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Genome Med. 2014 Apr 28;6(4):31. doi: 10.1186/gm548. eCollection 2014.

Fourth-generation sequencing in the cell and the clinic.

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Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Solna Se-171 21, Stockholm, Sweden.


Nearly 40 years ago, DNA was sequenced for the first time. Since then, DNA sequencing has undergone continuous development, passing through three generations of sequencing technology. We are now entering the beginning of a new phase of genomic analysis in which massively parallel sequencing is performed directly in the cell. Two methods have recently been described for in situ RNA sequencing, one targeted and one untargeted, that rely on ligation chemistry. This fourth generation of sequencing technology opens up prospects for transcriptomic analysis, biomarker validation, diagnosis and patient stratification for cancer treatment.

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