Combinatorial perturbation sequencing on single cells using microwell-based droplet random pairing

Combinatorial drug therapy reduces drug resistance and disease relapse, but informed drug combinations are lacking due to the large scale of possible combinations and the relatively simple phenotyping strategies. Here we report combinatorial perturbation sequencing (CP-seq) on single cells using microwell-base droplet random pairing. CP-seq uses oligonucleotides to barcode drugs, encapsulates drugs and cells in separate droplets, and pairs cell droplets with two drug droplets randomly on a microwell array chip to complete combinatorial drug treatment and barcode-tagging on cells. Here, the MCF-7 cell line was used as the test sample. The scRNA-seq data of MCF-7 cells treated with corona, single drugs, and combinations of drugs were stored in the repository.