MIRCID: Inferred Hub-miRNAs Drive Cross-Task Improvements in Drug Mechanistic Modeling

MIRCID, a framework comparing gene expression with inferred transcription factor activity and miRNA expression, infers 414 pan-cancer hub miRNAs from 977 L1000 landmark genes with a Pearson correlation coefficient of 87.72%, according to the arXiv paper. The framework's 1,298-output variant outperformed SiCmiR on the full-miRNA task, 71.21% versus 67.30%, and miRNA augmentation produced more consistent gains than TF activity in the evaluated comparisons. The authors report that inferred HubmiRs offer a biologically informed recoding of transcriptomic data for perturbational drug modeling, while recovery of measured perturbational miRNA responses requires further validation.

arXiv:2609.21280v1 Announce Type: new Abstract: Drug mechanism-of-action MoA modeling commonly relies on perturbational transcriptomes, but matched microRNA miRNA measurements are often unavailable. Inferred regulatory features offer a scalable way to reuse these data. Here, we present MIRCID, a framework comparing gene expression with inferred transcription factor TF activity and miRNA expression across pathway classification and similarity-based MoA retrieval. HubmiRNet infers 414 pan-cancer hub miRNAs HubmiRs from 977 L1000 landmark genes, achieving a Pearson correlation coefficient of 87.72\%; its 1,298-output variant also outperformed SiCmiR on the full-miRNA task 71.21\% versus 67.30\% . In the evaluated comparisons, miRNA augmentation provided more consistent gains than TF activity. Generic embedding controls showed model-dependent utility, while complementarity analyses identified a distinct, partially linearly recoverable representation that retained gene-derived structure. Illustrative rescue cases linked improved classification to biologically plausible miRNA patterns in samples with weak transcriptional signatures. These findings support inferred HubmiRs as a biologically informed recoding of transcriptomic data for perturbational drug modeling, while leaving recovery of measured perturbational miRNA responses to further validation.