Enrichments in the transcriptional landscape of the extracellular milieu during transition from pre- to subclinical Sjögren’s syndrome. Gene sets (GSs) enriched at 8 weeks of age delineate activation of the innate immune system coinciding with significant alterations in the targeted tissue’s homeostasis and integrity. Proportions of leading edge (LE) genes shared between GSs defined distance, organization and clustering of the GSs. Dashed lines, separators between major biological themes; annotations in italics, interpretation of transcriptional activity inferred from the LE gene clouds displayed in Figure 4; node color, Markov cluster algorithm (MCL) cluster number. Node shapes: triangles, extracellular milieu (EM)–related; circles, EM-associated; node size, relative to number of detected genes that are members of this GS (reference node = 50 genes). Node label type size, relative to percentage of genes belonging to this GS’s LE (TAGS) (reference node = 75%). Node border: none, alteration of this GS exclusive to C57BL/6.NOD-Aec1Aec2 mice; present, reciprocal trend in C57BL/6 mice. Edge color: degree of overlap in LE genes between the two GSs connected by this edge. ECM, extracellular matrix; Igfr1, insulin-like growth factor receptor 1; Insr, insulin receptor.