Supplementary Materials

Landmarks of human embryonic development inscribed in somatic mutations

Sara Bizzotto, Yanmei Dou, Javier Ganz, Ryan N. Doan, Minseok Kwon, Craig L. Bohrson, Sonia N. Kim, Taejeong Bae, Alexej Abyzov, NIMH Brain Somatic Mosaicism Network, Peter J. Park, Christopher A. Walsh

Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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  • Materials and Methods
  • Supplementary Text: List of Members of the Brain Somatic Mosaicism Network
  • Figs. S1 to S10
  • Captions for Tables S1 to S10
  • References
Table S1
Bulk DNA samples obtained from multiple organs and used for WGS and targeted amplicon sequencing.
Table S2
(A) sSNVs called in WGS data from 5 tissue samples from individual UMB1465. (B) Variants filtered using single cell WGS data. (C) AAFs and allele counts of called sSNVs in the 5 samples sequenced. Average AAFs and validation status in single cell WGS are also reported for each variant. (D) Expected vs. observed value of AAFs of different cell-generation sSNVs from different clades. (E to F) MosaicForecast variant calling in 3 brain bulk sample WGS data from individuals UMB4638 and UMB4643.
Table S3
Functional annotation of UMB1465 sSNVs called in 5-sample WGS data. Exonic variants are reported in a separate sheet.
Table S4
(A) Validation of 229 sSNVs from UMB1465 targeted by amplicon sequencing. For each variant, presence or absence in different embryonic germ-layers and CNS regions is indicated, together with average AAF, presence in single cell WGS data, and average forebrain AAF. (B) Experimental evaluation of each variant targeted across 94 bulk samples as well as in negative controls. (C) Organ specific sSNVs validated by targeted sequencing.
Table S5
(A) Genotype of all sSNVs representing lineage markers of postzygotic clones in WGS from 20 single neurons for individual UMB1465. (B to C) Genotype of sSNVs representing lineage markers of postzygotic clones in WGS data from 10 single cells each for individuals UMB4638 and UMB4643.
Table S6
Estimation of lineage contributions of first-cell-generation clones among 55 individuals based on previously published brain WGS data.
Table S7
(A) Average AAFs of all validated sSNVs across different organs. (B) All validated sSNVs ordered by whole-body AAFs (from highest to lowest).
Table S8
Presence/absence across all bulk samples of 19 CNS-specific sSNVs. NA corrections and exact depth and AAFs are reported in separated sheets.
Table S9
(A to B) Batches, sequencing lanes and cortex sections of all 1228 cortical single cells submitted to targeted-sequencing. (C to F) Genotype posteriors of 37 sSNVs in 791 single cortical cells and clade assignment of these cells.
Table S10
(A to B) snRNA-seq and snATAC-seq meta data, UMAP information, variant loci with non-zero coverage, lineage clade, cell generation, and genotype for the variant locus. (C) Differentially expressed genes for each snRNA-seq cell type cluster calculated comparing each separate group to the rest of the cells. (D) Closest genes to differentially accessible peaks for each snATAC-seq cell type cluster. (E) Number of cells subdivided by cell type in snRNA-seq and snATAC-seq, where each of the 297 sSNV locus had non-zero coverage, and corresponding number of mutant cells.
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