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A computational pipeline for processing single-cell bisulfite sequencing data

Uzun Y 1,2,3, Yu W4,5, Chen C4, Wu H 6,7 and Tan K ,4,5,6,7 1 Department of Pediatrics, Pennsylvania State University, College of Medicine, Hershey, PA, USA 2 Department of Biochemistry and Molecular Biology, Pennsylvania State University, College of Medicine, Hershey, PA, USA 3 Four Diamonds Pediatric Cancer Research Center, Pennsylvania State University, College of Medicine, Hershey, PA, USA 4 Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Philadelphia, PA, USA 5 Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, USA 6 Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA 7 Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA , USA


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Single-cell bisulfite sequencing technologies enable profiling of the methylome at high resolution, providing the basis for dissecting the heterogeneity and dynamics of DNA methylation in complex tissues and over time. Despite the rapid increase in the number of experimental protocols for methylome sequencing, analytical tools designed specifically for single-cell data are lacking. To address this methodology gap we developed SINBAD, a framework for standardized processing, quality assessment and analysis of single-cell bisulfite sequencing datasets. As a flexible platform, SINBAD consists of interoperable components that perform read pre-processing, alignment, methylation calling, multivariate analysis, and gene signature profiling for single-cell methylome data.

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