biostudies-literatureLee SYThis work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean governmentThis work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education4https://www.ebi.ac.uk/biostudies/studies/S-EPMC12779986biostudies-literatureUnknown12(1)This study aimed to introduce a synergistic integration platform based on single-cell and proteotranscriptomics for drug repositioning (SIMD) to repurpose breast cancer drug candidates by considering the bidirectional nature of molecular dynamics in protein transcriptomics and tumor heterogeneity at the single-cell level. SMID consists of two core methods: the anti-correlated proteotranscriptome perturbation score (ACPS), which measures the negative correlation between perturbagen-induced expression signatures and multi-omic expression profiles from patient-derived breast cancer samples; and perturbagen repositioning scoring and scRNA-seq data (PPNE), which ranks perturbagens exhibiting high ACPS scores and inverse transcriptomic associations with neoplastic epithelial (NE) cells identifieNPJ breast cancerSIMD: Synergistic integration mutualistic platform based on single-cell and proteotranscriptomics for drug repositioning.PMC12779986RS-2023-NR0772742021R1I1A1A01058604Lee YRLee SYAn JHSong MYfalseSIMD: Synergistic integration mutualistic platform based on single-cell and proteotranscriptomics for drug repositioning.This study aimed to introduce a synergistic integration platform based on single-cell and proteotranscriptomics for drug repositioning (SIMD) to repurpose breast cancer drug candidates by considering the bidirectional nature of molecular dynamics in protein transcriptomics and tumor heterogeneity at the single-cell level. SMID consists of two core methods: the anti-correlated proteotranscriptome perturbation score (ACPS), which measures the negative correlation between perturbagen-induced expression signatures and multi-omic expression profiles from patient-derived breast cancer samples; and perturbagen repositioning scoring and scRNA-seq data (PPNE), which ranks perturbagens exhibiting high ACPS scores and inverse transcriptomic associations with neoplastic epithelial (NE) cells identifie2025-01-01T00:00:00Z2025 Dec2026-06-06T11:22:21.77Z2026-05-29T03:12:31.809ZS-EPMC127799864144422210.1038/s41523-025-00869-x