Expression profiling of human donor lungs to understand primary graft dysfunction after lung transplantation

Lung transplantation is the treatment of choice for end-stage pulmonary diseases. A limited donor supply has resulted in 4000 patients on the waiting list. Currently, 10-20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15-25% fails due to primary graft dysfunction (PGD). This has resulted in increased efforts to search for alternative donor lungs selection criteria. In this study, we attempt to further our understanding of PGD by observing the changes in gene expression across donor lungs that developed PGD versus those that did not. Our second goal is to use a machine learning tool - support vector machine (SVM), to distinguish unsuitable donor lungs from suitable donor lungs, based on the gene expression data. From our analysis, we have obtained transcripts that were involved in signalling, apoptosis and stress-activated pathways. Results also indicate that metallothionein 3 may prevent lungs from developing PGD. Preliminary classification results for distinguishing suitable and unsuitable lungs for transplantation using a SVM were promising. This is the first such attempt to use human lungs used for transplantation and combine the identification of a molecular signature for PGD, with machine learning methods for donor lung prediction