{"doi":"10.1371/journal.pone.0220742","title":"Exploring induced pluripotency in human fibroblasts via construction, validation, and application of a gene regulatory network","abstract":null,"journal":"PLOS ONE","year":2019,"id":636844,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":452589,"name":"Yi‐Kuo Yu","orcid":"0000-0002-6213-7665","position":1,"is_corresponding":false},{"id":1653254,"name":"Mehdi B. Hamaneh","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Exploring induced pluripotency in human fibroblasts via construction, validation, and application of a gene regulatory network","abstract":"Reprogramming of somatic cells to induced pluripotent stem cells, by overexpressing certain factors referred to as the reprogramming factors, can revolutionize regenerative medicine. To provide a coherent description of induced pluripotency from the gene regulation perspective, we use 35 microarray datasets to construct a reprogramming gene regulatory network. Comprising 276 nodes and 4471 links, the resulting network is, to the best of our knowledge, the largest gene regulatory network constructed for human fibroblast reprogramming and it is the only one built using a large number of experimental datasets. To build the network, a model that relates the expression profiles of the initial (fibroblast) and final (induced pluripotent stem cell) states is proposed and the model parameters (link strengths) are fitted using the experimental data. Twenty nine additional experimental datasets are collectively used to test the model/network, and good agreement between experimental and predicted gene expression profiles is found. We show that the model in conjunction with the constructed network can make useful predictions. For example, we demonstrate that our approach can incorporate the effect of reprogramming factor stoichiometry and that its predictions are consistent with the experimentally observed trends in reprogramming efficiency when the stoichiometric ratios vary. Using our model/network, we also suggest new (not used in training of the model) candidate sets of reprogramming factors, many of which have already been experimentally verified. These results suggest our model/network can potentially be used in devising new recipes for induced pluripotency with higher efficiencies. Additionally, we classify the links of the network into three classes of different importance, prioritizing them for experimental verification. We show that many of the links in the top ranked class are experimentally known to be important in reprogramming. Finally, comparing with other methods, we show that using our model is advantageous.","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31374103","pmcid":"PMC6677386","openalex_id":"https://openalex.org/W2966780451","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"ZIA LM092404","title":null},{"funder_name":"National Institutes of Health","grant_id":"1ZIALM092404-12","title":"Robust Accurate Identification of peptides from tandem mass spectrometry data"}],"total_grants":2,"fwci":0.0759,"citation_percentile":0.42589793,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2025,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0220742&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0220742&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0220742","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0220742","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31374103","host_type":"repository"},{"url":"https://doaj.org/article/7b6b08bef07f4b4e8660987851320f28","host_type":"repository"},{"url":"https://figshare.com/articles/Exploring_induced_pluripotency_in_human_fibroblasts_via_construction_validation_and_application_of_a_gene_regulatory_network/9231587","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6677386","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6677386","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6677386?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pone.0220742","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pone.0220742","host_type":""}],"fields_of_study":["Pluripotent Stem Cells Research","CRISPR and Genetic Engineering","Gene Regulatory Network Analysis","0301 basic medicine","0303 health sciences","03 medical and health sciences","Cellular Reprogramming","Fibroblasts","Gene Expression Profiling","Gene Expression Regulation","Gene Regulatory Networks","Humans","Induced Pluripotent Stem Cells"],"mesh_terms":["Fibroblasts","Gene Expression Regulation","Humans","Gene Expression Profiling","Gene Regulatory Networks","Induced Pluripotent Stem Cells","Cellular Reprogramming"],"keywords":["Reprogramming","Gene regulatory network","Induced pluripotent stem cell","Computational biology","Biology","Biological network","Network model","Computer science","Gene expression","Gene","Genetics","Embryonic stem cell","Data mining","Science","Gene Expression Profiling","Q","Induced Pluripotent Stem Cells","R","Fibroblasts","Cellular Reprogramming","Gene Expression Regulation","Medicine","Humans","Gene Regulatory Networks","Research Article"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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