Fig. 1

a Single-cell combinatorial indexing and enzymatic conversion (sciEM) workflow in which (i) whole tissue (e.g. brain tissue) is homogenized to dissociates cells. Nuclei from heterogeneous cell-types are isolated and (ii) sorted by Fluorescent Activated Nuclei-Sorting (FANS). (iii) Nuclei membranes are permeabilized, nucleosomes depleted, and molecular tags (tag 1, Tn5 barcode) are attached to genomic DNA via transposome tagmentation. (iv) Nuclei are pooled, (vi) re-sorted by FANS and (vi) unmethylated cytosines are converted to thymine following treatment with TET2 and APOBEC enzymes and Linear amplification. Molecular tags 2, 3 (i5 and i7 barcodes) and sequencing adapters are attached via PCR amplification. (adapted from [9]). b Per cell read processing metric’s. c Cytosine dinucleotides covered as percentage of mapped bases. d, e DNA methylation bias plots for sciEM and sciMET methods respectively for reads mapping to autosome’s and the X-chromosome, with close-up of CHG and CHH DNA methylation (bottom). H = A, C or T