“…These included the highly variable and abundant genes including chemokine family Ccl5, Ccl4, Ccl3, Ccl2 as well as IL1b and TNFa. While the scRNA-seq can be in principle treated as time-series data (e.g., across the replicates from individual mice) [34], our current understanding of TLR signalling suggest that due to endotoxin resistance and desensitisation [56][57][58], the regulatory network, and thus model structures and parameters, are time-varying rather than stationary [59]. We therefore treated each data time-point (and replicate) separately, which also allowed more efficient implementation to fit 1,507 mouse, and 1,079 orthologue conditions.…”