Fig. 1: Study design, proof of concept in positive cohort and overview of negative cohort.

Shown are (a) the study design schema, along with the wet bench and bioinformatics workflows with the tools used. Information about the positive (N = 17) and negative (N = 51) samples are in Supplementary Fig. 1a and Supplementary Data 2. Samples used for optimization (N = 59) include two samples with SMN1 carrier status and 57 samples set with previously confirmed methylation profiles, as explained in the main text. b counts of CNVs and SVs for each method in each filtering step of the “funnel-down” approach. c aggregate methylation profile of SMA –heatmap of base methylation modification (%) within the SMN1 chr5:70239954-70249165 region (left panel) and IGV methylation view in SMN1 (right panel) for SMA positive (OXN-007, OXN-008, OXN-010, OXN-068, OXN-069), SMA carrier (OXN-070, OXN-071) and SMA negative samples (OXN-012, OXN-021). d the gender and demography and (e) the most prevalent primary clinical symptom in the “Negative Cohort”. Source data are provided as a Source Data file.