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Recent advances in single-molecule imaging in living cells allow quantitative and system-wide descriptions of gene expression and regulation with single molecule sensitivity.It was found that low probability events of single molecules can have important biological consequences, such as the change of a cellular phenotype.This has everything to do with the fact that DNA are single molecules in individual cells.Meanwhile, recent advances in high throughput DNA sequencing have allowed sequencing the genome and transcriptome of a single human cell.The combination of single molecule and single cell imaging and sequencing offers exciting possibilities for biology.