Bioinformatic analysis as a first step to predict the compatibility of hematopoiesis and immune system genes between humans and pigs.

The shortage of allogeneic donor organs leaves its supply far short of clinical need. There are great expectations on xenotransplantation, especially with pigs' organs. With the genetic modification of donor pigs, the rejection and cross-species transmission issues have now been widely addressed. However, research on the compatibility of genes between humans and pigs was limited. We performed a systematic screening analysis of predicted incompatible genes between humans and pigs, judged by low protein sequence similarities or different predicted protein domain compositions. By combining with gene set enrichment analysis, we screened out several key genes of hematopoiesis and the immune system with possible incompatibilities, which might be important for establishing chimera and xenotransplantation between humans and pigs. There were seven chemokine genes, including CCL1, CCL5, CCL24, CCL25, CCL28, CXCL12, and CXCL16, that exhibited limited similarity between humans and pigs (similarity < 0.8). Among hematopoiesis process-related genes, 15 genes of adhesion molecules, Notch ligands, and cytokine receptors exhibited differences between humans and pigs. In complement and coagulation cascades, 19 genes showed low similarity and 77 genes had different domain compositions between humans and pigs. Our study provides a good reference for further genetic modification of pigs, which might be beneficial for xenotransplantation.