BackgroundAs a first-line treatment for acute ischemic stroke (AIS), tenecteplase (TNK) can cause adverse effects, such as depression, in AIS patients.ObjectiveThis study aims to elucidate the TNK target-related pathogenic mechanisms underlying major depressive disorder (MDD) in AIS patients.MethodsBy analyzing six public peripheral blood bulk datasets from AIS and MDD patients using integrative bioinformatics methods (limma, non-negative matrix factorization (NMF), and machine learning), we ide