Fig. 4

Identification and characterization of clones, meta-clones, and k-mers associated with rheumatoid arthritis. a CDR3 amino acid sequences of the clones showing a significantly different abundance in rheumatoid arthritis compared to healthy controls (FDR < 0.05). b On the left side, the expression of the two clones showing the strongest association with rheumatoid arthritis is shown. On the right side, the clone expression is plotted against the standardized clone detection rate, indicating that the associations detected are not influenced by the sampling bias. Abbreviations: CPM, counts per million; P, p-value. c CDR3 amino acid sequence similarity networks and amino acid motif of the IGL and IGK clones associated with rheumatoid arthritis. In the similarity networks, each clone is represented as a node and edges connect clones differing by at most one amino acid in the CDR3 sequence. The node size is proportional to its number of similarity connections with other clones. The p-value shown for each chain indicates the probability of observing the indicated similarity by chance. Abbreviations: P, p-value. d Biochemical profile of the clones significantly associated with rheumatoid arthritis. For each chain, the enrichment of the associated clones in each biochemical feature is represented by a circle. The circle is colored according to the degree of biochemical enrichment (i.e., blue) or depletion (i.e., red) compared to a random repertoire from the same chain. The size of the circle is proportional to the statistical significance of the enrichment in each biochemical feature. Abbreviations: BES, Biochemical Enrichment Score. e Overview of the meta-clone analytical strategy used here to identify groups of highly similar clones associated with disease conditions. Abbreviations: CPM, counts per million. f CDR3 amino acid sequence similarity network and amino acid motif of the meta-clone 9 from TRG chain that showed a significant association with the clinical response to TNFi therapy. The network parameters are described in (c). g On the left side, expression levels of the meta-clone 9 from TRG in responder and non-responder patients to TNFi therapy. On the right side, the expression of meta-clone 9 is plotted against the standardized meta-clone detection rate. Abbreviations: CPM, counts per million; P, p-value. h K-mers showing a significantly different abundance in rheumatoid arthritis compared to healthy controls (FDR < 0.05). i On the left side, the expression level of the two k-mers showing the strongest association with rheumatoid arthritis is shown. On the right side, the k-mer expression is plotted against the standardized k-mer detection rate. Abbreviations: CPM, counts per million; P, p-value. j Pairwise dissimilarity matrix among IGK k-mers significantly associated with RA (FDR < 0.05). K-mers over- and under-represented in rheumatoid arthritis are represented in dark and light blue, respectively. The dissimilarity index was computed using the Levenshtein distance measure so that the higher the Levenshtein distance, the higher the dissimilarity index between two k-mer sequences. Abbreviations: RA, rheumatoid arthritis. k Biochemical profile of the k-mers significantly associated with rheumatoid arthritis. The graphical parameters are described in (d)