The desire for biomarkers for diagnosis and prognosis of diseases has never been greater. With the availability of genome data and an increased availability of proteome data, the discovery of biomarkers has become increasingly feasible. However, the task is daunting and requires collaborations among researchers working in the fields of transplantation, immunology, genetics, molecular biology, biostatistics, and bioinformatics. With the advancement of high throughput omic techniques such as genomics and proteomics (collectively known as proteogenomics), efforts have been made to develop diagnostic tools from new and to-be discovered biomarkers. Yet biomarker validation, particularly in organ transplantation, remains challenging because of the lack of a true gold standard for diagnostic categories and analytical bottlenecks that face highthroughput data deconvolution. Even though microarray technique is relatively mature, proteomics is still growing with regards to data normalization and analysis methods. Study design, sample selection, and rigorous data analysis are the critical issues for biomarker discovery using highthroughout proteogenomic technologies that combine the use and strengths of both genomics and proteomics. In this review, we look into the current status and latest developments in the field of biomarker discovery using genomics and proteomics related to organ transplantation, with an emphasis on the evolution of proteomic technologies.
KeywordsBiomarker discovery; proteogenomics; genomics; proteomics; microarray; transplantation; acute rejection; peptidomics
A Biomarker: What, why and why not?A biomarker is a gene, protein/peptide or metabolite present in a biological system. It is indicative of a physiological or pathological state that can be recognized or monitored. Monitoring the biomarker thus provides a means for monitoring the disease condition and assists in its diagnosis and prognosis. The additional value of biomarkers lies in the fact that they can correlate with the underlying disease state. Thus, when assessed in biological fluids distant form the actual site of injury, it provides a non-invasive means to follow the underlying disease. A well-known biomarker is serum creatinine, which is a surrogate biomarker for underlying graft injury. Nevertheless, serum creatinine does not meet the criteria for an ideal biomarker for monitoring renal transplant patients as it lacks high specificity (serum creatinine is dependent on muscle mass and hydration status, in the absence of graft injury) and sensitivity (serum creatinine can be elevated with multiple causes of intrinsic and extrinsic graft injury). There is a unmet need of non-invasive which is more specific and sensitive to replace the renal transplant biopsy as the gold-standard. Biomarkers for monitoring graft injury and survival course in the field of solid organ transplantation can be sought with the help of high throughput proteogenomic techniques ( Figure 1).These biomarkers could be a single or a panel of mRNA transcripts,...