "structure": {"pmcid": "PMC6938408", "section_index": 20, "section_title": "2.7 Identification of gene communities through traditional clustering methods and network reconstruction algorithms", "row_count": 13, "column_count": 6}, "table": {"label": "Table 4", "caption": "Summary table of the results obtained through the proposed community detection methods.In the fourth column the number of genes in common with C1 and C2 communities is shown in bold. We reported only significant correlations (p-value < 0.05).", "rows": [["Method", "Number of communities", "AD-related communities", "Number of genes in AD-related communities", "Correlation coefficient with NFT", "Correlation coefficient with MMSE"], ["Our method", "127", "C1", "71", "0.59", "−0.46"], ["C2", "39", "−0.46", "0.47"], ["WGCNA", "21", "Blue module", "637(87)", "0.43", "−0.43"], ["Affinity propagation", "233", "A1", "31(7)", "0.45", "−0.43"], ["A2", "39(23)", "0.45", "−0.43"], ["Agglomerative clustering", "Between 2 and 30", "None", "", "", ""], ["Fuzzy c-means", "Between 2 and 7", "None", "", "", ""], ["ARACNE", "674", "AR1", "8(2)", "−0.45", "0.44"], ["AR2", "7(5)", "−0.43", "0.43"], ["GENIE3", "675", "G1", "9(3)", "−0.44", "0.44"], ["G2", "7(2)", "−0.44", "0.46"], ["SPACE", "24", "S1", "25(2)", "0.44", "−0.44"]], "row_count": 13, "column_count": 6, "numeric_cells": 38, "header_rows": 1, "locator": "section[20]/table-wrap[1]#pone.0226190.t004"}}], "gaps": ["asset:data:geo:GSE1297 not downloaded", "asset:data:geo:GSE1297 licence not read", "asset:data:geo:GSE29378 not downloaded", "asset:data:geo:GSE29378 licence not read", "asset:data:geo:GSE48350 not downloaded", "asset:data:geo:GSE48350 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "principal component analysis"}}, {"id": "method-2", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}, {"id": "method-3", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "hierarchical clustering"}}, {"id": "method-4", "family": "network_analysis", "specific": "centrality", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "centrality"}}, {"id": "method-5", "family": null, "specific": null, "label": "Pearson’s correlation analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The association, between the communities found in the step 2 of the pipeline and clinical phenotype, was investigated by means of Pearson’s correlation analysis."}}], "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["pca_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pca."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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