TY - JOUR A1 - Li, Siran A1 - Kendall, Jude A1 - Park, Sarah A1 - Wang, Zihua A1 - Alexander, Joan A1 - Moffitt, Andrea A1 - Ranade, Nissim A1 - Danyko, Cassidy A1 - Gegenhuber, Bruno A1 - Fischer, Stephan A1 - Robinson, Brian D. A1 - Lepor, Herbert A1 - Tollkuhn, Jessica A1 - Gillis, Jesse A1 - Brouzes, Eric A1 - Krasnitz, Alex A1 - Levy, Dan A1 - Wigler, Michael T1 - Copolymerization of single-cell nucleic acids into balls of acrylamide gel Y1 - 2020/01/01 JF - Genome Research JO - Genome Research SP - 49 EP - 61 DO - 10.1101/gr.253047.119 VL - 30 IS - 1 UR - http://genome.cshlp.org/content/30/1/49.abstract N2 - We show the use of 5′-Acrydite oligonucleotides to copolymerize single-cell DNA or RNA into balls of acrylamide gel (BAGs). Combining this step with split-and-pool techniques for creating barcodes yields a method with advantages in cost and scalability, depth of coverage, ease of operation, minimal cross-contamination, and efficient use of samples. We perform DNA copy number profiling on mixtures of cell lines, nuclei from frozen prostate tumors, and biopsy washes. As applied to RNA, the method has high capture efficiency of transcripts and sufficient consistency to clearly distinguish the expression patterns of cell lines and individual nuclei from neurons dissected from the mouse brain. By using varietal tags (UMIs) to achieve sequence error correction, we show extremely low levels of cross-contamination by tracking source-specific SNVs. The method is readily modifiable, and we will discuss its adaptability and diverse applications. ER -