BCR and TCR repertoire diversity measures
BCR/TCR repertoires were extracted from bulk RNA sequencing data using the MiXCR toolIsotypes (IgG, IgA, IgM, IgD, IgE) for the BCR heavy chain were determined based on the constant region (C region) information, whenever present. In particular, the isotype could not be determined in 23% of the IGH clones in NeoALTTO and 19% in CALGB 40601. For the remaining IGH clones, isotype proportions are shown in Supplementary Fig The following BCR and TCR repertoire metrics were calculated: read counts, number of clones, length of the CDR3, top and second top clone proportions. Diversity indices including Gini index, Gini-Simpson index and species evenness were calculated as well. Those measures were computed for each BCR/TCR chain separately, as well as “global” measures considering all clones belonging to either BCR or TCR (Supplementary data Evenness and second top clone were calculated if at least two different clones were present. Gini and Gini-Simpson indices were calculated when at least 1 clone was present, assigning a value of 0 when only one clone was present. CDR3 length was calculated when at least one clone was present. We defined BCR/TCR metrics (illustrative examples in Supplementary Fig. From the MiXCR output, we calculated these measures for each chain forming BCR and TCR (IGH/K/L and TRA/B/D/G, respectively), as well as global values from the total reads mapping to BCR and TCR, thus representing the whole BCR and TCR repertoires.For univariable and multivariable analyses, the Shapiro-Francia test was used to evaluate normality of the BCR and TCR measures separately in NeoALTTO and CALGB 40601. In details, when a BCR/TCR feature had no values equal to 0 in the cohort, a log transformation (log