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However, the specific regulatory pathways driving this shared pathophysiology have remained elusive, as prior studies have been limited by single-level data. To dissect this common pathobiology, we implemented a synergistic computational framework, integrating bulk transcriptomics with single-cell data. Through a multi-tiered analysis pipeline employing differential expression, weighted gene co-expression networks, and machine learning\u2013based feature selection, we pinpointed a core molecular signature of 31 shared hub genes. Among these, four core candidates\u2014GPR15, PTGDR2, FCER1A, and MAL\u2014were significantly downregulated, a finding robustly associated with impaired CD8+ T cell infiltration. Delving deeper into the regulatory architecture using a modified weighted out-degree centrality algorithm, we constructed an integrated transcription factor\u2013microRNA\u2013target network. Network analysis revealed upregulation of p53 and downregulation of miR-3619-5p as possible drivers of immune dysfunction. Finally, E-4031 was identified through molecular simulation as a potential therapeutic agent targeting all four core genes. These findings uncover a shared regulatory axis involving immune suppression and transcriptional disruption, and provide promising diagnostic and therapeutic targets for CRC and COVID-19.<\/jats:p>","DOI":"10.1093\/bib\/bbag065","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:41:35Z","timestamp":1771418495000},"source":"Crossref","is-referenced-by-count":1,"title":["Revealing shared molecular markers and mechanisms in colorectal cancer and COVID-19 through bioinformatics and machine learning"],"prefix":"10.1093","volume":"27","author":[{"given":"Hairui","family":"Wang","sequence":"first","affiliation":[{"name":"School of Science, China University of Geosciences , Xueyuan Road 29, Haidian District, Beijing 100083 ,","place":["China"]},{"name":"Multi-disciplinary Research Division, Institute of High Energy Physics Chinese Academy of Sciences , 19B Yuquan Road, Shijingshan District, Beijing 100049 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