{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:06:31Z","timestamp":1789549591246,"version":"build-2803163510"},"reference-count":24,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Large language models and automated analytical tools show potential for biomedical text understanding, knowledge integration, and single-cell data interpretation, but interpretations of specific gene regulatory relationships still require empirical grounding. For TF\u2013target relationships, one relevant constraint is whether curated regulatory edges show detectable expression-level statistical evidence in the single-cell data being interpreted, because such evidence may vary across cellular states, conditions, and regulatory mechanisms. We therefore evaluated the statistical visibility of known transcription factor (TF)\u2013target relationships in single-cell expression space to aid the interpretation of regulatory inference and automated-tool outputs. Methods: We performed two complementary analyses: first, testing whether curated TF\u2013target edges showed stronger pair-level associations than matched background gene pairs; and second, assessing whether high-scoring TF\u2013gene pairs corresponded to existing regulatory knowledge and whether their target genes showed pathway coherence. Results: Across four peripheral blood mononuclear cell (PBMC) datasets, four adult tissues, and seven adult cell types, curated TF\u2013target relationships showed weak but reproducible statistical visibility rather than strong separation. For all five association metrics, the mean area under the precision\u2013recall curve (AUPRC) was only slightly above the random-ranking baseline of 0.5. High-scoring pairs were more often supported by curated resources, and their target genes showed context-specific Hallmark pathway coherence. Conclusions: Single-cell expression associations can provide useful but limited statistical clues for TF\u2013target regulation and should be interpreted as complementary rather than definitive regulatory evidence.<\/jats:p>","DOI":"10.3390\/genes17091110","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:10:23Z","timestamp":1789373423000},"page":"1110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Statistical Visibility of Curated TF\u2013Target Regulatory Relationships and Reverse Consistency of Top-Ranked TF\u2013Gene Pairs in Single-Cell Expression Data"],"prefix":"10.3390","volume":"17","author":[{"given":"Wenqing","family":"Feng","sequence":"first","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Zejun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Electrical and Energy Engineering, Shanghai Dianji University, Shanghai 201306, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Zheng","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Chengyu","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9194-2282","authenticated-orcid":false,"given":"Jinlei","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6277-5467","authenticated-orcid":false,"given":"Guoqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Yunqing","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.cell.2018.01.029","article-title":"The Human Transcription Factors","volume":"172","author":"Lambert","year":"2018","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.cell.2015.05.002","article-title":"Highly Parallel Genome-Wide Expression Profiling of Individual Cells Using Nanoliter Droplets","volume":"161","author":"Macosko","year":"2015","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrg3185","article-title":"Insights into the Regulation of Protein Abundance from Proteomic and Transcriptomic Analyses","volume":"13","author":"Vogel","year":"2012","journal-title":"Nat. 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