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Despite ongoing research, the molecular mechanisms driving this progression remain poorly understood. In this study, we aimed to uncover key regulatory factors involved in MM progression by integrating single-cell RNA sequencing (scRNA-seq) data with curated a priori biological knowledge of MM. To this end, we first integrated a priori knowledge from databases in a synthetic gene network map to play the role of an MM-related backbone to project findings from scRNA analysis on CD138+ Plasma Cells. This was followed by stage-specific regulatory network construction and analysis using Integrated Value of Influence (IVI) metrics to identify the most influential genes across disease stages. Our findings revealed GSK3B, RELA, CDKN1A, and PCK2 as central regulators shared across multiple stages of the disease. Notably, several of these genes had not previously been included in established MM gene sets, highlighting them as prime candidates for biomarkers and drug targets.<\/jats:p>","DOI":"10.3390\/ijms27020793","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T18:40:09Z","timestamp":1768329609000},"page":"793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Network Analysis of Single-Cell RNA Findings and a Priori Knowledge Highlights Gene Regulators in Multiple Myeloma Progression"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7229-3617","authenticated-orcid":false,"given":"Grigoris","family":"Georgiou","sequence":"first","affiliation":[{"name":"Bioinformatics Department, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, 2370 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8950-4077","authenticated-orcid":false,"given":"Margarita","family":"Zachariou","sequence":"additional","affiliation":[{"name":"Bioinformatics Department, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, 2370 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2470-3363","authenticated-orcid":false,"given":"George M.","family":"Spyrou","sequence":"additional","affiliation":[{"name":"Bioinformatics Department, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, 2370 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2323890","DOI":"10.1080\/16078454.2024.2323890","article-title":"Hub genes and associated drugs for multiple myeloma with 1q21+: Identified by bioinformatic analysis","volume":"29","author":"Xu","year":"2024","journal-title":"Hematology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1080\/16078454.2021.2003980","article-title":"Identification of key miRNA signature and pathways involved in multiple myeloma by integrated bioinformatics analysis","volume":"26","author":"Dong","year":"2021","journal-title":"Hematology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1177\/1078155220934162","article-title":"Age demographics of subjects enrolled in interventional phase 3 multiple myeloma clinical trials","volume":"26","author":"Borad","year":"2020","journal-title":"J. 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