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Existing reviews catalog methods thoroughly but rarely formalize how negative or discordant wet\u2010laboratory results should feed back into computational prioritization, so the iterative refinement that lncRNA biology requires is left implicit. We set out the Hypothesis\u2010Driven Loop, which recasts lncRNA functional analysis as a cycle of three phases: Generation (computational priors), Testing (wet validation), and Refinement (integration that updates the priors for the next round). The cycle itself is Platt's strong inference; what is specific to lncRNAs are the constraints that reshape it\u2014a detectability floor that gates every functional claim, an orders\u2010of\u2010magnitude asymmetry between prediction and validation throughput, and the ambiguity of what a locus\u2010level perturbation actually removes\u2014together with the deliverable each phase must produce. We map existing tools onto the appropriate phase; give a one\u2010page Loop worksheet with an odds\u2010form procedure for updating priors and pre\u2010declared stopping boundaries; and specify how a negative result is triaged as technical or biological before it may revise a hypothesis. Three worked programs\u2014BRIC\u2010seq and the SLiTs paradigm from our laboratory, and HOTAIR, assembled by independent groups from results that disagreed\u2014show that Loops can be entered at different phases and that closure can be a community\u2010level property. The claim is deliberately narrow: iterative dry\u2013wet coupling, recorded so that it can be audited, is one discipline that may help narrow the annotation\u2013function gap.<\/jats:p>","DOI":"10.1002\/wrna.70059","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:40:13Z","timestamp":1790991613000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Hypothesis\u2010Driven Loop: An Integrated Dry\u2013Wet Framework for Long Noncoding\n                    <scp>RNA<\/scp>\n                    Functional Analysis"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6390-4136","authenticated-orcid":false,"given":"Hidenori","family":"Tani","sequence":"first","affiliation":[{"name":"Yokohama University of Pharmacy  Yokohama 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