Multiple subclones coexist within FL tumor populations. (A) Malignant B cells in LPM011 segregate into 5 subclones (shown in tSNE space). (B) Relative proportions of tumor subclones is shown for LPM011 along with the 5 other FLs. Largest subclone dominates more than 50% of the tumor population in each analyzed FL. (C) ScRNA-Seq data recapitulates exome-Seq data: genes differentially expressed in largest subclone of each sample (clone 0) harbor somatic mutations with higher allele frequencies compared with the other genes. For each subclone and FL, the top 1 most differentially expressed, mutated gene was included in this comparison. (D) 21 canonical pathways had a strong differential activity across the subclones of at least 1 FL (analysis of variance: P < 1E-16). In 5 of 6 FLs, these pathways distinguish 1 or 2 smaller outlier subclones (red edges in dendrograms), with activity patterns diverging strongly from the corresponding sample’s other subclones, including the largest 1 (clone 0).