ORBIT: Learning Gene Program Co-Activation Structure for Cell-Type-Stratified Pathway Rewiring Analysis in Single-Cell Transcriptomics

arXiv:2605.02142v1 Announce Type: new Abstract: Gene programs co-activate within cells, but existing single-cell methods either treat programs independently or require experimental perturbation data to model their interactions. We introduce ORBIT, a self-supervised transformer that learns asymmetric dependencies among gene programs from observational single-cell RNA-sequencing data alone, quantifying how strongly each program influences every other program. The key mechanism is an intervention-c...